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EOICAL  BOOKS 

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afUr  addition  of  salt 


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corpuscular  envelopes 
ruptured. 


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">  2.  The  colourless  corpuscles  of  human  blood,  x  1000.  a,  eosinophile  cells  ; 
b.  finely  granular  oxyphile  cells  ;  c,  hyaline  cells  ;  d,  lymphocyte ; 
e,  polymorphonuclear  neutrophile  cells  (Kanthack  and  Hardy).  The 
magnification  is  much  greater  than  in  1. 

3.   Cover-glasa  preparation  of  spinal  cord  of  ox,    x  250. 
iSlfiined  unth  mtthyhne  blue). 
Dendritic  proeettet 


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Capillary 


4.  Potassium  in  a,  frog's  erythrocyte  (black) ; 
b,  nerve  (black) ;  c,  striped  muscle  (black) ; 
d,  cartilage  cells  (yellow)  (Macalluiii). 


F}-ontispiecf 


MANUAL  OF  PHYSIOLOGY 

IMitb  ipractical  £ycrci6e0 


BY 

G.  N.  STEWART,  M.A.,  D.Sc,  M.D.Edin.,  D.P.H.Camb. 

PROFKSSOR    OP    EXPERIMENTAL    MEDICINE    IN    WESTERN    RESERVE    UNIVERSITY,    CLINICAL 

PHYSIOLOGIST    TO     LAKESIDE     HOSPITAL,     CLEVELAND;     FORMERLY     PROFESSOR     OF 

PHYSIOLOGY  IN  THE  UNIVERSITY  OF  CHICAGO;    PROFESSOR  OF  PHYSIOLOGY  IN 

THE  WESTERN  RESERVE  UNIVERSITY  ;  GEORGE  HENRY  LEWES  STUDENT; 

EXAMINER    IN    PHYSIOLOGY    IN   THE    UNIVERSITY    OF   AnF.RDEEN  ; 

SENIOR    DEMONSTRATOR    OF   PHYSIOLOGY   IN   THE   OWliNS 

COLLEGE,      VICTORIA      UNIVERSITY,      ETC 


WITH   COLOURED    PLATE   AND   467   OTHER    ILLUSTRATIONS 


SEVENTH    EDITION 


NEW    YORK 
WILLIAM     WOOD     6c     COMPANY 

MDCCCCXIV 


First  Edition,  September,  1896 
Second  Edition,  October,  1898 
Third  Edition,  August,  1899 
Fourth  Edition,  September,  igoo 
Reprinted,  September,  1901  ;  July,  1903 ; 

and  July,  1904 
Fifth  Edition,  November,  1905 
Sixth  Edition,  September,  1910 
Seventh  Ediiion,  September,  19 14 


(d  T-i^ 


\    J    \    \ 


Printed  in  E»i;land. 


PREFACE  TO  THE  SEVENTH   EDITION 

In  the  present  edition  the  book  has  been  extensively  revised.  The 
rapid  progress  of  biochemistry  has  rendered  it  necessar\'  to  enlarge 
greatly  and  practically  to  rewrite  th-^  chapter  on  Metabolism. 
Many  changes  and  additions  have  also  been  made  in  the  chapters 
on  Circulation,  Respiration,  Digestion,  Absorption,  and  Internal 
Secretion.  The  blood-gases  are  considered  in  much  greater  detail 
than  in  the  last  edition,  and  more  space  is  devoted  to  the  general 
phenomena  of  the  action  of  enzymes.  The  newer  work  on  the 
relation  of  the  heat  production  and  the  chemical  changes  in  muscle 
to  the  contraction  has  been  taken  account  of.  The  chapters  on 
the  Nervous  System  have  been  brought  up  to  date.  The  arrange- 
ment of  the  book  has  been  improved,  it  is  hoped,  by  breaking  the 
longer  chapters  up  into  sections,  and  increasing  the  number  of 
chapters.  Many  new  illustrations  have  been  added,  and  many  of 
the  old  ones  redrawn. 


G.  N.  STEWART. 


Cleveland, 

August,  1914. 


Digitized  by  tine  Internet  Arciiive 

in  2010  witii  funding  from 
Columbia  University  Libraries 


http://www.archive.org/details/manualofphysiolo06stew 


EXTRACT  FROM  THE  PREFACE  TO 
THE  FIRST  EDITION 

In  this  book  an  attempt  has  been  made  to  interweave  formal  ex- 
position with  practical  work,  according  to  a  programme  which  I 
have  followed  for  some  time  past  in  teaching  Physiology  to  medical 
students  on  the  other  side  of  the  Atlantic,  and  which  has,  it  is 
believed,  proved  to  be  well  adapted  to  their  needs  and  opportunities. 
It  ought,  however,  to  be  explained  thit,  for  various  reasons,  a 
somewhat  wider  range  of  experiment  is  open  to  the  student  in 
America  than  in  this  country.  But  as  nobody  will  use  this  book 
except  in  a  regular  laboratory  and  under  responsible  guidance,  it 
has  not  been  thought  necessary  to  mark  in  any  special  manner  the 
parts  of  the  exercises  which  the  English  student  must  do  by  proxy 
(that  is,  learn  from  demonstrations),  and  the  parts  he  ought  to 
perform  for  himself. 

An  arrangement  of  the  exercises  with  reference  to  the  systematic 
course  has  this  advantage — that  by  a  little  care  it  is  possible  to 
secure  that  practical  work  on  a  given  subject  shall  actually  be  going 
on  at  the  time  it  is  being  expounded  in  the  lectures.  Cross-refer- 
ence from  lecture-room  to  laboratory,  and  from  laboratory  to 
lecture-room,  from  the  detailed  discussion  of  the  relations  of  a 
phenomenon  to  the  li\ing  fact  itself,  is  thus  rendered  easy,  natural, 
and  fruitful. 

As  some  teachers  ma}'  wish  to  know  how  a  course  such  as  that 
described  in  the  Practical  Exercises  may  be  conducted  for  a  fairly 
large  class,  a  few  words  on  the  method  we  have  followed  may  not 
be  out  of  place.  It  is  obvious  that  many  of  the  exercises  require 
n.ore  than  one  pcroon  for  th'ir  performance;  and  it  may  be  said 

vii 


X  CONTENTS 

PAGE 

Section  V. — Lymph  and  Chyle              -            -            -             -  57 

Lymph  -  -  -  -  -  -  -57 

Chyle 58 

Section  VI. — Functions  of  Blood  and  Lymph            -             -  59 
Phagocytosis  -             -             -             -             -             -             "59 

Diapedesis       -  -  -  -  -  -  -61 

CHAPTER  III. 

THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH. 

Section  I. — Preliminary  Anatomical  and  Physical  Data  -  80 

Physiological  anatomy  of  the  vascular  system             -             -  81 

Flow  of  a  liquid  through  tubes            -              -              -              -  83 

Section   II. — The   Beat   of  the   Heart   in   its   Physical   or 

Mechanical  Relations     -             -             -             -             -  85 

Events  in  the  cardiac  cycle    -             -             -             -             -  85 

The  sounds  of  the  heart         -             -             -             -             -  88 

The  cardiac  impulse    -             -             -             -             -             -  90 

Endocardiac  pressure               -             -             -             -             -  92 

The  ventricular  pressure-curve            -             -             -             -  94 

The  auricular  and  venous  pressure-curve        -             -             -  98 

Section  III.— Physical  or  Mechanical  Phenomena  of  the 

Circulation  in  the  Bloodvessels          .            -            -  loi 
The  arterial  pulse        -             -             -             -             -             -loi 

Arterial  blood-pressure             .             .             -             _             _  109 

Measurement  of  the  blood-pressure  in  man     -             -             -  113 
Velocity  of  the  blood  -             -             -             -             -             -117 

Measurement  of  velocity  of  blood       -              -              -             -  120 

The  volume-pulse         _-_---  127 

The  circulation  in  the  capillaries        -              -              -             -  129 

The  circulation  in  the  veins  -              -              -              -              -  132 

The  circulation-time    ------  135 

Work  and  output  of  heart      -              -              -             -              -  I39 

Section  IV. — The  Heart-Beat  in  its  Physiological  Rela- 
tions --___--  140 
Intrinsic  nerves  of  the  heart  -----  141 
Cause  of  the  heart-beat  -----  141 
Conduction  and  co-ordination  in  heart  -  -  .  j^g 
Auriculo-ventricular  bundle  -----  147 
Fibrillary  contractions  -  -  -  -  -  151 
Chemical  conditions  of  heart-beat  -  -  -  -  152 
Resuscitation  of  the  heart  -  -  -  -  -  ^53 
Refractory  period  of  heart     -----  155 


173 

177 


CONTENTS  xi 

FACE 

Section  V. — The  Nervous  Regulation  of  the  Heart  (Ex- 
trinsic Venous  Mechanism  of  the  Heart)      -  -  156 
Action  of  poisons  on  the  heart            -             -             -  -  164 
Normal  excitation  of  cardiac  nervous  mechanism     -  -  166 

Section  VI. — The  Nervous  Regulation  of  the  Bloodvessels 

(Vaso-Motor  Nerves)        -             -  -  -  -171 

The  chief  vaso-motor  nerves  -             -  -  _ 

Vaso-dilator  fibres       -             -             .  .  _ 

Course  of  the  vaso-motor  nerves         -  -  -  -     179 

Vaso-motor  centres     -             -             -  -  -  -180 

Vaso-motor  reflexes    -             -             -  -  -  -183 

Influence  of  gravity  on  the  circulation  -  -  -     188 

Section  VII. — The  Lymphatic  Circulation     -  -  -     igo 

CHAPTER    IV. 

RESPIRATION. 

Section  I. — Preliminary  Anatomical  Data    -  -  -     221 

Physiological  anatomy  of  the  respiratory  apparatus  -     222 

Blood-supply  of  the  lungs       -  -  -  -  _     222 

Section  II. — Mechanical  Phenomena  of  External  Respira- 
tion .-.--..     224 
Types  of  respiration    -  -  -  -  -  -228 

Artificial  respiration    --....     229 

Respiratory  sounds     --....     230 

Frequency  of  respiration         -  -  -  .  -233 

Vital  capacity  -  -  -  -  -  -235 

Intrathoracic  pressure  -----     235 

Respiratory  pressure  -  -  -  -  .  -237 

Section  III. — The  Chemistry  of  External  Respiration      -  238 

Inspired  and  expired  air  -  -  -  -  -  238 

Respiratory  quotient  ------  240 

Ventilation       ----.-. 

The  quantity  of  carbon   dioxide  given   off  and   of  oxygen 

absorbed      -------  242 

Section  IV. — The  Gases  of  the  Blood  .  -  .  244 

Physical  introduction  ------  244 

Quantity  of  the  blood-gases    -----  249 

Distribution  and  condition  of  oxygen  in  the  blood    -  -  250 

Distribution  and  condition  of  carbon  dioxide  in  the  blood  -  253 

The  tension  of  the  blood-gases  -  -  -  -  25O 


241 


Kii  CONTENTS 

PACE 

Section  V. — Internal  or  Tissue  Respiration             -             -  263 

Seats  of  oxidation        ..-.--  263 

Respiration  of  muscle               -             -             -             -             -  265 

Nature  of  the  oxidative  process          -             -             -             -  267 

Section    VI. — Relation    of    Respiration    to    the    Nervous 

System         --.-.-.  268* 

The  respiratory  centre  and  its  connections    -              -              -  268 

Regulation  of  respiration  through  the  vagus  -             -             -  270 

Action  of  other  afferent  fibres  on  the  respiration       -             -  274 

The  chemical  regulation  of  the  respiration     -             -             -  275 

Apnoea               .-..__-  277 

Automaticity  of  the  respiratory  centre            .             -              -  278 

Special  modifications  of  the  respiratory  movements  -             -  281 

Section  VII. — The  Influence  of  Respiration  on  the  Blood- 
Pressure    -------  283 

Section  VIII. — The  Effects  of  breathing   Condensed  and 

Rarefied  Air         .--_.-  289 

Section  IX. — Cutaneous  Respiration               -            -            -  292 

CHAPTER  V. 
VOICE  AND  SPEECH. 

Voice           -----_.-  301 

Speech        --.-..             -            .  306 

CHAPTER  VI. 
DIGESTION. 

Section  I. — Preliminary  Anatomical  and  Chemical  Data  -  312 

Anatomy  of  alimentary  canal             -             -             -             -  313 

Section  II. — Mechanical  Phenomena  of  Digestion  -            -  315 
Mastication      -             -             -             -             -             -             -315 

Deglutition       -  -  -  -  -  _  -316 

Movements  of  stomach  -  -  -  _  . 

Movements  of  intestines  -  -  -  _  . 

Influence    of   central    nervous    system    on   gastro-intestinal 

movements  -----.. 

Defaecation       ----__.  325 

Vomiting          --___..  328 

Section  III. — Chemistry  of  the  Digestive  Juices— Ferments  330 

Saliva                -..-...  ^^3 

Gastric  juice    ----...  3^3 

Antiseptic  functions  of  gastric  juice  -             -             -             .  3^0 


320 
322 

325 


PAGK 


CONTENTS 

Section  III.  {continued) — 

Pancreatic  juice            -----_  3^2 

Bile      - 357 

Succus  entericus           ----_.  35^ 

Section  IV. — Secretion  of  the  Digestive  Juices — Micro- 
scopical Changes  in  the  Gland  Cells  -  -  .  353 
Changes  in  pancreas  and  parotid  during  secretion  -  -  369 
Changes  in  gastric  glands  during  secretion  -  -  .  371 
Changes  in  mucous  glands  during  secretion  -  -  .  ^75 
Mode  of  formation  of  the  digestive  juices  ...  377 
Why  the  tissues  of  digestion  are  not  affected  by  the  digestive 
ferments        --.-...  382 

Section    V. — Influence    of    the    Nervous    System    on    the 

Digestive  Glands  ------  38c 

Influence  of  nervous  system  on  salivary  glands         -             -  385 

Influence  of  nervous  system  on  gastric  glands             -             -  39:; 

Influence  of  nervous  system  on  the  pancreas  -             -             -  39^ 

Secretin             -------  ^^qi 

Influence  of  nervous  system  on  secretion  of  bile         -             -  405 
Influence  of  nervous  system  on  the  secretion  of  intestinal 

juice               -             -             -             -             -             .             -  408 

Secretion  of  the  digestive  juices  (summary)    -             -             .  409 

Section  VI.— Survey  of  Digestion  as  a  Whole        -             -  410 

Reaction  of  intestinal  contents            -             -             -             .  414 
Bacterial  digestion       -             -             -             -             -             -416 

Faeces  ------..  418 

CHAPTER    VII. 

ABSORPTION. 

Section  I. — Preliminary  Physico-Chemical  Data      -             -  420 

Imbibition,  diffusion,  and  osmosis       -              -              -              _  420 

Electrolytes     -------  ^22 

Surface  tension  -  -  -  _  .  -^^^ 

Adsorption       ---.-..  ,,, 

Section  II. — Mechanism  of  Absorption            -             -             -  42 "5 

Theories  of  absorption              -             -             -             .             -  427 

Permeability  of  intestinal  epithelium-              -              -              -  4U 

Absorption  from  the  peritoneal  cavity            -             -             -  433 

Section  III. — Absorption  of  the  Various  Food  Substances   -  435 

Absorption  of  fat         -             -             -             -             -             -  41s 

Absorption  of  carbo-hydrates               -             -             -             -  430 

Absorption  of  water  and  salts             ...             -  ..q 

Absorption  of  proteins  -           -             -             -                           -  44i 


XVI  CONTENTS 

CHAPTER  XIII. 
THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES. 

PAGE 

Section  I. — Preliminary  Observations — Physical  and  Tech- 
nical Data              ......  6g6 

Cilia     -             -             -             -             -             -             -             -  707 

SixTioN     II. — Physical     Properties     and     Stimulation    of 

Muscle        -------  709 

Elasticity  of  muscle     ------  709 

Stimulation  of  muscle               -              -              -              -              -  711 

Direct  excitability  of  muscle  -----  712 

Section  III. — Physical  and  Mechanical  Phenomena  of  the 

Muscular  Contraction     -----  716 

Optical  phenomena — structure  of  muscle        -              -             -  yi6 

Mechanical  phenomena            -             -             -             -             -  719 

Muscular  fatigue           ------  723 

Electrical  tetanus        ------  730 

Voluntary  contraction              -----  734 

Thermal  phenomena  and  transformation  of  energy  in  mus- 
cular contraction      ------  736 

Relation  between  mechanical  energy  and  heat-production  in 

active  muscle            ------  739 

Section  IV. — Chemical  Phenomena  of  Muscular  Contraction  741 

Formation  of  lactic  acid         -----  743 

The  substances  metabolized  in  muscular  contraction              -  745 

CHAPTER  XIV. 

NERVE. 

Section   I. — The   Nerve-Impulse    or   Propagated    Disturb- 
ance: its  Initiation  and  Conduction   -            -            -  755 
Stimulation  of  nerve  ------  757 

Excitability  of  nerve  ------  758 

Electrotonus    -------  759 

Conduction  in  nerve    ------  764 

Velocity  of  the  nerve-impulse              -              -              -              -  767 

Section  II. — Chemistry,  Degeneration,  and  Regeneration 

OF  Nerve    -------  768 

Chemistry  of  nerve      ------  768 

Degeneration  of  nerve              -----  765 

Regeneration  of  nerve              -----  772 

Trophic  nerves             _---.-  778 

Classification  of  nerves            -----  780 


CONTENTS  xvii 

CHAPTER  XV. 
ELECTRO-PHYSIOLOGY. 

PAGE 

Currcnts  of  rest  and  action             _             .             -             _             -  796 

Relation  between  action  current  and  functional  activity  -             -  797 

Polarization  of  muscle  and  nerve  -----  802 

Elcctrotonic  currents          ------  803 

Heart-currents        -------  806 

Human  electro-cardiogram              _             -             -             -             -  808 

Glandular  currents               ------  810 

Eye-currents  -  -  -  -  -  -  -811 

Electric  fishes         -  -  -  -  -  -  -812 

CHAPTER  XVL 

THE  CENTRAL  NERVOUS  SYSTEM. 

Section  I. — Structure — ^Histological  Elements        -            -  819 
Development  -              -              -             -             -              -             -821 

Histological  elements                -             -             -             -             -  822 

Nutrition  of  the  neuron           -----  830 

Section  II.— General  Arrangement  of  the  Grey  and  White 

Matter  in  the  Central  Nervous  System         -             -  833 

Section  III. — Arrangement  of  Grey  and  White  Matter  in 

Spinal  Cord           -            -            -            -            -            -  835 

Tracts  of  the  cord        ------  838 

Section  IV. — Arrangement  of  Grey  and  White  Matter  in 

THE  Upper  Portion  of  the  Cerebro-Spinal  Axis         -  84 1 

Section  V. — Connections  of  the  Long  Paths  of  the  Cord  842 

Section  VI. — Paths  from  and  to  the  Cortex            -             -  850 

Section    VII. — Connections    of    Brain    Stem    with    Cord — 

Connections  of  Cerebellum       ....  856 

Section  VIII. — Functions  of  the  Central  Nervous  System 

— the  Spinal  Cord             -             -             .             -             .  859 

Decussation  of  the  sensory  paths        -             -             -             .  866 

Reflex  action  -------  869 

Principle  of  the  common  path             -             -             -             -  871 

Role  of  the  receptor  in  reflex  action    -             -             -             -  872 

Characteristic  properties  of  the  reflex  arc       -             -             -  ^^74 

Irradiation  of  reflex  action      -----  877 

Co-ordination  of  reflexes          -             .             ,             -             -  880 

Influence  of  the  brain  on  spinal  reflexes          .             -             -  882 

Automatism  of  the  spinal  cord            ....  888 


xviii  CONTENTS 

PAGE 

Section  IX. — The  Cranial  Nerves       -             -             -             -  8qi 

Section  X. — Functions  of  the  Brain               ...  go2 

Functions  of  the  cerebellum  -----  904 

Equilibration  and  orientation               _              .             _              -  907 
Forced  movements       -              -              -              -             -              -912 

Functions  of  the  cerebral  cortex         _              -             -              -  914 

Motor  areas     -------  918 

Histological  differentiation  of  the  cortex         -             .              -  924 
Sensory  areas  -             -             -             -             -             -             -931 

Aphasia             -_.-__-  934 

Localization  of  function  in  central  nervous  system    -              -  940 

Reaction  time                -              -              -              -             -              -  947 

Section  XI. — Fatigue  and  Sleep — Hypnosis  -             -             -  947 
Section  XII.- — Size  of  Brain  and   Intelligence — Cerebral 
Circulation — Chemistry  of  Nervous  Activity — Cere- 

bro-spinal  Fluid    -             _           -            _            -            .  952 

CHAPTER  XVII. 

THE  AUTONOMIC  NERVOUS  SYSTEM.               -  963 

CHAPTER  XVIII. 

THE  SENSES. 

The  Senses  in  General              -----  966 

Section  I. — Vision           .-._--  968 

Physical  introduction               _             _             .             -             -  968 

Structure  of  the  eye    ------  974 

Chemistry  of  the  refractive  media      -             -             -             -  976 

Refraction  in  the  eye  ------  977 

Accommodation            ------  980 

Functions  of  the  iris    ------  986 

Defects  of  the  eye        ------  987 

Ophthalmoscope          ------  991 

Skiascopy         -------  994 

Diplopia           -------  997 

Steroscopic  vision         ------  999 

Visual  judgments  and  illusions            .             -             .              -  1000 

Purkinje's  figures         ------  1002 

Blind  spot        -------  1004 

•Rods  and  cones  in  vision        -----  1005 

Talbot's  law    -------  loio 

Colour  vision  -------  loii 

Contrast            ..-----  1016 

Perimetry         -------  ioi8 


CONTENTS 


Section  I.  {continued) — 

Colour-blindness  -  -  -  _ 

Movements  of  the  eyes  .  _  _ 

Section  II. — Hearing      -  -  -  - 

Section  III.— Smell  and  Taste 

Section  IV. — Cutaneous  and  Internal  Sensatfo.vs 
Tactile  senses  .  _  _  . 

Sensations  of  temperature        -  _  _ 

Pain  -----. 
Phenomena  after  section  of  cutaneous  nerves 
Muscular  sense  _  .  _  _ 

Sensations  of  hunger  and  thirst 


PAGE 
IOI9 
1022 
1024 

1035 
1038 
1038 
IO4I 

i'J43 
1045 
1052 

1054 


CHAPTER  XIX. 
REPRODUCTION. 

Regeneration  of  tissues      -             -  - 
Reproduction  in  the  higher  animals 

Menstruation           .             .             .  . 

Development  of  the  ovum  -             -  - 

Parthenogenesis      -              -              -  . 

Formation  of  the  embryo  -              -  - 
Development  of  the  count ctioi is     - 
Exchange  of  materials  in  the  placenta 
Metabolism  of  the  embryo 
Parturition 

Milk             .             -             -             .  - 
Cultivation  of  tissues  outside  of  the  body- 

Transplantation  of  tissues  -             -  - 

Parabiosis  -             -             -            -  - 

APPENDIX            .            -            -  . 

INDEX       -            ...  - 


1074 

1075 
1076 
1078 
loSo 
1081 
1083 
1085 
1089 
1093 

1095 
1097 
1098 


1103 
1104 


PRACTICAL   EXERCISES. 

CHAPTER  I. 

General  reactions  of  proteins  -  -  . 

Colour  reactions  of  proteins  -  .  _ 

Precipitation  reactions  of  proteins 
Special  reactions  of  groups  of  proteins 
Reactions  of  derivatives  of  proteins 
Carbo-hydrates        ----- 
Fats  ---... 

Scheme  for  testing  for  proteins  and  carbo-hydrates 


7 

8 

8 

9 

9 

10 

II 

13 


CONTENTS 


CHAPTER  II. 


1.  Reaction  of  blcod         -             -             -             -             •             -  62 

2.  Specific  gravity  of  blood          -             -             -             •             -  62 

3.  Coagulation  of  blood    -             -             -             -             -             -  62 

4.  Preparation  of  fibrin-ferment  -              -              -              -              *  65 

5.  Preparation  of  extracts  containing  thrombokinase    -             -  65 

6.  Serum  --------65 

7.  Action  of  serum  on  artery  rings           -             -             -             -  66 

8.  Comparison  of  action  of  serum  and  epineplirin  on  artery  rings  66 

9.  Comparison  of  action  of  serum  and  plasma  on  artery  rings     -  66 

10.  Enumeration  of  the  blood -corpuscles  -             -             -             -  67 

11.  Haematocrite     -  -  -  -  -  -  -68 

12.  Electrical  conductivity  of  blood           -             -             -             -  68 

13.  Opacity  of  blood           -             -             -             -             -             -  70 

14.  Laking  of  blood  -  -  -  -  -  -70 

15.  Haemolysis  and  agglutination  -  -  -  -  -7^ 

16.  Osmotic  resistance  of  coloured  corpuscles        -             -             -  73 

17.  Blood-pigment               -             -             -             -             -             -  73 

(i)  Preparation  of  haemoglobin  crystals  -             -             -  73 
(2)  Spectroscopic  examination   of  haemoglobin   and   its 

derivatives               -             -             -             -             -  74 

{3)  Guaiacum  test  for  blood         -             -             -             -  7^ 

(4)  Quantitative  estimation  of  haemoglobin         -             -  76 

(5)  Haemin  test  for  blood-pigment            -             -             -  78 

CHAPTER  III. 

1.  Microscopic  examination  of  the  circulating  blood       -             -  191 

2.  Anatomy  of  the  frog's  heart    -----  191 

3.  Beat  of  the  heart          -             -             -             -             -             -  192 

4.  Apex  of  the  heart          ------  192 

5.  Heart  tracings               ..--.-  192 

6.  Dissection  of  vagus  and  cardiac  sympathetic  in  frog  -              -  194 

7.  Stimulation  of  the  vagus  in  the  frog  -              -              -              -  196 

8.  Stimulation  of  the  junction  of  the  sinus  and  auricles  -              -  196 

9.  Action  of  muscarine  and  atropia  on  the  heart              -             -  197 

10.  Stannius'  experiment  ------  197 

11.  Stimulation  of  cardiac  sympathetic  in  frog     -              _              -  197 

12.  Action  of  inorganic  salts  on  heart-muscle        -             -             -  198 

13.  Action  of  the  mammalian  heart            -             -             -             -  199 

14.  Perfusion  of  the  isolated  mammalian  heart     -             -             -  203 

15.  Action  of  the  valves  of  the  heart          .             -             .             .  204 

16.  Sounds  of  the  heart      ------  205 

17.  Cardiogram       -------  205 


CONTENTS  XXI 

PACB 

i8.  Sphygmographic  tracings         ...             -             -  206 

19.  Venous  pulse  tracing  from  jugular      ....  207 

20.  Polygraph  tracings       -  -  -  -  -  -207 

21.  Plethysmographic  tracings      -----  208 

22.  Pulse-rate         -.---.             _  208 

23.  Blood-pressure  tracing              -             -             .             .             .  208 

24.  Estimation  of  arterial  pressure  in  man             -             -             -  211 

25.  Influence  cf  position  of  the  body  on  blood-pressure    -             -  211 

26.  Effects  of  haemorrhage  and  transfusion  on  blood-pressure       -  212 

27.  Influence  of  proteoses  on  blood-pressure          .             _             -  213 

28.  Effect  of  suprarenal  extract  on  blood-pressure            -             -  214 

29.  Action  of  epinephrin  on  artery  rings   -             -             -             -  214 

30.  Section  and  stimulation  of  cervical  sympathetic  in  rabbit     -  215 

31.  Determination  of  the  circulation-time              _             -             -  215 

32.  Measurement  of  the  blood-flow  in  the  hands  -             -             -  218 

33.  Vaso-motor  reflexes     ------  220 

CHAPTER  IV. 

1.  Tracing  of  the  respiratory  movements  in  man               -             -  293 

2.  Production  of  apnoea  and  periodic  breathing  in  man               -  294 

3.  Tracing  of  the  respiratory  movements  in  animals      -             -  294 

4.  Heat  dyspnoea  -------  296 

5.  Measurement  of  volume  of  air  inspired  and  expired  -             -  297 

6.  Cardio-pneumatic  movements               -             -             .             _  297 

7.  Auscultation  of  the  lungs          -----  298 

8.  Measurement  of  the  respiratory  pressure         -             -             .  298 

9.  Estimation  of  carbon  dioxide  and  water  given  off  by  an  animal  299 

10.  Muscular  contraction  in  the  absence  of  free  oxygen    -             -  300 

11.  Oxidizing  ferments       -----.  300 

CHAPTERS  VI.  AND  VII. 

1.  Contraction  of  isolated  intestines  in  Ringer's  solution             -  446 

2.  Effect  of  serum  on  the  contractions  of  intestinal  segments     -  447 

3.  Action  of  epinephrin  on  intestinal  segments   -             -             -  447 

4.  Quantitative  estimation  of  ferment  action       -             -             .  4^7 

5.  Chemistry  and  digestive  action  of  saliva          -             -             -  4^8 

6.  Stimulation  of  the  chorda  tympani     -             -            -            -  450 

7.  Effect  of  drugs  on  the  secretion  of  saliva         -             -             -  451 

8.  Digestive  action  of  gastric  juice  -  -  -  -452 

9.  To  obtain  chyme  and  gastric  juice       .              -              .              -  433 

10.  Digestive  action  of  pancreatic  juice    -             -             .             -  454 

11.  Chemistry  of  bile           .--_.-  436 

12.  Microscopical  examination  of  f.Tces     -             -             -             -.  457 


xxii  CONTENTS 

PAGE 

13.  Absorption  of  fat  -  -  -  -  -     457 

14.  Time   required   for   digestion   and   absorption    of    food   sub- 

stances        ---.-.-     438 

15.  Quantity  of  cane-sugar   inverted   and  absorbed  in  a  given 

time  --.___-     438 

16.  Auto-digestion  of  the  stomach  -  _  -  -     459 


CHAPTER  IX. 

1.  Specific  gravity  of  urine  «  _  _  .  -     308 

2.  Reaction  of  urine  --_-_-     308 

3.  Chlorides  in  urine  --_-_-     308 

4.  Phosphates  in  urine      ------     309 

5.  Sulphates  in  urine         _--..-     310 

6.  Indoxyl  in  urine  -  -  -  -  -  -510 

7.  Urea     --.--._-     511 

8.  Ammonia  in  urine        -  -  -  •  -  -     513 

9.  Total  nitrogen  in  urine  -  -  -  -  -.514 

10.  Uric  acid  -  -  -  -  -  -  -515 

11.  Kreatinin  ->__-_-     313 

12.  Hippuric  acid  -  -  -  -  -  _      .       -     316 

13.  Proteins  in  urine  ---___     316 

14.  Sugar  in  urine  -------     317 

13.  Pentoses  in  urine  ------     320 

16.  Acetone  in  urine  -  -  -  -  -  -521 

17.  Determination  of  the  freezing-point  of  urine   -  -  -     521 

18.  Examination  of  urine  ------     323 

19.  Urinary  sediments        ------     323 


CHAPTERS  X.,  XL,  AND  XII. 

1.  Glycogen            ----__-  689 

2.  Catheterism      -------  690 

3.  Experimental  glycosuria           -----  690 

(i)   Injection  of  sugar  into  the  blood        -              .              -  6go 

(2)  Phlorhizin  glycosuria               -              -              _              .  691 

(3)  Alimentary  glycosuria             -             -             -              _  59J 

4.  Milk      -----.-.  691 

5.  Cheese  --------  692 

6.  Flour    --------  692 

7.  Bread  --------  693 

8.  Excretion  of  urea  (and  total  nitrogen)  and  proteins  in  food  -  693 

9.  Action  of  epinephrin    ------  593 

10.  Measurement  of  the  heat  given  off  in  respiration        -             -  694 


CONTENTS 


CHAPTERS  XIII.  AND  XIV. 

FAOK 

1.  DilTcrcnce  of  make  and  break  induction  shocks          -             -  780 

2.  Stimulation  by  the  voltaic  current      -             -             .             -  7S3 

3.  Ciliary  motion                .-.-._  784 

4.  Direct  excitability  of  muscle — curara  -             -             -             -  784 

5.  Graphic  record  of  '  twitch  '     -             -             -             -             -  784 

6.  Influence  of  temperature  on  the  muscle-curve               -             -  786 

7.  Influence  of  load  on  the  muscle-curve               .              _              .  y86 

8.  Influence  of  fatigue  on  the  muscle-curve          .             .             .  y86 

9.  Seat  of  exhaustion  in  fatigue  of  the  muscle-nerve  preparation  786 

10.  Influence  of  veratrLne  on  muscular  contraction  -              -  787 

11.  Measurement  of  the  latent  period  of  muscular  contraction     -  788 

12.  Summation  of  stimuli  ------  789 

13.  Superposition  of  contractions  -----  789 

14.  Composition  of  tetanus  .             _             >             -             _  ySg 

15.  Contraction  of  smooth  muscles  _             .             _             _  790 

16.  Velocity  of  the  nerve-impulse  _              -              _              .  ygi 

17.  Chemistry  of  muscle     ------  792 

18.  Reaction  of  muscle  in  rest,  activity,  and  rigor  -             -  793 

CHAPTER  XV. 

1.  Galvani's  experiment    ------     814 

2.  Contraction  without  metals     -  -  -  -  -814 

3.  Secondary  contraction  .  -  -  _  _     814 

4.  Demarcation  and  action  currents  with  capillary  electrometer     814 

5.  Action  current  of  the  heart      -  -  -  -  -816 

6.  Electrotonus     -------     816 

7.  Paradoxical  contraction  .  -  .  -  -     816 

8.  Alterations  in  excitability  and  conductivitj^  produced  in  nerve 

by  a  voltaic  current  -  -  -  -  -816 

9.  Formula  of  contraction  -  -  -  -  -817 

10.  Formula  of  contraction  for  (human)  nerves  in  situ     -  -     818 

11.  Ritter's  tetanus  -  -  -  -  -  -81S 


CHAPTER  XVI. 

1.  Section  and  stimulation  of  nerve-roots  -  -  -  957 

2.  Reflex  action  in  the  '  spinal  '  frog        -  -  -  -  938 

3.  Reflex  time       -------  958 

4.  Inhibition  of  the  reflexes  -  .  -  -  -  939 

5.  Spinal  cord  and  muscular  tonus  -  _  -  -  939 

6.  Spinal  cord  and  tonus  of  the  bloodvessels        -  -  -  939 

7.  Action  of  strychnine    ------  939 


CONTENTS 


8.  Mammalian  spinal  preparation  ...  -  959 

9.  Reflexes  in  man  ......  951 

10.  Excision  of  cerebral  hemispheres  in  the  frog  -  -  -  961 

11.  Excision  of  cerebral  hemispheres  in  the  pigtMjn  -  -  961 

12.  Stimulation  of  the  motor  areas  in  the  dog       -  -  _  962 


CHAPTER  XVIII. 

1.  Dissection  of  the  eye    ------  1058 

2.  Formation  of  inverted  image  on  the  retina     .             -             -  1059 

3.  Helmholtz's  Phakoscope           -             .             «            »             _  1059 

4.  Scheiner's  experiment  -             -             -              .             -             .  1060 

5.  Kiihne's  artificial  eye  ------  1061 

6.  Astigmatism  (ophthalmometer)             -              _             «             .  1062 

7.  Spherical  aberration     ---.».  1063 

8.  Chromatic  aberration  ---.-.  1063 

9.  Measurement  of  the  field  of  vision        .             -             -             -  1063 

10.  Mapping  the  blind  spot            -             .             -             _             .  1064 

11.  The  yellow  spot            -             -             -             -                           _  1064 

12.  Ophthalmoscope           •             -             ...             -  1065 

13.  Retinoscopy      -----..  1066 

14.  PupUlo-dUator  and  constrictor  fibres  -             -                           -  1067 

15.  Colour-mix  ng  -------  1068 

16.  After-images     -------  1068 

17.  Retinal  fatigue              ----..  1068 

18.  Visual  acuity    -------  1068 

19.  Colour-blindness           -----_  1069 

20.  Talbot's  law     -------  1070 

21.  Purkinje's  figures          ------  1070 

22.  Relation  of  pitch  and  vibration  frequency      -             -             -  1070 

23.  Beats    --------  1070 

24.  Sympathetic  vibration              -             .             -             .             -  1070 

25.  Galton's  whistle             --.-._  1070 

26.  Cranial  conduction  of  sound    -             ...             -  1070 

27.  Taste    -             -             -             .             -             -             .             -  1070 

28.  Smell    --------  1071 

29.  Touch  and  pressure      ------  1071 

30.  Temperature  sensations            .             _             .             .             .  5072 

31.  Pain      --------  1073 

CHAPTER  XIX. 

Contractions  of  isolated  uterine  rings  -            .            -            -  noi 


A    MANUAL   OF    PHYSIOLOGY 


CHAPTER  I 
INTRODUCTION 

Living  matter,  whether  it  is  studied  in  plants  or  in  animals,  has 
certain  peculiarities  of  chemical  composition  and  structure,  but 
especially  certain  peculiarities  of  action  or  function,  which  mark  it 
off  from  the  unorganized  material  of  the  dead  world  around  it. 

Chemical  Composition  of  Living  Matter.^ — Although  we  cannot 
analyze  the  living  substance  as  such,  we  can  to  a  certain,  but 
limited,  extent  reconstruct  it,  so  to  speak,  from  its  ruins.  When 
subjected  to  analytical  processes,  which  necessarily  kill  it,  living 
matter  invariably  yields  bodies  of  the  class  of  proteins,  exceedingly 
complex  substances,  which  have  approximately  the  following  com- 
position: Carbon,  51-5  to  54-5  per  cent.;  oxygen,  20*9  to  23-5  per 
cent. ;  nitrogen,  15-2  to  17  per  cent. ;  hydrogen,  6-9  to  7-3  per  cent., 
with  small  quantities  of  sulphur.  Nncleo-proteins,  which  are  com- 
pounds of  ordinary  proteins  with  nucleic  acids,  a  series  of  sulphur- 
free  organic  acids  rich  in  phosphorus,  are  constantly  met  with. 
Certain  carbo-hydrates,  composed  of  carbon,  hydrogen,  and  oxygen 
(the  last  two  in  the  proportions  necessary  to  form  water),  of  which 
glycogen  (CgHioOg)^  may  be  taken  as  a  type,  appear  to  be  always 
present.  Fats,  which  consist  of  carbon,  hydrogen,  and  oxygen,  and 
of  which  tristeaiin,  a  compound  of  stearic  acid  with  glycerin,  of 
the  formula  C3H5,3(Ci8H3502),  may  be  given  as  an  example,  are 
often,  and  certain  lipoids,  e.g.,  lecithin  (p.  4),  are  always,  found. 
Finally,  water  and  certain  inorganic  salts,  such  as  the  chlorides  and 
phosphates  of  sodium,  potassium,  and  calcium,  are  constantly  present. 

The  Proteins. — The  constitution  of  the  protein  molecule  is  still  un- 
known ;  but  when  proteins  are  broken  down  by  the  action  of  ferments, 
such  as  exist  in  gastric  and  in  pancreatic  juice,  or  by  chemical  methods 
— for  example,  b^  boiling  with  dilute  acids — the  most  important  of 
the  cleavage  products  are  various  amino-acids  (p.  354).  It  has  there- 
fore been  suggested  that  proteins  arc  built  up  by  tlic  linking  together  ot 
amino-acids,  the  different  proteins  differing  quantitatively  or  quali- 
tatively as  regards  the  amino-acids  present  (E.  Fischer).  Thus  serum- 
albumin  and  egg-albumin  yield  no  glycin  or  glycocoll  (amino-acctic 
acid,  CH2.NH2.COOH),  while  glycin  is  constantly  found  among  the 
cleavage    products    of    serum-globulin.     And    while    leucin    (o-amino- 


INTRODUCTION 


isobutylacetic  acid)  is  present  to  the  extent  of  about  20-5  per  cent,  in 
the  cleavage  products  of  (horse's)  serura-albumm,  (hen  s)  egg-albumin 
yields  only  7"  i  per  cent,  .      .     ,      •     / 

On  the  other  hand,  egg-albumin  yields  S'l  per  cent,  of  alanm  (ammo- 
propionic   acid.   C2H4.NH2.COOH),   while   serum-albumm   yields  only 
2-  7  per  cent      Of  the  aromatic  amino-acids— that  is,  amino-acids  united 
to  the  benzene  ring— phenyl-alanin  (amino-propionic  acid  in  which  one 
atom  of  H  is  replaced  by  phenyl,  CgHe)  is  obtained  to  the  extent  of 
4-4  per  cent,  from  egg-albumin,  and  a  little  over  3  per  cent,  from  serum- 
albumin.     Tyrosin  or  oxyphenyl-alanin  (amino-propionic  acid  m  which 
a  H  atom  is  replaced  by  oxyphenyl,  CgH^.OH)  appears  to  the  amount 
of  rs  per  cent,  among  the  cleavage  products  of  cgg-albumm.  and  to 
the  amount  of  21  per  cent,  among  those  of  serum-albumm       It  is  an 
interesting  point  in  this  connection  that  gelatin,  which  yields  16-5  per 
cent    of  glycin     yields  no  tyrosin  at  all;   tryptophane,   an  aromatic 
amino-acid  still  more  complex  than  tyrosin,  is  also  absent.     These  facts 
afford  an  explanation  of  certain  colour  reactions  of  proteins  long  known 
empirically,  but  only  recently  understood  (p.  8) .     The  process  by  which 
the  protein  molecule  is  thus  decomposed  is  called  hydrolysis — that  is, 
the  molecule  takes  up  water,  and  then  splits  into  smaller  molecules. 
The  hydrolysis  occurs  in  various  stages,  bodies  like  acid-  or  alkali- 
albumin  (meta-  or  infra-proteins)  being  first  formed,  then  proteoses, 
then  peptones.     The  peptones  are  further  split  into  bodies  containing 
a  relatively  small  number  of  amino-acids  linked  together.     These  bodies 
are  called  polypeptides,  which  finally  are  decomposed  so  as  to  yield  the 
individual  amino-acids,  also  called  in  this  connection  the  peptides  or 
monopeptides,  the  "  building-stones  "  out  of  which  the  protein  molecule 
is  constructed.     The  inverse  process  can  also  be  carried  on  to  a  certain 
extent,  and  Fischer  has  taken  an  important  step  towards  the  eventual 
synthesis  of  proteins  by  showing  how  polypeptides  of  increasing  com- 
plexity can  be  built  up  by  linking  amino-acids  together.     When  two 
amino-acids  are  so  united,  the  resulting  compound  is  called  a  dipeptide ; 
with  three  amino-acids  we  get  tripeptides,  etc.     Still  more  complicated 
polypeptides  may  thus  be  formed  in  the  laboratory,  which  give  some  of 
the  characteristic  reactions  of  peptones. 

The  numerous  substances  included  in  the  group  of  proteins  may  be 
classified  as  follows,  beginning  with  the  simplest: 

1.  Protamins.  such  as  the  bodies  called  salmin  and  stunn  present  in 

fish-sperm.  ,      ,  ,  ^,  ,  •       .1. 

2.  Histones,  bodies  separated  from  blood-corpuscles.  Globm.  the 
protein  constituent  of  haemoglobin,  is  one  of  them.  Unlike  the  other 
groups  of  proteins,  they  are  precipitated  by  ammonia. 

3.  Albumins. 

4.  Globulins. 

5.  Sclero-proteins  or  albuminoids,  such  as  gelatm  and  keratm. 

6.  Phospho-proteins,  including  such  substances  as  vitellin,  a  body 
obtainable  from  egg-yolk,  and  cascinogen,  the  chief  protein  of  milk. 
They  are  rich  in  phosphorus,  but  are  to  be  distinguished  from  nucleo- 
proteins,  which  also  contain  a  relatively  large  amount  of  phosphorus, 
by  the  fact  that  they  do  not  yield  the  purin  bases,  the  characteristic 
products  of  the  decomposition  of  nucleo-proteins. 

7  Conj  ugated  proteins,  substances  in  which  the  protein  molecule  is 
united  to  another  constituent,  usually  spoken  of  as  a  '  prosthetic  '  group. 
Thus  the  nucleo-proteins  consist  of  protein  united  with  nucleic  acid, 
the  chromo-proteins  [e.g..  haimoglobin.)  of  protein  united  with  a  pig- 
ment, and  the  gluco-proteins  {e.g..  mucin)  of  protein  united  with  a 
carbo-hydrate  group. 


CHEMICAL  COMPOSITION  OF  LIVING  MATTER  3 

A.mong  the  derivatives  of  proteins,  the  most  important  are  those 
already  mentioned  as  being  produced  in  protein-hydrolysis,  viz.: 

(a)  Mcta-protcins. 

{b)  Proteoses,  including  albumose,  the  proteose  derived  from  albu- 
min; globulose,  that  derived  from  globulin;  gelatose,  that  derived  from 
gelatin,  etc.  The  proteoses  may  be  further  subdivided,  according  to 
the  order  in  which  they  are  formed  in  digestion  into  pro  to -proteoses, 
hetero-proteoses,  and  deutero-proteoses. 

[c)  Peptones. 

[d)  Polypeptides.  The  majority  of  these  are  artificial  products, 
formed  by  the  synthesis  of  amino-acids,  although  some  can  be  obtained 
from  proteins  by  hydrolysis.  Only  a  few  of  those  hitherto  prepared 
give  the  biuret  test. 

However  formidable  the  above  list  may  appear  to  the  student,  it 
gives  an  inadequate  idea  of  the  extreme  complexity  of  the  protein  class 
and  its  ricliness  in  individuals.  For,  apart  from  the  fact  that  the  list 
has  been  purposely  left  incomplete,  especially  as  regards  the  numerous 
vegetable  proteins,  there  is  the  best  evidence  that  proteins  of  the  same 
name  from  different  animal  species  have  certain  properties  which  dis- 
tinguish them  from  each  other.  The  serum-albumins  can  be  crystal- 
lized much  more  easily  in  some  animals  than  in  others.  The  same  is 
conspicuously  true  of  the  haemoglobins,  which  differ  also  in  certain 
animals  in  the  relative  proportion  of  sulphur  and  iron  in  the  molecule, 
as  well  as  in  the  crystalline  form.  Even  when  no  chemical  or  physical 
dififerences  have  as  yet  been  made  out,  proteins  of  the  same  name  from 
the  blood  or  organs  of  different  species  show  notable  '  specific  '  differ- 
ences when  subjected  to  certain  biological  tests  (see,  e.g.,  the  paragraph 
on  Precipitins,  p.  31 ;  and  that  on  Anaphylaxis,  p.  32). 

Carbo-Hydrates. — The  most  important  carbo-hydrates  in  their  physio- 
logical relations  are   dextrose,    levulose,   galactose,   lactose,    maltose, 
sucrose  (cane-sugar),  starch,  and  glycogen.     As  regards  their  chemical 
constitution,  the  simplest  carbo-hydrates  are  aldehydes  or  ketones — 
that  is,  the  first  oxidation  products  of  primary  and  secondary  alcohols 
respectively.     Thus  dextrose  is  the  aldehyde  of  sorbite,  a  hexatomic 
alcohol  (an  alcohol  containing  six  OH  groups),  while  levulose  is  the 
ketone  of  the  isomeric  alcohol  called  mannite,  and  galactose  the  alde- 
hyde of  the  isomeric  alcohol  called  dulcite.     The  sugars  containing  six 
carbon  atoms  are  termed  hcxoses.     They  include  dextrose,  levulose, 
and  galactose.     The  empirical  formula  of  these  three  simple  sugars  (or 
monosaccharides)  is  the  same   {C^H-^O^),  but,  owing  to  the  different 
arrangement  of  the  atoms  or  groups  of  atoms,  they  have  each  their 
characteristic  properties  by  which  they  can  be  easily  distinguished. 
For  example,  dextrose  rotates  the  plane  of  polarization  to  the  right, 
levulose  to  the  left.     By  the  union  or  '  condensation  '  of  two  molecules 
of  a  monosaccharide,  with  loss  of  a  molecule  of  water,  a  disaccharide  is 
formed.     Cane-sugar,  maltose,  and  lactose,  all  with  the  same  empirical 
formula,  (Cj2H220u),  are  disaccharides.     Cane-sugar  yields  on  hydro- 
lysis a  mixture  of  equal  parts  of  dextrose  and  levulose;  lactose,  a  mix- 
ture of  dextrose  and  galactose  ;  while  maltose  is  converted  into  dextrose. 
By  the  condensation  of  more  than  two  molecules  of  monosaccharide 
polysaccharides  are  formed,  such  as  starch,  dextrin,  and  glycogen.     The 
exact   molecular   weights   of   these   substances   are    unknown.     Their 
general  formula  can  be  written   (CgHioOg^i,,   where   n  represents  the 
number  of  monosaccharide   molecules  condensed   to   fonn   the   poly- 
saccharide, in  the  case  of  starch  probably  some  hundreds. 

Fats  and  Lipoids. — The  fats  are  compounds  of  higher  fatty  acids 
with  glycerin   (glycerin  esters).     The  ordinary  body-fat  consi.  ts  of  a 


4  INTRODUCTION 

mixture  of  three  neutral  fats  (palmitin,  stearin,  and  olein)  which  differ 
both  chemically  and  physically  from  each  other — e.g..  in  melting-point 
and  in  the  so-called  iodine  value,  the  number  which  represents  the 
amount  of  iodine  taken  up  from  a  standard  solution.  Olein  melts  at 
-5°  C,  palmitin  at  45°  C,  and  stearin  at  a  still  higher  temperature. 
It  is,  therefore,  the  presence  of  olein  which  keeps  the  body-fat  liquid 
at  the  temperature  of  the  body.  The  fats  are  soluble  in  ether,  in  hot 
alcohol,  and  in  many  other  liquids,  but  insoluble  in  water.  Besides 
the  ordinary  fats,  the  tissues  and  liquids  of  the  body  contain  phospha- 
tides, a  group  of  compounds  which  stand  in  close  relation  to  the  fats, 
but  differ  in  containing  phosphoric  acid  and  nitrogenous  bases.  The 
most  important  representative  of  this  group  is  lecithin  (C42H84NPO9), 
a  fat-like  compound  which  yields  on  decomposition,  in  addition  to 
glycerin  and  a  fatty  acid,  phosphoric  acid  and  a  nitrogen-containing 
substance  called  cholin  (p.  360).  Lecithin,  though  found  in  all  cells,  is 
especially  abundant  in  nervous  tissues.  It  is  associated  with  choles- 
terin  and  with  other  substances  which,  like  lecithin  and  cholesterin, 
are  soluble  in  ether  and  similar  solvents  of  fat.  For  this  reason  these 
substances  are  often  grouped  together  as  lipoids,  although  some  of 
them  are  chemically  different  from  fat.  Cholesterin,  for  instance,  is  an 
alcohol.  Although  usually  present  only  in  small  amount,  the  lipoids 
play  a  very  important  part  in  the  structure  and  in  the  economy  of  the 
cell. 

Structure  of  Living  Matter — ^The  Cell.* — Bioplasm  is  the  name 
given  to  the  living  matter  of  cells.  The  portion  of  the  bioplasm 
differentiated  as  the  nucleus  is  distinguished  by  the  term  karyo- 
plasm,  and  the  portion  outside  the  nucleus  by  the  term  protoplasm 
or  cytoplasm.  Protoplasm,  when  examined  in  its  most  primitive 
undifferentiated  condition  in  such  cells  as  the  amoeba  or  the  white 
blood-corpuscles,  appears  on  first  view  a  homogeneous,  structureless 
mass,  except  for  certain  granules  embedded  in  it,  and  consisting 
either  of  products  formed  by  its  activity  or  of  food  materials.  But 
even  here  more  careful  study  reveals  a  certain  complexity  of  struc- 
ture. At  the  very  least,  an  external  layer,  or  ectoplasm,  can  be  dis- 
tinguished from  the  interior  mass,  or  endoplasm.  There  is  reason 
to  believe  that  even  where  no  histological  demonstration  of  an 
ectoplasmic  layer  or  a  definite  envelope  is  possible,  the  surface  of 
the  cell  is  physiologically  different  from  its  interior.  In  many  cells 
the  protoplasm  presents  the  appearance  of  a  honeycomb  or  net- 
work, with  granules  usually  situated  at  the  nodes,  and  holding  in 
its  vesicles  or  meshes  a  fluid,  perhaps  containing  pabulum,  from 
which  the  waste  of  the  living  framework  is  made  good,  or  material 
upon  which  it  works,  and  which  it  is  its  business  to  transform. 
Some  observers,  however,  maintain  that  the  network  is  an  artificial 
appearance  produced  by  the  precipitation  of  the  colloid  constituents 
of  the  protoplasm  by  the  fixing  reagent,  or  even  by  the  coagulative 
processes  associated  with  the  act  of  dying,  and  that  the  unaltered 
liying  substance  is  a  homogeneous  fluid  or  jelly.     It  is  known  that 

*  Space  permits  only  the  slightest  sketch  of  this  subject  here.  For  de- 
tailed information  the  student  is  referred  to  textbooks  of  histology. 


STRUCTURE  OF  LIVING   MATTER  5 

changes  of  reaction  occur  when  the  living  substance  dies,  and  slight 
cha-iges  of  reaction,  i.e.,  changes  in  the  relative  concentration  of 
hydrogen  ions  (H+)  and  hydroxyl  ions  (0H-),  can  bring  about 
similar  precipitates  in  colloid  solutions.  Nevertheless  in  some  cells 
a  certain  differentiation  in  the  structure  of  the  protoplasm  can  be 
seen  during  life  and  before  the  addition  of  any  reagent,  and  in  such 
cases  there  can  be  no  doubt  that  the  structural  details  pre-exist 
and  are  not  arte-facts.  In  certain  respects  protoplasm  behaves 
like  a  liquid,  and  in  others  like  a  solid,  a  peculiarity  which  is  un- 
doubtedly associated  with  the  fact  that  its  chief  constituents  exist 
in  the  colloid  state,  as  experiments  with  such  substances  as  gelatin 
and  agar  have  shown.  In  building  up  our  typical  cell  we  start  with 
a  piece  of  protoplasm.  Somew^here  in  the  midst  of  this  we  find  a 
body  which,  if  not  absolutely  different  in  kind  from  the  protoplasm 
of  the  rest  of  the  cell  or  cytoplasm,  is  yet  marked  off  from  it  by  very 
definite  morphological  and  chemical  characters. 

This  is  the  nucleus,  generally  of  round  or  oval  shape,  and  bounded 
by  an  envelope.  Within  the  envelope  lies  a  second  network  of 
fine  threads,  which  do  not  themselves  stain  with  nuclear  dyes  such 
as  hsematoxylin.  But  in  or  on  these  '  achromatic  '  filaments  lie 
small,  highly  refractive  particles,  staining  readily  and  deeply  with 
dyes,  and  therefore  described  as  consisting  of  chromatin.  This  chro- 
matin is  either  made  up  of  nucleins  (conjugated  proteins  particu- 
larly rich  in  nucleic  acid,  and  therefore  in  phosphorus),  or  yields 
nucleins  by  its  decomposition;  and  it  seems  to  owe  its  affinity  for 
certain  staining  substances  to  the  presence  of  nucleic  acid.  The 
meshes  of  the  nuclear  reticulum  contain  a  semi-fluid  material, 
which  does  not  readily  stain.  The  nucleus  is  distinguished  from 
the  cytoplasm,  even  as  regards  its  inorganic  constituents,  by  the 
absence  of  potassium.*  Besides  the  nucleus,  another  much  smaller 
structure,  the  centrosome,  is  differentiated  from  the  protoplasm 
of  many  cells.  This  is  a  minute  dot  staining  deeply  with  such  dyes 
as  haematoxylin,  and  generally  situated  near  the  nucleus.  Sur- 
rounding it  is  a  clear  area,  the  attraction  sphere,  in  and  beyond 
which  fine  fibrils  radiate  out  into  the  cytoplasm.  Both  the  attrac  ■ 
tion  sphere  and  the  nucleus  play  an  important  part  in  division  of 
the  cell  by  the  process  known  as  karyokinesis,  or  mitosis,  or  in- 
direct division,  which  is  by  far  the  most  common  mode. 

When  the  nucleus  is  about  to  divide,  the  chromatin  granules 
arrange  themselves  into  one  or  more  coiled  filaments  or  skeins, 
which  then  break  up  into  a  number  of  separate  portions  called 

*  This  has  been  shown  microchemically.  The  potassium  is  precipitated 
by  a  solution  of  hexanitrite  of  sodium  and  cobalt  as  orange-yellow  crystals  of 
the  triple  salt,  hexanitrite  of  potassium,  sodium,  and  cobalt.  Where  very 
minute  traces  of  potassium  are  present,  ammonium  sulphide  must  be  added, 
after  washing  out  the  excess  of  the  cobalt  reagent.  Black  cobalt  sulphide  is 
thus  formed  from  the  triple  salt  (Macallum,  Frontispiece). 


6  INTRODUCTION 

chromosomes.  These  undergo  a  remarkable  series  of  transforma- 
tions, leading  eventually  to  the  segregation  of  the  nuclear  chromatin 
in  two  separate  daughter  nuclei,  each  surrounded  by  a  portion  of 
the  original  cytoplasm.  Apart  from  its  role  in  the  division,  and 
therefore  in  the  multiplication,  of  the  cell,  the  nucleus  is  now  known 
to  exert  an  influence  perhaps  not  less  important  upon  those  chemical 
changes  in  the  cytoplasm  which  are  necessary  for  its  normal  nutri- 
tion and  function.*  It  is  doubtful  whether  any  portion  of  proto- 
plasm can  permanently  sur\dve  the  loss  of  its  nuclear  material.  It 
must  be  remembered,  however,  that  nuclear  material  may  some- 
times be  present  in  diffuse  form  in  cells  which  do  not  show  a  nucleus 
in  the  histological  sense. 

When  we  carry  back  the  analysis  of  an  organized  body  as  far  as 
we  can,  we  find  that  even^'  organ  of  it  is  made  up  of  cells,  which 
upon  the  whole  conform  to  the  type  we  have  been  describing, 
although  there  are  many  differences  in  details.  Some"  organisms 
there  are,  low  dovNOi  in  the  scale,  whose  whole  activity  is  confined 
within  the  narrow  limits  of  a  single  cell.  The  amoeba  sets  up  in  life 
as  a  cell  split  off  from  its  parent.  It  divides  in  its  turn,  and  each 
half  is  a  complete  amoeba.  When  we  come  a  little  higher  than  the 
amoeba,  we  find  organisms  which  consist  of  several  cells,  and 
'  specialization  of  function  '  begins  to  appear.  Thus  the  hydra,  the 
'  common  fresh- water  polyp '  of  our  ponds  and  marshes,  has  an  outer 
set  of  cells,  the  ectoderm,  and  an  inner  set,  the  endoderm.  Through 
the  superficial  portions  of  the  former  it  learns  what  is  going  on  in 
the  world;  by  the  contraction  of  their  deeply  placed  processes  it 
shapes  its  life  to  its  environment.  As  we  mount  in  the  animal 
scale,  specialization  of  structure  and  of  function  are  found  con- 
tinually advancing,  and  the  various  kinds  of  cells  are  grouped 
together  into  colonies  or  organs.  In  some  organs  and  tissues  the 
bond  of  union  is  simple  juxtaposition  and  similarity  of  function  of 
the  constituent  cells.  But  in  others  the  union  is  protoplasmic,  pro- 
cesses of  the  cytoplasm  actually  passing  from  cell  to  cell.  This  is 
seen  in  certain  epithelial  tissues,  and  conspicuously  in  the  cardiac 
muscle. 

The  Functions  of  Living  Matter. — The  peculiar  functions  of  living 
matter  as  exhibited  in  the  animal  body  will  form  the  subject  of  the 
main  portion  of  this  book ;  and  we  need  only  say  here :  (i)  That  in  all 
living  organisms  certain  chemical  changes  go  on,  the  sum  total  of 
which  constitutes  the  metabolism  of  the  body.  These  may  be 
divided  into  {a)  integrative  or  anabolic  changes,  by  which  complex 
substances  (including  the  living  matter  itself)  are  built  up  from 

*  According  to  Hertwig,  a  precursor  of  chromatin,  '  prochromatin,'  a  sub- 
stance without  characteristic  staining  reaction,  is  formed  in  the  cytoplasm, 
taken  up  by  the  nucleus,  and  there  elaborated  into  chromatin.  From  the 
nucleus  chromatin  and  its  derivatives  return  to  the  cytoplasm  to  be  used  in 
its  function. 


FUNCTIONS  OF  LIVING  MATTER  7 

simpler  materials;  and  (&)  disintegrative  or  katabatic  changes,  in 
which  complex  bodies  (including  the  living  substance)  are  broken 
down  into  comparatively  simple  products.  In  plants,  upon  the 
whole,  it  is  integration  which  predominates;  from  substances  so 
simple  as  the  carbon  dioxide  of  the  air  and  the  nitrates  of  the  soil 
the  plant  builds  up  its  carbo-h3'drates  and  its  proteins.  In  animals 
the  main  drift  of  the  metabolic  current  is  from  the  complex  to  the 
simple;  no  animal  can  construct  its  own  protoplasm  from  the 
inorganic  materials  that  lie  around  it;  it  must  have  ready-made 
protein  in  its  food.  But  in  all  plants  there  is  some  disintegration; 
in  all  animals  there  is  some  synthesis.  The  progress  of  biochemistry 
in  recent  years  has  indeed  shown  that  the  synthetic  powers  of 
animal  cells  have  been  greatly  underestimated.  (2)  The  living  sub- 
stance is  excitable — that  is,  it  responds  to  certain  external  im- 
pressions, or  stimuli,  by  actions  peculiar  to  each  kind  of  cell. 
(3)  The  living  substance  reproduces  itself.  All  the  manifold  activities 
included  under  these  three  heads  have  but  one  source,  the  trans- 
formation of  the  energy  of  the  food.  It  is  not,  however,  upon  the 
whole,  peculiarities  in  food,  but  in  molecular  structure,  that  underlie 
the  peculiarities  of  function  of  different  living  cells.  A  locomotive 
is  fed  with  coal;  a  steam-pump  is  fed  with  coal.  The  one  carries 
the  mail,  and  the  other  keeps  a  mine  from  being  flooded.  Wherein 
lies  the  difference  of  action  ?  Clearl}^  in  the  build,  the  structure  of 
the  mechanism,  which  determines  the  manner  in  which  energy  shall 
be  transformed  within  it,  not  in  any  difference  in  the  source  of  the 
energy.  So  one  animal  cell,  whiii  it  is  stimulated,  shortens  or  con- 
tracts; another,  fed  perhaps  with  the  same  food,  selects  certain 
constituents  from  the  blood  or  lymph,  and  passes  them  through  its 
substance,  changing  them,  it  may  be,  on  the  way;  and  a  third  sets 
up  impulses  which,  when  transmitted  to  the  other  two,  initiate  the 
contraction  or  secretion.  In  the  living  body  the  cell  is  the  machine ; 
the  transformation  of  the  energy  of  the  food  is  the  process  which 
'  runs  '  it.  The  structure  and  arrangement  of  cells  and  the  steps 
by  which  energy  is  transformed  within  them  sum  up  the  whole  of 
biology. 

PRACTICAL  EXERCISES  ON  CHAPTER  I. 
Reactions  of  Proteins. 

I.  General  Reactions  of  Proteins.— Egg-albumin  may  be  taken  as  a 
type.  Prepare  a  solution  of  it  by  adding  water  to  white  of  e^g,  which 
consists  mainly  of  egg-albumin  with  a  little  globulin.  In  breaking  the 
egg,  take  care  that  none  of  the  yolk  gets  mixed  with  the  white.  Snip 
the  white  up  with  scissors  in  a  large  capsule,  then  add  ten  or  fifteen 
times  its  volume  of  distilled  water.  The  solution  becomes  turbid  from 
the  precipitation  of  traces  of  globulin,  since  globulins  are  insoluble  in 
distilled  water.  Stir  thoroughly,  strain  through  several  layers  of  muslin, 
and  then  filter  through  paper. 


INTRODUCTION 


Colour  Reactions. 


(i)  Add  to  a  little  of  the  solution  in  a  test-tube  a  few  drops  of  strong 
nitric  acid.  A  precipitate  is  thrown  down,  which  becomes  yellow  on 
boiling.  Cool,  and  add  strong  ammonia;  the  colour  changes  to  orange 
[xantho-proteic  reaction).  The  reaction  depends  upon  the  presence  of 
aromatic  groups  in  the  protein  (in  phenylalanin,  tyrosin,  tryptophane, 
oxylryptophane),  which  are  converted  into  nitro-compounds. 

(2)  To  a  third  portion  add  a  drop  or  two  of  very  dilute  cupric  sulphate 
and  excess  of  sodium  or  potassium  hydroxide ;  a  violet  colour  appears 
(Piotrowski's  test).  Peptones  and  proteoses  (albumoses)  give  a  pink 
(biuret  reaction) .*     See  p.  452. 

(3)  To  another  portion  add  Millon's  reagent  /f  a  white  precipitate 
comes  down,  which  is  turned  reddish  on  boiling.  If  only  traces  of 
protein  are  present,  no  precipitate  is  caused,  but  the  liquid  takes  on  a 
red  tinge.  The  reaction  is  due  to  tyrosin.  It  is  given  by  all  aromatic 
substances  which  contain  the  group  CgHg  with  at  least  one  H  replaced 
by  OH,  i.e.,  the  hydroxyphenyl  group  C(jH40H. 

(4)  Adamkiewicz's  Reaction  (Hopkins's  modification). — To  a  small 
quantity  of  the  albumin  solution  add  the  same  bulk  of  dilute  glyoxylic 
acid. J  Mix,  and  to  the  mixture  add  an  equal  volume  of  strong  pure 
sulphuric  acid.  A  purple  colour  is  obtained.  The  substance  in  the 
protein  molecule  which  gives  the  reaction  is  tryptophane  (p.  354). 

(5)  The  Formaldehyde  Reaction. — Add  to  the  albumin  solution  a  few 
drops  of  a  very  dilute  solution  of  formaldehyde  (i  :  2,500),  and  then 
allow  some  strong  (commercial)  sulphuric  acid  to  run  from  a  pipette 
into  the  bottom  of  the  test-tube.  A  purple  ring  appears  at  the  surface 
of  contact.  This  reaction  depends  on  the  presence  of  tryptophane  in 
the  protein. 

Precipitation  Reactions. 

(6)  Acidify  another  portion  strongly  with  acetic  acid,  and  add  a'few 
drops  of  a  solution  of  potassium  ferrocyanide.  A  white  precipitate  is 
obtained.     Peptones  do  not  give  this  reaction. 

(7)  Heat  a  portion  to  30°  C.  on  a  water-bath.  Saturate  with  crystals 
of  ammoniu:n  sulphate;  the  albumin  is  precipitated.  Filter,  and  test 
the  filtrate  for  proteins  by  (2).  None,  or  only  slight  traces,  will  be 
found.  The  sodium  hydroxide  must  be  added  in  more  than  sufficient 
quantity  to  decompose  all  the  ammonium  sulphate.  It  will  be  best  to 
add  a  piece  of  the  solid  hydroxide.  Peptones  are  not  precipitated  by 
ammonium  sulphate,  but  all  other  proteins  are. 

(8)  Add  alcohol  to  a  small  quantity  of  the  solution.     The  protein  is 

*  The  reaction  is  also  given,  although  more  faintly,  with  the  hydroxides  of 
lithium,  strontium,  and  barium.  It  is  given  by  all  substances  containing  at 
least  two  CONH2  groups  attached  to  one  another  (as  in  oxamide),  or  to  the 
nitrogen  atom  (as  in  biuret),  or  to  the  same  carbon  atom. 

f  Millon's  reagent  consists  of  a  mixture  of  the  nitrates  of  mercury  with 
nitric  acid  in  excess,  and  some  nitrous  acid.  To  make  it,  dissolve  mercury  in 
its  own  weight  of  strong  nitric  acid,  and  add  to  the  solution  thus  obtained 
twice  its  volume  of  water.  Let  it  stand  for  a  short  time,  and  then  decant  the 
clear  liquid,  which  is  the  reagent. 

X  A  solution  containing  glyoxylic  acid  in  the  requisite  strength  can  be 
prepared  by  treating  half  a  Htre  of  a  saturated  solution  of  oxalic  acid  with 
40  grammes  of  2  per  cent,  sodium  amalgam  in  a  tall  cylinder.  When  all  the 
hydrogen  has  been  evolved,  the  solution  is  filtered,  and  diluted  with  twice  its 
volume  of  water.  Oxalic  acid  and  sodium  binoxalate  are  also  present  in  the 
solution. 


PRACTICAL  EXERCISES  g 

precipitated.     It  can  be  redissolved  at  first,  but  rapidly  becomes  in- 
soluble. 

2.  Special  Reactions  of  Certain  Proteins — (i)  Heat-Coagulable  Pro- 
teins :  [a)  Albumins. — -(a)  Heat  a  little  of  the  solution  of  egg-albumin  in 
a  test-tube ;  it  coagulates.  With  another  sample  determine  the  tem- 
perature of  coagulation,  first  very  slightly  acidulating  with  a  2  per  cent, 
solution  of  acetic  acid. 

To  determine  the  Temperature  of  Coagulation. — Support  a  beaker  by 
a  ring  which  just  grips  it  at  the  rim.  Nearly  fill  the  beaker  with  water, 
and  slide  the  ring  on  the  stand  till  the  lower  part  of  the  beaker  is  im- 
mersed in  a  small  water-bath  (a  tin  can  will  do  quite  well).  In  this 
beaker  place  a  test-tube,  and  in  the  test-tube  a  thermometer,  both  sup- 
ported by  rings  or  clamps  attached  to  the  same  stand.  Put  into  the 
test-tube  at  least  enough  of  the  albumin  solution  to  .completely  cover 
the  bulb  of  the  thermometer,  and  heat  the  bath,  stirring  the  water  in 
the  beaker  occasionally  with  a  feather  or  a  splinter  of  wood,  or  a  glass 
rod,  the  end  of  which  is  guarded  with  a  piece  of  indiarubber  tubing. 
Note  the  temperature  at  which  the  solution  becomes  turbid,  and  then 
the  temperature  at  which  a  distinct  coagulum  or  precipitate  is  formed. 
Repeat  with  the  unacidulated  albumin  solution. 

(/3)  A  similar  experiment  may  be  performed  with  serum-albumin 
obtained  as  on  p.  65. 

{b)  Globulins. — U.se  serum-globulin  (p.  65),  or  myosinogen  (p.  793). 
Fibrinogen  is  also  a  globulin,  but  cannot  easily  be  obtained  in  quantity. 
Verify  the  following  properties  of  globulins: 
(a)  They  coagulate  on  heating. 
(/3)  They  are  insoluble  in  distilled  water  (p.  65). 
(y)  They  are  precipitated  by  saturation  with  magnesium  sulphate  or 
sodium  chloride  (p.  65). 

They  give  the  general  protein  tests  (i)  to  (8). 

Both  the  heat-coagulated  proteins  and  such  proteins  as  the  solid 
fibrin  which  is  formed  from  fibrinogen  in  the  clotting  of  blood  give  such 
of  the  general  protein  tests,  (i),  (2),  (3)  (p.  8),  as  with  suitable  modifica- 
tions can  be  instituted  on  solid  substances.  Thus,  in  performing  (2),  a 
flake  of  fibrin  or  a  small  piece  of  the  boiled  egg-white  should  be  soaked 
for  a  few  minutes  in  a  dilute  solution  of  cupric  sulphate.  Then  the 
excess  of  the  cupric  sulphate  should  be  poured  off,  and  sodium  hydroxide 
added,  when  the  coagulated  protein  will  become  violet.  Heat -coagu- 
lated proteins  are  insoluble  in  water,  weak  acids  and  alkalies,  and  saline 
solutions ;  fibrin  is  slightly  soluble  in  the  latter. 

(2)  Gelatin. — Add  some  pieces  of  gelatin  to  cold  water  in  a  test-tube. 
It  does  not  dissolve.  Immerse  the  tube  in  a  boiling  water-bath  till  the 
gelatin  goes  into  solution.  Then  cool  the  test-tube  under  the  tap;  the 
solution  sets  into  a  jelly.     On  heating  it  redissolves. 

Try  the  general  protein  reactions  (p.  8)  on  a  dilute  solution.  In 
Piotrowski's  test  a  violet  colour  is  obtained.  The  tests  which  depend 
on  the  presence  of  tyrosin  or  trj-ptophane  are  not  given  by  a  solution 
of  pure  gelatin,  since  these  amino-acids  are  absent  from  the  gelatin 
molecule.  Commercial  gelatin  may  give  a  slight  reaction  due  to 
traces  of  other  proteins. 

3.  Reactions  of  Certain  Derivatives  of  Native  Proteins — (i)  Meta- 
Proteins  :  (a)  Acid-Albumin. — To  a  solution  of  egg-albumin  add  a  little 
04  per  cent,  hydrochloric  acid,  and  heat  to  about  body  temperature — 
say  40°  C. — for  a  few  minutes.  Acid-albumin  is  formed.  It  can  be 
produced  from  all  albumins  and  globulins  by  the  action  of  dilute  acid. 
Make  the  following  tests: 

(a)  Add  to  a  portion  of  the  solution  in  a  test-tube  a  few  drops  of  a 


lo  INTRODUCTION 

solution  of  litmus;  the  colour  becomes  red.  Now  add  drop  by  drop 
sodium  carbonate  or  dilute  sodium  hydroxide  solution  till  the  tint  just 
begins  to  change  to  blue.  A  precipitate  of  acid -albumin  is  thrown 
down.  Add  a  little  more  of  the  alkali,  and  the  precipitate  is  redissolved. 
It  can  be  again  brought  down  by  neutralizing  with  acid. 

(/3)  Heat  a  portion  of  the  solution  to  boiling;  no  precipitate  is  formed, 
(y)  Add  strong  nitric  acid ;  a  precipitate  appears,  which  dissolves  on 
heating,  and  the  liquid  becomes  yellow. 

[b)  Alkali-albumin. — To  a  solution  of  egg-albumin  add  a  little  sodium 
hydroxide,  and  heat  gently  for  a  few  minutes.  Alkali-albumin  is 
produced.  It  can  be  derived  by  similar  treatment  from  any  albumin 
or  globulin. 

(a)  Neutralize,  after  colouring  with  litmus  solution,  by  the  addition 
of  dilute  hydrochloric  or  acetic  acid.  Alkali-albumin  is  precipitated 
when  neutralization  has  been  reached.  It  is  redissolved  in  excess  of 
the  acid. 

0)  To  another  portion  of  the  solution  of  alkali-albumin  add  a  few 
drops  of  sodium  phosphate  solution,  then  litmus,  and  then  dilute  acid 
till  the  alkali-albumin  is  precipitated.  More  of  the  dilute  acid  should 
now  be  required  to  precipitate  the  alkali-albumin,  since  the  sodium 
phosphate  must  first  be  changed  into  acid  sodium  phosphate. 

(y)  On  heating  the  solution  of  alkali-albumin  there  is  no  coagulation. 
(2)  Proteoses. — For  preparation  and  reactions,  see  p.  452.  They 
differ  from  albumins  and  globulins  in  not  being  coagulated  by  heat,  and 
from  meta-proteins  in  not  being  precipitated  by  neutralization.  They 
are  soluble  (with  the  exception  of  hetero-albumose)  in  distilled  water, 
and  are  not  precipitated  by  saturation  of  their  solutions  with  mag- 
nesium sulphate  or  sodium  chloride.  Saturation  with  ammonium  sul- 
phate precipitates  them.  With  a  solution  of  '  commercial  peptone,' 
which  consists  chiefly  of  albumoses,  and  contains  only  a  little  true 
peptone,  perform  the  following  tests: 

(a)  Boil  the  slightly  acidulated  solution;  there  is  no  coagulation. 
()3)  Biuret  reaction,  p.  8. 

(7)  To  a  portion  of  the  solution  add  its  own  volume  of  saturated 
ammonium  sulphate  solution.  The  primary  albumoses  (proto-  and 
hetero-albumose)  are  precipitated.  Filter.  Add  a  drop  of  sulphuric 
acid  to  the  filtrate  and  saturate  it  with  ammonium  sulphate  crystals. 
The  secondary  or  deutero-albumoses  are  precipitated.  Filter.  The 
filtrate  still  contains  peptones.     Use  it  for  (3). 

(3)  Peptones. — For  preparation  and  tests,  see  p.  453.  They  differ 
from  heat-coagulable  proteins  and  meta-proteins  in  the  same  way  as 
proteoses,  and  they  differ  from  proteoses  in  not  being  precipitated  by 
ammonium  sulphate.  On  the  filtrate  from  (2)  perform  the  biuret  test, 
as  described  in  (7),  p.  8;  and  note  that  the  pink  colour  is  the  same  as 
that  given  by  proteoses. 

Carbo-Hydrates. 

I.  Glucose  or  Dextrose. — Make  a  solution  of  dextrose  in  water,  and 
apply  to  it  Trommer  's  test  for  reducing  sugar.  Put  some  of  the  dextrose 
solution  in  a  test-tube,  then  a  few  drops  of  cupric  sulphate,  and  then 
excess  of  sodium  or  potassium  hydroxide.  The  blue  precipitate  of 
cupric  hydroxide  which  is  first  thrown  down  is  immediately  dissolved 
in  the  presence  of  dextrose  and  many  other  organic  substances.  Now 
boil  the  blue  liquid,  and  a  yellow  or  red  precipitate  (cuprous  hydroxide 
or  oxide)  is  formed. 


PRACTICAL  EXERCISES  ii 

2.  Cane-Sugar. — Perform  Trommer's  test  with  a  sample  of  a  solution. 
A  blue  liquid  is  obtained,  which  is  not  changed  on  boiling.  Now  put 
the  rest  of  the  solution  in  a  fiask.  Add  ^^jth  of  its  bulk  of  strong  hydro- 
chloric acid,  and  boil  for  a  quarter  of  an  hour.  Again  perform  Trom- 
mer's test.  Remember  that  excess  of  alkali  must  be  present  after  the 
acid  is  neutralized.  The  test  now  shows  much  reducing  sugar.  The 
cane-sugar  has  been  '  inverted  ' — i.e.,  changed  into  a  mixture  of 
dextrose  and  levulosc. 

3.  Starch. — (i)  Cut  a  slice  from  a  well-washed  potato;  take  a  scraping 
from  it  with  a  knife,  and  examine  with  the  microscope.  Note  the  starch 
granules  with  their  concentric  markings,  using  a  small  diaphragm. 
Run  a  drop  of  dilute  iodine  solution  under  the  cover-slip,  and  observe 
that  the  granules  become  bluish.  Examine  also  with  a  polarization 
microscope.  (2)  Rub  up  a  little  starch  in  a  mortar  with  cold  water, 
then  add  boiling  water  and  stir  thoroughly.  Decant  into  a  capsule  or 
beaker,  and  boil  for  a  few  minutes.  After  the  liquid  has  cooled,  perform 
the  following  experiments: 

(a)  Add  a  few  drops  of  iodine  solution  to  a  little  of  the  thin  starch 
mucilage  in  a  test-tube.  A  blue  colour  is  produced,  which  disappears 
on  heating,  returns  on  cooling,  is  bleached  by  the  addition  of  a  little 
sodium  hydroxide,  and  restored  by  dilute  acid. 

(b)  Test  the  starch  solution  for  reducing  sugar  by  Trommer's  test. 
If  none  is  found,  boil  some  of  the  mucilage  with  a  little  dilute  sulphuric 
acid  in  a  flask  for  twenty  minutes,  and  again  perform  Trommer's  test. 
Abundance  of  reducing  sugar  will  now  be  present. 

4.  Dextrin. — Dissolve  some  dextrin  in  boiling  water.  Cool.  Add 
iodine  solution  to  a  portion :  u  reddish-brown  (port-wine)  colour  results, 
which  disappears  on  heating.  As  a  control,  the  same  amount  of  iodine 
should  be  added  to  an  equal  quantity  of  water  in  another  test-tube. 
The  colour  returns  on  cooling.  The  colour  is  also  bleached  by  alkali, 
restored  by  acid.  Excess  of  iodine  should  be  added  for  the  bleaching 
experiment  {i.e.,  more  than  enough  to  give  the  maximum  depth  of  tint). 
If  too  little  iodine  has  been  added,  there  maybe  no  restoration  of  the 
colour  by  the  acid.  The  addition  of  a  little  more  iodine  to  the  acid 
solution  will  then  cause  the  port-wine  colour  to  return,  and  this  may 
be  again  bleached  by  alkali,  and  will  now  be  restored  by  acid. 

5.  Glycogen. — See  p.  689. 

6.  Molisch  's  Test  for  Carbo-Hydrates. — ^This  is  a  general  test  for  carbo- 
hydrates. It  is  also  given  by  proteins  which  contain  a  carbo-hydrate 
group.  Put  a  drop  of  dextrose  solution  in  a  test-tube.  Add  a  drop 
of  a  10  per  cent,  solution  of  a-naphthol  in  methyl  alcohol,  and  then 
o"5  c.c.  of  water.  Then  cautiously  allow  i  c.c.  of  pure  concentrated 
sulphuiic  acid  to  run  under  the  mixture,  and  shake  gently.  A  violet  or 
reddish  colour  appears. 

Fats. 

1.  Take  a  little  lard  or  olive-oil,  and  observe  that  fat  is  soluble  in 
ether  or  warm  alcohol,  but  not  in  water.  Put  a  drop  of  the  ethereal 
solution  of  fat  on  a  piece  of  paper,  and  note  that  it  leaves  a  greasy  stain. 

2.  Put  a  little  alcohol  in  a  test-tube,  and  then  a  drop  of  phenol- 
phthalein  solution  and  a  drop  or  two  of  dilute  sodium  hydroxide  to  give 
the  solution  a  red  colour.  Add  a  few  drops  of  an  ethereal  solution  of 
the  lard  or  olive-oil.  If  the  red  colour  persists,  the  fat  is  neutral;  if  it 
disappears,  the  fat  contains  free  fatty  acids. 

3.  Saponification. — Melt  some  lard  in  a  porcelain  dish,  and  pour  it 


12  INTRODUCTION 

into  an  alcoholic  solution  of  potassium  hydroxide  previously  heated  on 
a  water-bath  nearly  to  boiling.  Mix  well,  and  keep  the  mixture  gently' 
boiling  on  the  bath  till  saponification  is  complete.  This  only  takes  a 
short  time.  Remove  a  little  of  the  soap  solution,  and  drop  it  into  dis- 
tilled water  in  a  test-tube.  If  unsaponified  fat  is  present,  it  will  rise  to 
the  top  as  drops  of  oil.  In  this  case  boiling  should  be  continued.  If 
all  the  fat  has  been  saponified,  the  soap  solution  will  mix  with  the 
water  and  no  oil-drops  will  separate. 

4.  Fatty  Acids. — Heat  some  20  per  cent,  sulphuric  acid  in  a  small 
flask  nearly  to  boiling,  and  drop  into  it  some  of  the  soap  obtained  in  3. 
The  fatty  acids  separate  out  and  rise  to  the  top  as  an  oily  layer.  Cool, 
skim  off  the  fatty  acid,  and  wash  it  with  distilled  water  till  the  wash- 
water  is  no  longer  acid. 

(a)  Dissolve  a  little  of  the  washed  fatty  acid  in  ether.  Add  a  few 
drops  of  an  alkaline  solution  of  phenolphthalein  to  a  few  c.c.  of  water 
in  a  test-tube.  Drop  into  this  the  ethereal  solution  of  fatty  acid.  The 
red  colour  is  discharged. 

(b)  Put  a  small  portion  of  the  fatty  acid  on  a  glass  slide  resting  on  a 
piece  of  white  paper.  Place  on  it  a  drop  or  two  of  a  i  per  cent,  solution 
of  osmic  acid  (osmium  tetroxide).  The  osmic  acid  is  reduced  to  a  lower 
oxide  (which  is  black)  by  the  action  of  oleic  acid  present  in  the  fatty 
acid  mixture,  which  abstracts  some  of  the  oxygen.  Any  fat  which 
contains  olein  or  oleic  acid,  as  body-fat  does,  is  therefore  blackened  by 
osmic  acid. 

(c)  Add  to  a  portion  of  the  fatty  acid  some  sodium  hydroxide  solution, 
and  warm.  Sodium  soap  is  formed.  Add  warm  water  and  shake  up. 
A  lather  is  produced.  Keep  the  soap  solution  for  6.  Keep  a  little  of 
the  fatty  acid  for  5  (6)  and  6  (6) . 

5.  Glycerin. — (a)  Add  to  a  little  glycerin  in  a  dry  test-tube  a  few 
crystals  of  potassium  bisulphate  (KHSO4),  and  heat  over  the  free  flame. 
Acrolein  is  given  ofi,  which  is  recognized  by  its  pungent  odour,  and  by 
blackening  a  piece  of  filter-paper  moistened  with  ammoniacal  silver 
nitrate  solution,  and  held  over  the  mouth  of  the  test-tube.  The  paper 
is  blackened  owing  to  the  reducing  action  of  the  vapour  on  the  silver 
nitrate. 

{b)  Repeat  this  test  with  lard,  and  with  a  portion  of  the  fatty  acid 
from  4.  Acrolein  will  be  given  off  by  the  lard  because  glycerin  is  con.- 
tained  in  neutral  fat,  but  not  by  the  fatty  acid  if  it  has  been  properly 
separated  from  the  glycerin. 

6.  Emulsification.—{a)  Take  three  test-tubes  and  label  them  A,  B, 
and  C.  Put  a  few  c.c.  of  water  in  A,  a  solution  of  soap  in  B,  and  a 
dilute  solution  of  sodium  carbonate  or  sodium  hydroxide  in  C.  To  each 
add  a  few  drops  of  fresh  olive-oil  and  shake .  An  emulsion  will  be  formed 
in  B,  but  not  in  A.  Probably  there  will  be  some  emulsification  in  C  also, 
owing  to  the  presence  in  the  oil  of  some  fatty  acid,  which  forms  soap 
with  the  alkali.  But  if  the  oil  is  free  from  fatty  acid,  no  emulsion  will 
be  formed. 

{b)  Repeat  (a)  with  rancid  olive-oil,  which  contains  much  fatty  acid, 
or  with  fresh  olive-oil  to  which  some  of  the  fatty  acid  obtained  in  4  has 
been  added.     A  good  emulsion  will  be  produced  in  C  as  well  as  in  B. 

7.  Melting-Point  of  Fat. — Put  into  a  very  narrow  test-tube  or  a  short 
piece  of  narrow  glass  tubing  some  finely  divided  mutton  fat,  freed,  as 
far  as  possible,  from  connective  tissue.  Fasten  the  test-tube  on  to  the 
bulb  of  a  thermometer  with  a  rubber  band,  and  immerse  the  ther- 
mometer and  tube  in  a  beaker  filled  with  water  and  standing  on  a  water- 
bath,  which  is  gradually  heated.  Observe  the  temperature  at  which 
the  fat  melts.     Repeat  the  experiment  with  hog's  lard  and  dog's  fat. 


PRACTICAL  EXERCISES  13 

SCHEME  FOR  TESTING  A  SOLUTION  FOR  THE  MORE  COMMON 
PROTEINS  AND  PROTEIN-DERIVATIVES,  AND  FOR  CARBO- 
HYDRATES 

1.  Note  the  reaction,  and  whether  the  liquid  is  coloured  or  colourless,  clear 
or  opalescent.  A  reddish  colour  suggests  blood  ;  opalescence  suggests  glyco- 
gen or  starch.  Try  one  or  more  of  the  general  protein  tests  {e.g.,  the  xantho- 
proteic or  biuret).  If  the  result  is  positive,  proceed  as  in  2;  if  negative,  paiss 
to  3. 

2.  Test  for  Proteins. — (i)  If  the  reaction  is  acid  or  alkaline,  neutralize  with 
very  dilute  sodium  carbonate  or  sulphuric  acid.  A  precipitate = acid-  or 
alkali-albumin,  according  as  the  original  reaction  is  acid  or  alkaline.  If  the 
original  reaction  is  neutral,  no  acid-  or  alkali-albumin  can  be  present  in 
solution.     Filter  off  the  precipitate,  if  any. 

(2)  Boil  some  of  the  filtrate  from  (i)  (or  some  of  the  original  solution  if 
it  is  neutral),  acidulating  slightly  with  dilute  acetic  acid.  A  precipitate  = 
albumin  or  globulin.     Filter,  and  keep  the  filtrate. 

(3)  If  a  precipitate  has  been  obtained  in  (2),  (a)  saturate  some  of  the  original 
solution  with  magnesium  sulphate,  or  half  saturate  it  with  ammonium  sulphate 
[i.e.,  add  to  it  an  equal  volume  of  saturated  ammonium  sulphate  solution). 
If  there  is  no  precipitate,  globulin  is  absent,  and  therefore  the  precipitate 
obtained  in  (2)  must  be  albumin.  A  precipitate  =  globulin.  But  albumin 
may  also  be  present  in  the  solution.  To  see  whether  this  is  so,  filter  off  the 
globulin  and  boil  the  filtrate  after  acidulation  with  acetic  acid.  A  precipitate 
=  albumin. 

(6)  Half  saturate  the  filtrate  from  (2)  with  ammonium  sulphate  (i.e.,  add  its 
own  volume  of  a  saturated  solution  of  the  salt).  A  precipitate  =  primary 
proteoses.     Filter. 

(c)  Saturate  the  filtrate  from  (6)  with  ammonium  sulphate  crystals.  A 
precipitate  =  secondary  proteoses.     Filter. 

(d)  To  the  filtrate  from  (c)  add  excess  of  solid  sodium  hydroxide  in  small 
pieces  at  a  time.  Much  ammonia  is  given  off.  Allow  the  test-tube  to  stand 
fifteen  minutes,  shaking  it  at  intervals.  Then  add  dilute  cupric  sulphate, 
and  if  much  of  the  sodium  sulphate  formed  remains  undissolved,  add  water 
to  dissolve  it.     A  well-marked  rose  colour  =  peptone. 

(4)  If  no  precipitate  has  been  obtained  in  (2),  the  solution  contains  neither 
albumin  nor  globulin.  To  test  whether  primary  or  secondary  proteose  or 
peptone  is  present,  apply  (3)  (b),  (c),  and  (d). 

3.  Test  for  Carbo-Hydrates. — Use  the  original  solution,  freed  from  coagu- 
lable  proteins,  if  such  have  been  found,  by  acidulation  and  boiling. 

(i)  Add  iodine.  If  the  solution  is  alkaline  neutralize  it  before  adding  the 
iodine.  A  blue  colour  =  starch.  Confirm  by  boiling  with  dilute  sulphuric 
acid  and  testing  for  reducing  sugar.  A  reddish-brown  colour  with  iodine  = 
glycogen  or  dextrin. 

Glycogen  gives  an  opalescent,  dextrin  a  clear,  solution.  Glycogen  is  pre- 
cipitated by  basic  lead  acetate,  dextrin  is  not  (p.  689).  Both  are  changed 
into  reducing  sugar  by  boiling  with  dilute  acid. 

(2)  Add  to  some  of  the  original  solution  cupric  sulphate  and  excess  of 
sodium  hydroxide,  and  boil.     Yellow  or  red  precipitate  =reducing  sugar. 

(3)  If  (i)  and  (2)  are  negative,  boil  some  of  the  liquid  with  one-twentieth 
of  its  volume  of  strong  hydrochloric  acid  for  fifteen  minutes,  and  test  as  in  (2). 
A  red  or  yellow  precipitate  indicates  that  a  disaccharide  like  cane-sugar  was 
originally  present,  and  has  been  inverted. 


CHAPTER  II 
THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

In  the  living  cells  of  the  animal  body  chemical  changes  are  con- 
stantly going  on ;  energy,  on  the  whole,  is  running  down ;  complex 
substances  are  being  broken  up  into  simpler  combinations.  So  long 
as  life  lasts,  food  must  be  brought  to  the  tissues,  and  waste  products 
carried  away  from  them.  In  lowly  forms  like  the  amoeba  these 
functions  are  performed  by  interchange  at  the  surface  of  the 
animal  without  any  special  mechanism;  but  in  all  complex  organ- 
isms they  are  the  business  of  special  liquids,  which  circulate  in 
finely  branching  channels,  and  are  brought  into  close  relation  at 
various  parts  of  their  course  with  absorbing  organs,  with  eliminating 
organs,  and  with  the  tissue  elements  in  general. 

In  the  higher  animals  three  circulating  liquids  have  been  dis- 
tinguished: blood,  lymph,  and  chyle.  But  it  is  to  be  remarked 
that  chyle  is  only  lymph  derived  from  the  walls  of  the  alimentary 
canaJ,  and  therefore,  during  digestion,  containing  certain  freshly- 
absorbed  constituents  of  the  food;  while  both  ordinary  lymph  and 
chyle  ultimately  find  their  way  into  the  blood,  and  are  in  their  turn 
recruited  from  it.  The  blood  contains  at  one  time  or  another 
ever^'thing  which  is  about  to  become  part  of  the  tissues,  and  every- 
thing which  has  ceased  to  belong  to  them.  It  is  at  once  the 
scavenger  and  the  food-provider  of  the  cell.  But  no  bloodvessel 
enters  any  cell;*  and  if  we  could  unravel  the  complex  mass  of 
tissue  elements  which  essentially  constitute  what  we  call  an  organ, 
we  should  see  a  sheet  of  cells,  with  capillaries  in  very  close  relation 
to  them,  but  everywhere  separated  from  them  by  a  thin  layer  of 
lymph.  And  to  describe  in  a  word  the  circulation  of  the  food 
substances  we  may  say  that  the  blood  feeds  the  lymph,  and  the  lymph 
feeds  the  cell. 

Section  I. — Morphology  of  the  Blood. 

The  blood  consists  essentially  of  a  liquid  part,  the  plasma,  in 
which  are  suspended  cellular  elements,  the  corpuscles.  When  the 
circulation  in  a  frog's  web  or  lung  or  in  the  tail  of  a  tadpole  is 

*  Fine  intracellular  canaliculi,  communicating  with  the  blood-capillaries, 
and  probably  performing  a  nutritive  function,  since  they  seem  to  contain 
blood-plasma,  have  been  described  by  Schafer  and  others  in  the  liver  cells. 

14 


THE  BLOOD-CORPUSCLES  15 

examined  under  the  microscope,  the  bloodvessels  are  seen  to  be 
crowded  with  oval  bodies — of  a  yellowish  tinge  in  a  thin  layer,  but 
in  thick  layers  crimson — which  move  with  varying  velocity,  now 
in  single  file,  now  jostling  each  other  two  or  three  abreast,  as  they 
are  borne  along  in  the  axis  of  an  apparently  scanty  stream  of 
transparent  liquid.  Nearer  the  walls  of  the  vessels,  sometimes 
clinging  to  them  for  a  little  and  then  being  washed  away  again, 
may  be  seen,  especially  as  the  blood-flow  slackens,  a  few  com- 
paratively small,  round,  colourless  cells.  The  oval  bodies  are  the 
red  or  coloured  corpuscles,  or  erythrocytes;  the  colourless  elements 
are  the  white  blood-corpuscles,  or  leucocjrtes;  the  liquid  in  which 
they  float  is  the  plasma  (Practical  Exercises,  p.  191). 

The  Red  Blood-Corpuscles,  or  Erythrocytes,  differ  in  shape  and 
size  and  in  other  respects  in  different  animal  groups.  In  amphib- 
ians, such  as  the  frog  and  the  newt,  they  are  flattened  ellipsoids 
containing  a  nucleus,  and  the  same 

is  true  of  nearly  all  the  other  ver-  ^^^. Eltphant-       00^4. 

tebrates,    except     mammals.      In        /^^^^^N"  '  c^?  •*od5 

mammals  they  are  discs,  hollowed      //Z^^^S^X.'.'^'Aee/a         -ooso 
out  on  both  the  flat  surfaces,  or        \{({Cym\-\--t°^^t  .        ""*' 
biconcave,  and  possess  no  nucleus.       \  \N^=^x7  / 
But  the  red  corpuscles  of  the  Uama         \^^!]ril]^^ 

and    the     camel,     although    non- 

1      ,    J  n-        -J    1   •      ^u  Fig-   I- — Diagram  showing  Relative 

nucleated,  are  elhpsoidal  m  shape,  1^^^  ^^  r/^  Corpuscles  of  Various 

like  those  of  the  lower  vertebrates.        Animals. 

As  to  size,  the  average  diameter 

in  man  is  between  7  and  8  (.i*     In  the  frog  the  long  diameter  is 

about  22  fj,,  while  in  Proteus  it  is  as  much  as  60  fi,  and  in  Amphiuma, 

the  corpuscles  of  which  can  be  seen  with  the  naked  eye,  nearly 

80  iJb  {Frontispiece). 

As  regards  the  structure  of  the  red  corpuscles,  the  most  prob- 
able view  is  that  they  are  solid  bodies,  with  a  spongy  and  elastic 
structureless  framework,  denser  at  the  surface  of  the  corpuscle  than 
in  its  centre,  but  continuous  throughout  its  whole  mass  (Rollett). 
The  denser  peripheral  layer  constitutes  a  physiological  envelope 
which  permits  the  passage  of  certain  substances  into  or  out  of  the 
corpuscles,  and  hinders  the  passage  of  others.  In  the  large  oval 
corpuscles  of  Necturus  (see  Frontispiece)  the  envelope  can  be  clearly 
demonstrated  as  a  detachable  membrane  comparable  to  the  mem- 
brane surrounding  the  nucleus. 

Envelope  and  spongework  are  sometimes  spoken  of  as  the  stroma 
of  the  corpuscle,  in  contradistinction  to  its  most  important  con- 
stituent, a  highly  complex  pigment,  the  haemoglobin.  This  pigment 
is  not  in  solution  as  such,  for  its  solubility  is  not  nearly  great 
enough  to  permit  this,  but  either  in  solution  as  a  compound  with 
♦  A  micro-millimetre,  represented  by  symbol  ft,,  is  •nj'inr  millimetre. 


i6  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

some  other  unknown  substance,  or  more  probably  bound  in  some 
solid  or  semi-solid  combination  to  the  stroma,  and  filling  up  the 
space  within  the  envelope  in  the  interstices  of  the  spongework 
Since  there  is  good  reason  to  believe  that  the  haemoglobin  as 
obtained  artificially  from  the  corpuscles  is  not  quite  the  same  sub- 
stance as  the  native  blood-pigment  within  them,  the  latter  is  some- 
times distinguished  by  a  separate  name — hsemochrome.  To  the 
physical  properties  of  the  stroma  it  is  usual  to  attribute  the  great 
elasticity  of  the  corpuscles — that  is,  the  power  of  recovering  their 
original  shape  after  distortion- — for  their  elasticity  is  in  no  wise 
impaired  by  the  removal  of  the  haemoglobin. 

Rouleaux  Formation. — When  blood  with  disc-shaped  corpuscles  is 
shed,  there  is  a  great  tendency  for  the  corpuscles  to  run  together  into 
groups  resembUng  rouleaux,  or  piles  of  coin.  No  satisfactory  explana- 
tion of  this  curious  fact  has  yet  been  given. 

Crenation  of  the  corpuscles,  a  condition  in  which  they  become 
studded  with  fine  projections,  is  caused  by  the  addition  of  moderately 
strong  salt  solution,  by  the  passage  of  shocks  of  electricity  at  high 
potential,  as  from  a  Leyden  jar,  or  by  simple  exposure  to  the  air.  Con- 
centrated saline  solutions,  which  aljstract  water  from  the  corpuscles 
and  cause  them  to  shrink,  make  the  colour  of  blood  a  brighter  red, 
because  more  light  is  now  reflected  from  the  crumpled  surfaces.  On 
the  other  hand,  the  addition  of  water  renders  the  corpuscles  spherical; 
more  of  the  light  passes  through  them,  less  is  reflected,  and  the  colour 
becomes  dark  crimson  {Frontispiece). 

The  White  Blood-Corpuscles,  or  Leucocytes. — The  red  corpuscles 
are  peculiar  to  blood.  The  white  corpuscles  may  be  looked  upon 
as  peripatetic  portions  of  the  mesoderm  (see  Chap.  XIX.),  and  some 
of  them  ought  not  in  strictness  to  be  called  blood-corpuscles.  They 
are  more  truly  body  corpuscles.     Similar  cells  are  found  in  many 

situations,  and  wan- 
der everywhere  in  the 
spaces  of  the  connec- 
tive tissue.  They  pass 
into  the  bloodvessels 
with  the  lymph,  and 
may  pass  out  of  them 
again  in  virtue  of 
their  amoeboid  power. 
They  consist  of  proto- 

Fig.  2.— Amoeboid  Movement.     A,  B,  C,  D.  succes-        pl^sm,       less       differ- 
sive  changes  in  the  form  of  an  amoeba.  entiated      than      that 

of  any  other  cells  in 
the  body,  and  under  the  microscope  appear  as  granular,  colour- 
less, transparent  bodies,  spherical  in  form  when  at  rest,  and 
containing  a  nucleus,  often  tri-  or  multi-lobed.  Many  of  the  ieuco 
cytes  of  frog's  blood  at  the  ordinary  temperature,  and  of  mam- 
malian blood  when  artificially  heated  on  the  warm  stage,  may  be 


THE  BLOOD-CORPUSCLES  if 

seen  to  undergo  slow  changes  of  form.  Processes  called  pseudo- 
podia  are  pushed  out  at  one  portion  of  the  surface,  retracted  at 
another,  and  thus  the  corpuscle  gradually  moves  or  '  flows  '  from 
place  to  place,  and  envelopes  or  eats  up  substances,  such  as  grains 
of  carmine,  which  come  in  its  way.  This  kind  of  motion  was  first 
observed  in  the  amoeba,  and  is  therefore  called  amoeboid.  It  is 
perhaps  due  to  local  alterations  of  surface  tension;  at  any  rate, 
similar  phenomena  can  be  thus  produced  artificially.  The  leuco- 
cytes of  human  blood  are  not  all  of  the  same  size,  and  differ  also  in 
other  respects.  They  may  be  classified  according  to  the  presence 
or  absence  of  granules  in  their  protoplasm,  and  the  fineness  or 
coarseness  of  the  granules;  according  to  the  chemical  nature  of  the 
dyes  with  which  the  granules  most  readily  stain,  and  according  to 
the  form  of  the  nucleus.  Five  or  six  varieties  of  leucocytes  may 
thus  be  distinguished  in  normal  blood  {Frontispiece) : 

1.  Polymorphonuclear  Neutrophile  Cells. — The  nucleus  assumes  a 
great  variety  of  forms,  often  contorted  or  deeply  lobed,  the  lobes  being 
united  by  fine  strands  of  chromatin.  The  cytoplasm  contains  numerous 
fine  refractive  granules,  which  stain  best  neither  with  simple  acid  dyes 
like  eosin  nor  with  simple  basic  dyes  like  methylene  blue,  but  with 
mixtures  which  must  be  assumed  to  contain  '  neutral  '  stains,  like 
Ehrlich's  so-called  triacid  stain.*  These  cells  make  up  65  to  75  per 
cent,  of  the  total  number  of  leucocytes.  Their  diameter  is  10  to 
12  fi. 

2.  Eosinophih  Cells  (12  to  15  /*  in  diameter),  much  less  numerous  in 
normal  blood  than  the  neutrophiles  (less  than  5  per  cent,  of  the  whole), 
but  found  in  considerable  numbers  in  the  serous  cavities,  the  connec- 
tive tissue,  and  the  bone-marrow.  The  granules  in  the  cytoplasm  are 
coarser  than  the  neutrophile  granules,  and  stain  much  more  deeply 
with  eosin.  The  nucleus  may  be  simple,  lobed,  or  even  divided  into 
fragments  between  which  no  connection  can  be  traced.  It  is  less  rich 
in  chromatin,  and  stains  less  easily  with  basic  dyes,  like  methylene  blue, 
than  the  nucleus  of  the  first  variety. 

3.  Large  Mononuclear  (also  called  Transitional)  Leucocytes,  with  a 
diameter  of  12  to  15  /x.  They  possess  a  large  simple  or  slightly  lobed 
nucleus,  poor  in  chromatin,  surrounded  by  a  relatively  great  amount 
of  cytoplasm,  with  faint  neutrophile  granules — i.e.,  granules  which  stain 
with  neutral  dyes.  They  constitute  3  to  5  per  cent,  of  the  total  number 
of  leucocytes. 

4.  Lymphocytes  oj  Two  Varieties — (a)  Small  Lymphocytes. — Smaller 
cells  than  any  of  the  preceding  (diameter  6  p.),  possessing  a  single  large 
nucleus,  surrounded  by  a  comparatively  small  amoant  of  non-granular 
Cytoplasm;  20  to  25  per  cent,  of  the  leucocytes  of  the  blood  belong  to 
this  group.  The  lymphocytes  are  markedly  deficient  in  the  power  of 
amoeboid  motion  in  comparison  with  the  other  varieties  of  colourless 
corpuscles. 

(b)  Large  Lymphocytes. — The  largest  of  all  the  white  cells  of  the  blood, 
and  at  least  twice  as  large  as  the  small  lymphocytes.  They  possess 
a  relatively  great  proportion  of  cytoplasm,  which  is  devoid  of  granules. 
They  constitute  no  more  than  i  per  cent,  of  the  total  number  of  the 
colourless  corpuscles. 

•  A  mixture  of  orange  G.,  acid  fuchsin,  and  methyl  green. 

2 


I8  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

5.  '  Mast  Cells,'  or  '  Basophiles,'  the  least  numerous  variety  (o'5  per 
cent,  of  the  total  number).  Very  few  are  to  be  found  in  the  normal 
blood  of  adults,  but  more  in  children.  They  are  somewhat  smaller 
than  the  neutrophiles  (average  diameter  about  10  /x).  The  nucleus  is 
irregularly  trilobed.  The  protoplasm  shows  coarse  granules,  which  do 
not  glitter  like  the  granules  of  the  eosinophile  cells,  and  are  therefore 
less  conspicuous  in  the  unstained  condition.  Unlike  the  eosinophile 
granules,  they  stain  with  basic  dyes,  such  as  methylene  blue. 

Blood-Plates,  or  Thrombocytes.— When  blood  is  examined  im- 
mediately after  being  shed,  small  colourless  bodies  (i  to  3  //  in 
diameter)  of  various  shapes,  but  usually  round  or  oval,  may  be  seen. 
These  are  the  blood-plates  or  platelets,  also  called  thrombocytes, 
on  account  of  their  function  in  the  coagulation  of  blood.  If  the 
blood  is  not  at  once  subjected  to  some  procedure  which  prevents 
clotting,  the  platelets  swell  and  then  break  up.  There  is  reason  to 
believe  that  in  most  of  the  methods  of  preventing  coagulation  the 
essential  action  is  to  hinder  the  break-up  of  the  platelets  (p.  37). 
They  can  be  isolated  by  receiving  a  drop  of  blood  from  the  finger 
upon  a  well-cleaned  cover-slip,  which  is  then  laid,  supported  by  two 
thin  glass  fibres,  on  a  carefully  cleaned  slide.  The  plasma  with  the 
coloured  corpuscles  and  leucocytes  are  washed  away  by  irrigating 
the  space  between  slide  and  slip  with  a  suitable  solution,  e.g.,  a 
salt  solution  containing  a  certain  proportion  of  manganese  sulphate, 
which  prevents  disintegration  of  the  platelets.  The  platelets  stick 
to  the  cover-slip  (Deetjen).  They  can  then  be  fixed  and  stained. 
The  blood-plates  can  even,  like  leucocytes,  be  kept  alive  on 
the  warm  stage  in  an  appropriate  medium  (agar,  to  which  certain 
salts  have  been  added),  and  then  show  lively  amoeboid  movements 
(Deetjen).  They  have  been  described  as  nucleated  cells,  although 
the  nucleus  is  not  easy  to  stain,  and  with  the  ultra-microscope,  a 
delicate  means  of  testing  whether  such  an  object  as  a  platelet  is 
optically  homogeneous,  no  evidence  of  the  presence  of  a  nucleus 
has  been  obtained.  The  origin  of  the  platelets  has  been  a  matter  of 
lively  controversy.  They  are  not  produced  by  the  breaking  up  of 
other  elements  of  the  shed  blood,  for  they  have  been  observed 
within  the  freshly  excised,  and  therefore  still  living,  capillaries — 
in  the  mesentery  of  the  guinea-pig  and  rat  (Osier).  According  to 
the  best  evidence,  they  are  derivatives  neither  of  the  erythro- 
cytes nor  of  the  leucocytes  of  the  blood,  but  are  developed  from 
special  elements  (so-called  megakaryocytes)  of  the  blood-forming 
organs  (bone-marrow)  (J.  H.  Wright). 

Enumeration  of  the  Blood-Corpuscles. — This  is  done  by  taking  a 
measured  quantity  of  blood,  diluting  it  to  a  known  extent  with  a 
liquid  which  does  not  destroy  the  corpuscles,  and  counting  the 
number  in  a  given  volume  of  the  diluted  blood  (p.  67). 

The  average  number  of  red  corpuscles  in  a  cubic  millimetre  of 
blood  is  about  5,000,000  in  a  healthy  man,  and  about  4,500,000  in 


THE  BLOOD-CORPUSCLES 


19 


i.fJOL 


a  healthy  woman,  but  a  variation  of  1,000,000  up  or  down  can 
hardly  be  considered  abnormal.  In  persons  suffering  from  profound 
anaemia  the  number  may  sink  to  1,000,000  per  cubic  millimetre, 
or  even  less.     In  one  case  of  pernicious   anaemia,   only   143,000 

corpuscles  per  cubic  millimetre  were 
present,  the  lowest  number  recorded. 
In  new-bom  children  the  average  is 
over  6,000,000,  and  in  the  inhabi- 
tants of  high  plateaus  or  mountains 
it  may  rise  to  7,000,000,  or  even  more. 
Fig.  3.— Curve  showing  the  Number  In  the  latter  instance  a  residence  of  a 
of  Red  Corpuscles  at  Difierent  Ages  fortnight  in  the  rarefied  air  is  suffi- 
¥fe"..^rar„t  .hfirilTil  "<=nt  to  bring  about  the  increase,  and 
axis  are  years  of  age.  those  along  a  subsequent  residence  of  a  fortnight 
the  vertical  axis  millions  of  cor-  in  the  lowlands  to  annul  it.*  Over 
puscles  per  cubic  millimetre  of  ^3000,000  erythrocytes  to  the  Cubic 
blood.  .'   .  ,  •'  ,  -^  ,      . 

millimetre  have  been  counted  in 
a  case  of  cyanosis  (imperfect  oxygenation  of  the  blood,  with 
blueness  of  the  lips,  etc.),  due  to  congenital  disease  of  the 
heart. 

The  number  of  white  blood-corpuscles  is  on  the  average  about 
10,000  per  cubic  millimetre  of  blood, 
or  one  leucocyte  for  every  500  red 
blood-corpuscles.  But  if  the  count 
is  made  when  digestion  is  relatively 
inactive,  four  to  five  hours  after  a 
meal,  it  gives  no  more  than  7,000  to 
the  cubic  millimetre.  In  new-born 
children  the  average  number  is  over 
18,000  per  cubic  millimetre.  The 
total  leucocyte  count,  and  still  more 
the  so-called  differential  count,  i.e., 
the  determination  of  the  relative 
number  of  the  different  kinds  of 
leucocytes,  is  often  resorted  to  in 
the  study  of  pathological  condi- 
tions. A  distinct  increase  in  the 
number  is  designated  leucocytosis. 
In  leukaemia  the  number  of  white 
corpuscles  is  enormously  increased 
— on  the  average  to  about  300,000, 
600,000  per  cubic  millimetre 

♦  In  113  apparently  healthy  students  (male)  the  average  number  of  red 
corpuscles  was  5,190,000  per  cubic  millimetre.  In  104  of  these,  the  number 
ranged  from  4,000,000  to  6,400,000;  in  71  (or  63  per  cent,  of  the  whole),  from 
4,400,000  to  5,500,000;  in  3,  from  3,500,000  to  3,900,000;  in  5,  from  6,500,000 
to  7,000,000.     In  one  observation  the  number  reached  7,300,000. 


Fig.  4. — Curve  showing  Proportion 
of  White  Corpuscles  to  Red  at 
Different  Times  of  the  Day  (after 
the  Results  of  Hirt).  At  I  the 
morning  meal  was  taken;  at  If 
the  midday  meal;  at  III  the  even- 
ing meal.  During  active  digestion 
the  number  of  lymphocytes  in  the 
blood  is  greatly  increased,  both 
absolutely  and  relatively  to  the 
number  of  the  other  leucocytes. 

but    in  extreme   cases   to 
-while  at  the  same  time  the  number 


20  THE  CIJiCULATING  LIQUIDS  OF  THE  BODY 

of  the  red  corpuscles  is  diminished;  and  the  ratio  of  white  to  red 
may  approach  1:4.  As  the  anaemia  rapidly  advances  towards 
the  fatal  termination  of  an  acute  case,  and  the  erythrocyte  count 
falls  to  1,000,000,  or  even  less,  the  ratio  may  come  still  nearer  to 
unity.  An  increase  in  the  number  of  leucocytes  has  also  been  ob- 
served in  certain  infective  diseases  as  part  of  the  inflammatory 
reaction.  There  are  also  physiological  variations,  even  within  short 
periods  of  time;  for  exam^ple,  the  number  of  lymphocytes  is  in- 
creased when  digestion  is  going  on  (digestive  lymphocytosis).  The 
normal  number  of  blood-plates  varies  from  a  quarter  to  half  a 
million  to  the  cubic  millimetre,  but  may  be  greater  in  disease  and  at 
high  levels  (Kemp). 

Life-History  of  the  Corpuscles. — The  corpuscles  of  the  blood,  like 
the  body  itself,  fulfil  the  allotted  round  of  life,  and  then  die.  They 
arise,  perform  their  functions  for  a  time,  and  disappear.  But 
although  the  place  and  mode  of  their  origin,  the  seat  of  their  destruc- 
tion or  decay,  and  the  average  length  of  their  life,  have  been  the 
subject  of  active  research  and  still  more  active  discussion  for  many 
years,  much  yet  remains  unsettled. 

Origin  of  the  Erythrocytes. — In  the  embryo  the  red  corpuscles,  even 
of  those  forms  (mammals)  which  have  non-nucleated  corpuscles  in 
adult  life,  are  at  first  possessed  of  nuclei,  and  approximately  spherical 
in  form.  In  the  human  foetus,  at  the  fourth  week  all  the  red  corpuscles 
are  nucleated.  Later  on  the  nucleated  corpuscles  gradually  diminish 
in  number,  and  at  birth  they  have  almost  or  altogether  disappeared, 
some  of  them,  at  least,  having  been  converted  by  a  shrivelling  of  the 
nucleus  into  the  ordinary  non-nucleated  form.  In  the  newly  bom  rat, 
which  comes  into  the  world  in  a  comparatively  immature  state,  many 
of  the  red  corpuscles  may  be  seen  to  be  still  nucleated.  The  first  cor- 
puscles formed  in  embryonic  life  are  developed  outside  of  the  embryo 
altogether.  Even  before  the  heart  has  as  yet  begun  to  beat,  certain 
cells  of  the  mesoderm  (see  Chapter  XIX.)  in  a  zone  ('  vascular  area  ') 
around  the  growing  embryo  begin  to  sprout  into  long,  anastomosing 
processes,  which  afterwards  become  hollowed  out  to  form  capillary- 
bloodvessels.  At  the  same  time  clumps  of  nuclei,  formed  by  division 
of  the  original  nuclei  of  the  cells,  gather  at  the  nodes  of  the  network. 
Around  each  nucleus  clings  a  little  lump  of  protoplasm,  which  soon 
develops  haemoglobin  in  its  substance ;  and  the  new-made  corpuscles 
float  away  within  the  new-made  vessels,  where  they  rapidly  multiply 
by  mitosis.  In  later  embryonic  life  the  nucleated  corpuscles  continue 
in  part  to  be  developed  within  the  bloodvessels  in  the  liver,  allantois, 
spleen,  and  red  bone-marrow,  and  in  certain  localities  in  the  connective 
tissue,  by  mitotic  division  of  previously  existing  nucleated  corpuscles, 
in  part  to  be  formed  endogenously  within  special  cells  in  the  liver  and 
perhaps  other  organs.  Still  later  the  nucleated  corpuscles  give  place  in 
the  blood  of  the  mammal  to  non-nucleated  erythrocytes.  Many  of 
these  are  doubtless  derived  from  the  nucleated  corpuscles,  but  some 
appear  to  be  produced  in  the  interior  of  certain  cells  of  the  connective 
tissue,  and  are  non-nucleated  from  the  start. 

In  the  mammal  in  extra-uterine  life  the  chief  seat  of  formation 
of  the  red  blood-corpuscles,  or  haematopoiesis,  is  the  red  marrow  of 


THE  BLOOD-CORPUSCLES  ai 

the  bones  of  the  skull  and  tnink,  and  of  the  ends  of  the  long  bones 
of  the  limbs.  Special  nucleated  cells  in  the  marrow,  originally 
colourless,  multiply  by  karyokinesis,  take  up  haemoglobin  or,  what 
is  much  more  likely,  form  it  within  their  protoplasm,  and  are 
transformed  by  various  stages  into  the  ordinary  non-nucleated  red 
corpuscles,  which  then  pass  into  the  blood-stream.  These  blood- 
forming  cells  have  received  the  name  of  erythroblasts  or  hsemato- 
blasts.  According  to  their  size,  erythroblasts  have  been  distinguished 
as  normoblasts,  megaloblasts,  and  microblasts.  The  normo- 
blasts are  most  numerous,  and  have  about  the  same  diameter  as 
the  full-formed  erythrocytes,  into  which  they  are  believed  to 
develop.  The  megaloblasts  are  larger,  and  the  microblasts  smaller, 
and  they  are  thought  to  be  the  precursors  of  those  aberrant  forms 
of  erythrocytes  sometimes  found  in  the  blood  in  certain  diseases 
After  haemorrhage  rapid  regeneration  of  the  blood  takes  place,  so 
that  in  a  few  weeks  the  loss  of  even  as  much  as  a  third  of  the  total 
blood  is  made  good.  The  plasma  is  much  sooner  restored  to  its 
normal  amount  than  the  corpuscles.  Microscopical  examination 
shows  in  the  red  marrow  the  tokens  of  increased  production  of 
coloured  corpuscles,  and  nucleated  erythrocytes  appear  in  the 
blood,  the  normoblasts  being,  as  it  were,  hurried  into  the  circula- 
tion before  the  transformation  which  normally  results  in  the  dis- 
appearance of  the  nucleus  is  complete.  The  same  is  true  in 
severe  pathological  anaemias,  e.g.,  pernicious  anaemia.  It  is  a 
matter  of  interest  that  other  organs  also,  which  in  embr^^onic 
Hfe  perform  a  haematopoietic  function,  particularly  the  spleen, 
may,  in  such  emergencies,  again  take  on  the  office  of  forming 
blood-corpuscles. 

A  constant  destruction  of  red  blood-corpuscles  must  go  on,  for 
the  bile-pigment  and  the  pigments  of  the  urine  are  derived  from 
blood-pigment.  The  bile-pigment  is  formed  in  the  liver.  It  con- 
tains no  iron ;  but  the  liver  cells  are  rich  in  iron,  and  on  treatment 
with  hydrochloric  acid  and  potassium  ferrocvanide,  a  section  of 
liver  is  coloured  by  Prussian  blue.  Iron  must  therefore  be 
removed  by  the  liver  from  the  blood-pigment  or  from  one  of  its 
derivatives ;  and  there  is  other  evidence  that  the  liver  is  either  one 
of  the  places  in  which  red  corpuscles  are  actually  destroyed,  or 
receives  blood  charged  with  the  products  of  their  destruction. 
Although  it  cannot  be  doubted  that  in  all  animals  whose  blood 
contains  haemoglobin  the  iron  found  in  the  liver  bears  an  important 
relation  to  the  building  up  or  breaking  down  of  the  blood-pigment, 
the  injection  of  haemoglobin  or  haeniin,  indeed,  increasing  markedly 
the  amount  of  iron  in  the  liver,  as  well  as  in  the  spleen,  bone-marrow 
and  other  tissues,  this  does  not  seem  to  be  the  only  function  of  the 
hepatic  iron,  for  the  liver  of  the  crayfish  and  the  lobster,  which 
have  no  haemoglobin  in  their  blood,  is  rich  in  iron.     Destruction  of 


22  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

erythrocytes  may  also  take  place  in  the  spleen  and  bone-marrow. 
Although  the  statement  that  free  blood-pigment  exists  in  demon- 
strable amount  in  the  plasma  of  the  splenic  vein  is  incorrect,  red 
corpuscles  have  been  seen  in  various  stages  of  decomposition  within 
large  amoeboid  cells  in  the  splenic  pulp;  and  deposits  containing 
iron  have  been  found  there  and  in  the  red  bone-marrow  in  certain 
pathological  conditions.  But  there  is  no  good  foundation  for  the 
statement  sometimes  rather  fancifully  made  that  the  spleen  is  in 
any  special  sense  the  '  graveyard  of  the  red  corpuscles.'  Some  of 
the  coloured  corpuscles  may  break  up  in  the  blood  itself,  forming 
granules  of  pigment,  which  may  then  be  taken  up  by  the  liver,  spleen, 
and  lymph  glands.  Indeed,  it  is  probable  that  a  large  proportion 
of  the  worn-out  erythrocytes  are  finally  destroyed  in  the  blood- 
stream. The  portal  circulation  may  be  more  than  other  vascular 
tracts  a  seat  of  this  natural  decay,  perhaps  in  virtue  of  the  presence 
of  substances  with  a  hgemolytic  action  (p.  28)  absorbed  from  the 
alimentary  canal. 

It  has  been  argued  that  the  erythrocytes  must  be  short-lived, 
since  they  are  devoid  of  nuclei  (p.  6),  and  attempts  have  been 
made  to  calculate  the  average  time  for  which  they  survive  in  the 
circulation  from  the  amount  of  haemoglobin  (or  of  its  derivative, 
hgematin)  required  to  furnish  the  daily  excretion  of  bile-pigment. 
The  results  arrived  at,  however,  are  not  sufficiently  trustworthy  to 
warrant  their  citation. 

Origin  and  Fate  of  the  Leucocytes.— There  has  been  much  dis- 
cussion as  to  the  origin  of  the  white  blood-corpuscles.  The 
numerous  theories  fall  into  two  groups,  which  have  been  designated 
somewhat  pompously  the  monistic  and  the  dualistic.  According 
to  the  first,  all  the  colourless  corpuscles  arise  from  a  single  type 
of  parent  cell,  namely,  the  lymphocyte  type,  in  its  small  or  large 
variety.  According  to  the  dualistic  school,  a  fundamental  distinc- 
tion exists  between  the  lymphocytes,  or  cells  peculiar  to  lymphoid 
tissues,  and  to  the  blood  on  the  one  hand,  and  the  remaining  varieties 
of  leucocytes  on  the  other.  The  former  are  supposed  to  be  derived 
from  the  lymphoblasts  of  lymphoid  tissue,  and  the  latter  from  the 
myeloblasts,  the  forerunners  of  the  myelocytes  of  bone-marrow. 
The  question  has  recently  been  studied  by  Foot  by  a  new  method, 
namely,  by  cultivating  chicken  marrow  outside  of  the  body,  and 
watching  the  transformation  of  certain  of  its  cells.  He  concludes 
in  favour  of  the  development  of  the  polymorphonuclear  leucocyte 
from  a  lymphoid  type  of  cell  existing  in  the  marrow,  a  conclusion 
in  harmony  with  the  monistic  view.  As  regards  their  immediate 
source,  the  small  lymphocytes  of  the  blood  are  undoubtedly  derived 
from  the  lymph,  and  are  identical  with  the  lymph-corpuscles. 
That  they  are  formed  largely  in  the  lymphatic  glands  is  shown 
by  the  fact  that  the  lymph  coming  to  the  glands  is  much  poorer 


THE  BLOOD-CORPUSCLES  23 

in  corpuscles  than  that  which  leaves  them.  The  lymphatic  glands, 
however,  although  the  principal,  are  not  the  only  seat  of  formation 
of  lymphocytes,  for  lymph  contains  some  corpuscles  before  it  has 
passed  through  any  gland ;  and  although  a  certain  number  of  these 
may  have  found  their  way  by  diapedesis  from  the  blood,  others  are 
developed  in  the  diffuse  adenoid  tissue,  or  in  special  collections  of  it, 
such  as  the  thymus,  the  tonsils,  the  Peyer's  patches  and  soHtary 
follicles  of  the  intestine,  and  the  splenic  corpuscles.  To  a  very 
small  extent  white  blood-corpuscles  may  multiply  by  karyokinesis 
or  indirect  division  in  the  blood. 

The  fate  of  the  leucocytes  is  even  less  known  than  that  of  the 
red  corpuscles,  for  they  contain  no  characteristic  substance,  like 
the  blood-pigment,  by  which  their  destruction  may  be  traced.  That 
they  are  constantly  disappearing  is  certain,  for  they  are  constantly 
being  produced.  Not  a  few  of  them  actually  escape  from  the 
mucous  membranes  of  the  respiratory,  digestive,  and  urinary 
tracts.  The  remnants  of  broken-down  leucocytes  have  been  found 
in  the  spleen  and  lymph  glands.  It  must  be  assumed  that  many 
break  up  in  the  blood-plasma  itself. 


Section  II. — General  Physical  and  Chemical  Properties  of 

THE  Blood. 

Fresh  blood  varies  in  colour,  from  scarlet  in  the  arteries  to 
purple-red  in  the  veins.  It  is  a  somewhat  viscid  liquid,  with  a 
saline  taste  and  a  peculiar  odour. 

Viscosity  of  Blood.^ — The  viscosity  of  normal  dog's  blood  is  about 
six  times  greater  than  that  of  distilled  water  at  body  temperature. 
It  can  be  determined  by  allowing  the  blood  to  flow  through  a  capil- 
lary tube  of  known  dimensions  under  a  definite  pressure,  and 
measuring  the  amount  which  escapes  in  a  given  time.  In  general 
the  viscosity  and  specific  gravity  of  the  blood  vary  in  the  same 
direction,  although  there  is  not  an  exact  proportionality  between 
them.  Thus,  sweating,  which  causes  a  diminution  of  the  water  of 
the  blood,  causes  also  an  increase  in  its  viscosity.  With  increasing 
temperature  the  viscosity  of  the  blood  diminishes,  as  is  the  case 
with  other  liquids  (Burton-Opitz). 

In  polycythaemia,  where  the  number  of  erythrocytes  in  propor- 
tion to  plasma  is  greatly  increased,  the  viscosity  of  the  blood  in- 
creases in  an  equal  degree.  In  one  case  of  polycythsemia,  with  a 
blood-count  of  8,300,000,  the  viscosity  was  9-4  times  that  of  water; 
in  a  case  of  marked  chlorosis  it  was  only  2-14.  But  the  importance 
of  this  factor  in  causing  an  abnormal  blood-pressure  by  increasing 
or  diminishing  the  resistance  to  the  blood-flow  has  been  exaggerated. 
Although  it  has  been  shown  that  in  the  living  vessels,  so  long  as 


24  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

their  calibre  remains  constant,  the  flow  is  affected  by  changes  in 
the  viscosity  of  the  blood,  just  as  in  glass  tubes,  compensation  by 
adjustment  of  the  vascular  calibre  is  so  ample  and  so  easy  thai 
even  the  greatest  alterations  of  viscosity  produce  little  effect  on 
the  mean  blood-pressure. 

Reaction  of  Blood. — In  the  sense  in  which  the  term  is  used  in 
physical  chemistry,  the  reaction  of  a  solution  depends  on  the  pro- 
portion between  its  content  of  hydrogen  (H  -i- )  and  hydroxyl 
(OH  — )  ions,  an  excess  of  hydrogen  ions  corresponding  to  an  acid 
and  an  excess  of  hydroxyl  ions  to  an  alkaline  reaction.  It  has  been 
shown  by  a  physical  method  (the  determination  of  the  electro- 
motive force  of  a  cell  containing  blood  or  serum  as  one  liquid)  that 
hydroxyl  ions  are  present  only  in  small  excess,  and  that  blood  is 
really  but  a  little  more  alkaline  than  distilled  water.  Practically, 
it  may  be  regarded  as  a  neutral  Hquid.  Under  a  great  variety  of 
conditions,  physiological  and  pathological,  its  reaction  remains 
almost  unchanged.  Yet  it  is  known  that  acids  (carbon  dioxide, 
lactic,  phosphoric,  and  sulphuric  acids)  are  constantly  being  pro- 
duced in  the  normal  metabolism  of  the  tissues.  The  administra- 
tion of  large  quantities  of  acid  or  alkali  causes  a  surprisingly  small 
effect.  In  diabetes,  even  when  it  can  be  proved  that  an  abnormal 
production  of  acid  substances  is  taking  place,  the  blood  shows  little, 
if  any,  diminution  in  the  proportion  of  hydroxyl  ions;  it  remains 
to  all  intents  and  purposes  a  neutral  liquid.  In  diabetic  coma, 
where  the  blood  may  in  extreme  cases  turn  blue  litmus  red,  the 
true  reaction  is  only  slightly  altered. 

The  manner  in  which  the  reaction  of  the  blood,  the  tissue  liquids, 
and  probably  the  protoplasm  itself,  is  regulated  within  such  narrow 
limits  is  a  subject  of  great  interest.  For  there  is  reason  to  believe 
that  it  is  of  the  utmost  moment  that  the  equilibrium  should  be 
maintained  not  only  in  order  that  the  functions  of  the  tissues  may 
be  properly  performed,  but  that  danger  to  life  may  be  averted. 
To  be  sure,  the  excretory  organs,  the  lungs  and  the  kidneys,  provide 
the  means  by  which  the  excess  of  acid  (or  of  alkali)  is  finally,  under 
normal  circumstances,  eliminated.  Other  regulative  mechanisms 
also  exist.  For  example,  it  has  been  shown  that  when  an  excessive 
production  of  acids  (acidosis)  occurs  in  conditions  of  disordered 
metabolism,  or  when  acids  are  purposely  administered  in  large 
amount,  a  'grater  quantity  of  ammonia,  split  off  from  the  pro- 
teins, is  mobilized  to  aid  in  neutralizing  the  acids.  But  very 
simple  experiments  on  blood  in  vitro  are  sufficient  to  show  that 
the  blood  itself  has  a  great  capacity,  as  compared  with  water,  to 
resist  a  change  in  its  reaction  even  when  large  amounts  of  acid  or 
alkali  are  added  to  it.  The  secret  of  the  reaction-regulating  power 
lies,  therefore,  to  a  large  extent  in  the  blood  itself.  Two  factors 
have  been  shown  to  be  of  importance:  (i)  The  power  of  the  proteins, 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES         25 

in  virtue  of  their  amphoteric  character,  to  combine  either  with 
acids  or  with  bases,  so  that,  when  excess  of  base  is  added  to  blood, 
the  proteins  act  as  acids,  and  neutralize  the  base;  when  excess  of 
acid  is  added,  the  proteins  act  as  bases,  and  neutralize  the  acid. 
(2)  The  equilibrium  of  certain  of  the  inorganic  constituents  of  the 
blood  (carbon  dioxide,  the  carbonates,  and  the  phosphates)  is  such 
that  even  great  variations  in  the  concentration  of  any  of  these, 
such  as  may  normally  occur,  produce  scarcely  any  effect  upon  the 
concentrations  of  the  hydrogen  and  hydroxyl  ions. 

Thus,  when  phosphoric  acid  and  sodium  hydroxide  are  added  to 
water  in  certain  proportions,  and  the  solution  placed  under  a  certain 
tension  of  carbon  dioxide  (which  is  kept  constant),  we  get  a  more  or 
less  accurate  imitation  of  blood  as  regards  the  inorganic  substances 
concerned  in  the  regulation  of  its  reaction,  sodium  bicarbonate 
(NaHCOj)  and  disodium  phosphate  (Na2HP04)  being  present  in  the 
solution  as  in  blood.  It  is  found  that  wlien  the  quantities  are  so  chosen 
that  the  H  +  concentration  lies  within  the  limits  of  variation  of  the 
normal  blood  reaction,  relatively  large  quantities  of  alkalies  can  be 
added  or  withdrawn  without  causing  much  change  in  the  H  +  concen- 
tration. It  can  be  shown  both  theoretically  and  experimentally  that 
precisely  those  weak  acids  present  in  blood  (CO2,  NaH2P04)  require  the 
largest  addition  of  alkali  to  alter  the  reaction  to  a  given  extent,  and 
are  therefore  particularly  suited  to  give  stability  to  the  reaction. 
Thus  carbon  dioxide  requires  twenty-four  times,  and  monosodium 
phosphate  thirty-three  times,  as  much  alkali  as  an  equivalent  solution 
of  acetic  acid  to  cause  a  given  alteration  of  colour  in  rosolic  acid 
(E.  Henderson). 

The  so-called  '  titratable  '  alkalinity  of  blood  or  serum,  measured  by 
the  amount  of  standard  acid  which  must  be  added  before  the  colour  of 
the  indicator  used  changes  from  alkaline  to  acid,  bears  no  necessary  or 
fixed  proportion  to  the  actual  alkalinity.  When  blood,  for  instance, 
is  titrated  with  hydrochloric  acid,  with  methyl  orange  as  indicator,  at 
the  point  where  the  red  colour  appears  all  the  disodium  phosphate  and 
sodium  bicarbonate  will  have  been  changed  into  monosodium  phos- 
phate and  carbon  dioxide,  all  the  alkali  removed  from  combination 
with  proteins,  a  certain  amount  of  acid-protein  compounds  formed, 
and  other  minor  reactions  produced  (Henderson).  It  is  difficult  to 
correlate  the  quantity  deduced  from  such  a  titration  with  any  physio- 
logical condition,  although  undoubtedly  it  bears  some  relation  to  the 
acid-neutralizing  power  of  tlie  blood,  and  some  relation  to  its  real 
reaction.  Still,  by  titration  information  of  value  can  be  obtained 
which  is  not  yielded  by  the  physico-chemical  method  in  regard  to  the 
potential '  acid  capacity  '  of  the  blood  and  its  power  of  resistance  against 
acid-poisoning. 

What  is  estimated  here  is  the  quantity  of  acid  required  to  satisfy  the 
proteins  and  to  react  with  the  carbonates  and  phosphates  before  that 
concentration  of  hydrogen  and  hydroxyl  ions  just  necessary  to  cause 
the  change  of  colour  is  established.  This  is  not  tiie  same  for  different 
indicators,  since  there  is  a  certain  minimum  ratio  in  the  concentration 
of  these  ions  at  which  each  indicator  turns  in  one  or  the  other  direction, 
none  turning  precisely  at  the  neutral  point.  Tlius  serum  appears  to  be 
acid  when  tested  witli  phcnolphthalein,  and  alkali  must  be  added  to 
the  serum  before  the  pink  colour  indicating  alkalinity  is  produced. 
On  the  other  hand,  with  litnaus  or  methyl  orange  it  gives  the  alkaline 


26  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

reaction,  and  a  considerable  amount  of  acid  must  be  added  before  the 
colour  of  the  indicator  which  denotes  acidity  appears.  The  true  re- 
action of  the  serum  is  not,  of  course,  at  one  and  the  same  time  both 
alkaline  and  acid ;  but  it  is  so  near  neutrality  that  it  falls  just  below  the 
degree  of  alkalinity  necessarj^  to  give  the  pink  colour  with  phenol- 
phthalein,  and  just  below  the  degree  of  acidity  which  gives  the  pink 
colour  corresponding  to  an  acid  reaction  with  methyl  orange.  Certain 
indicators — for  example,  rosolic  acid — turn  so  as  to  give  sharp  colour 
reactions  at  about  the  concentration  of  hydrogen  and  hydroxyl  ions 
in  the  blood,  and  these  may  possibly  be  of  use  in  determining  the 
changes  in  the  true  reaction  for  clinical  purposes  (Adler). 

More  closely  related  to  the  true  alkalinity  of  the  blood  than  the 
titratable  alkalinity  is  the  carbon  dioxide  content.  The  estimation 
of  the  total  carbon  dioxide  in  a  sample  of  blood  throws  light  upon 
the  capacity  of  the  blood  to  perform  one  of  its  most  important 
functions — the  transportation  of  carbon  dioxide — and  to  preserve 
one  of  its  essential  properties — an  almost  neutral  reaction— in  the 
presence  of  an  excessive  intake  or  production  of  acid  substances. 
In  herbivorous  animals  the  carbon  dioxide  content  of  the  blood  is 
easily  lessened  by  the  administration  of  acids,  but  in  carnivora 
and  in  man  it  is  much  more  difficult  to  bring  about  such  a  decided 
effect,  for  the  reason  already  mentioned,  the  acid  being  neutralized 
by  ammonia.  In  many  diseases,  however,  and  particularly  in  those 
accompanied  by  fever,  this  protective  mechanism  breaks  down. 

Specific  Gravity  of  Blood. — The  average  specific  gravity  of  blood 
is  about  1066  at  birth.  It  falls  during  infancy  to  about  1050  in 
the  third  year,  then  rises  till  puberty  is  reached  to  about  1058  in 
males  (at  the  seventeenth  year),  and  1055  in  females  (at  the  four- 
teenth year).  It  remains  at  this  level  during  middle  life  in  males, 
but  falls  somewhat  in  females.  In  chlorotic  anaemia  of  young 
women  it  may  be  as  low  as  1030  or  1035.  It  rises  in  starvation. 
Sleep  and  regular  exercise  increase  it  (Lloyd  Jones).*  The  specific 
gravity  of  the  serum  or  plasma  varies  from  1026  to  1032. 

The  Electrical  Conductivity  of  Blood. — The  liquid  portion  of  the 
blood  conducts  the  current  entirely  by  means  of  the  electrolytes 
dissolved  in  it,  the  most  important  of  these  being  the  inorganic 
salts;  and  the  conductivity  of  the  serum  varies,  in  different  speci- 
mens of  blood,  within  a  comparatively  narrow  range.  The  con- 
ductivity of  entire  (defibrinated)  blood,  on  the  contrary,  varies 
within  wide  limits.  For  instance,  in  a  case  of  pernicious  anaemia 
the  conductivity  of  the  blood  was  found  to  be  almost  double  that 
of  normal  human  blood,  while  the  conductivity  of  the  serum  was 
normal.     The  most  influential  factor  which  governs  this  variation 

*  In  165  students  (male)  the  average  specific  gravity  of  the  blood,  as  deter- 
mined by  Hammerschlag's  method  (p.  62)  was  1054-4.  In  149  of  these  the 
variation  was  from  1050  to  1065;  in  94  (or  57  per  cent,  of  the  whole),  from 
1054  to  1060;  in  4,  from  1046  to  1049;  in  9,  from  1066  to  1070.  In  3  the 
specific  gravity  was  only  1040  to  1042. 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES         27 

is  the  relative  volume  of  the  corpuscles  and  serum.  When  the 
blood  is  relatively  rich  in  corpuscles  and  poor  in  serum,  its  con- 
ductivity is  low;  when  it  is  poor  in  corpuscles  and  rich  in  serum, 
its  conductivity  is  high.  The  explanation  is  that  the  corpuscle 
refuses  passage  to  the  ions  of  the  dissociated  molecules,  which,  in 
virtue  of  their  electrical  charges,  render  a  liquid  like  blood  a  con- 
ductor (p.  422),  or  permits  them  only  to  pass  very  slowly,  so  that 
the  intact  red  corpuscles  have  an  electrical  conductivity  so  many 
times  less  than  that  of  senim,  that  they  may,  in  comparison,  be 
looked  upon  as  non-conductors  (Practical  Exercises,  p.  69). 

The  Relative  Volume  of  Corpuscles  and  Plasma  in  Unclotted 
Blood,  or,  what  can  be  converted  into  this  by  a  small  correction, 
the  relative  volume  of  corpuscles  and  serum  in  defibrinated  blood, 
can  be  easily  determined,  with  approximate  accuracy,  by  com- 
paring the  electrical  conductivity  of  entire  blood  with  that  of  its 
serum.*  Another  method,  more  suitable  for  cHnical  work,  though 
not  so  accurate,  is  the  so-called  haematocrite  method.  A  small 
quantity  of  blood  is  centrifugalized  in  a  graduated  glass  tube  of 
narrow  bore  until  the  corpuscles  have  been  collected  into  a  solid 
'  thread  '  at  the  outer  extremity  of  the  tube.  Their  volume  and 
that  of  the  clear  plasma  which  has  been  separated  from  them  are 
then  read  off  on  the  scale.  The  haematocrite  must  rotate  at  such  a 
high  speed  (10,000  turns  a  minute)  that  separation  of  the  corpuscles 
from  the  plasma  is  accomplished  before  clotting  has  occurred. 
Dilution  of  the  blood  with  liquids  which  prevent  clotting  is  not 
permissible  for  exact  work  (Practical  Exercises,  p.  68).  By  these 
and  other  methods  too  elaborate  for  description  here,  it  has  been 
shown  that  the  plasma  or  serum  usually  makes  up  rather  less  than 
two-thirds,  and  the  corpuscles  rather  more  than  one-third,  of  the 
blood.  But  this  proportion  is,  of  course,  liable  to  the  same  varia- 
tions as  the  number  of  corpuscles  in  a  cubic  millimetre  of  blood. 
It  depends,  further,  the  number  of  corpuscles  being  given,  on  the 
average  volume  of  each  corpuscle.  For  instance,  when  the  mole- 
cular concentration,  and  therefore  the  osmotic  pressure  (p.  421), 
of  the  plasma  is  reduced,  as  by  the  addition  of  water  or  the  abstrac- 
tion of  salts,  water  passes  into  the  corpuscles  and  they  swell ;  .when 
the  molecular  concentration  of  the  plasma  is  increased,  by  the 
abstraction  of  water  or  the  addition  of  salts,  water  passes  out  of 
the  corpuscles,  and  they  shrink.     In  human  serum  the  average 

♦  The  formula^  ~h(\  (^74~  ■^(^))'  where  p  is  the  number  of  c.c.  of  serum 

in  100  c.c.  of  blood;  K{b),  K{s),  the  specific  conductivities  respectively  of  the 
blood  and  serum  (both  measured  at  or  reduced  to  5°  C,  and,  to  obtain  whole 
numbers,  multiplied  by  10*),  may  be  used  in  the  calculation.  K  is  the  specific 
conductivity  of  the  liquid — i.e.,  the  conductivity  of  a  cube  of  the  liquid  of 
I  centimetre  side.  The  conductivity  of  a  similar  cube  of  mercury  is  10,630. 
The  number  in  bracket.';  is  the  temperature  at  which  the  measurement  was 
made. 


28  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

depression  of  the  freezing-point  below  that  of  distilled  water,  which 
is  a  measure  of  the  molecular  concentration  and  of  the  osmotic 
pressure,  is  about  0-56°  C.  (Practical  Exercises,  p.  73).  For  clinical 
purposes,  the  determination  of  the  relative  volume  of  corpuscles  and 
plasma  is  most  useful  in  cases  where  the  average  size  of  the  er^^thro- 
cytes  departs  from  the  normal,  and  where,  accordingly,  the  enumera- 
tion of  the  corpuscles  would  give  an  erroneous  idea  of  their  total  mass. 

Laking  of  Blood,  or  Haemolysis. — Even  in  thin  layers  blood  is 
opaque,  owing  to  reflection  of  the  light  by  the  red  corpuscles.  It 
becomes  transparent  or  '  laky  '  when  by  any  means  the  pigment 
is  brought  out  of  the  corpuscles  and  goes  into  true  solution.  Re- 
peated freezing  and  thawing  of  the  blood,  the  addition  of  water, 
the  passage  of  electrical  currents,  constant  and  induced,*  putre- 
faction, heating  the  blood  to  60°  C,  and  many  chemical  agents  (as 
bile-salts,  ether,  saponin),  cause  this  change.  Certain  complex 
poisons  of  animal  origin,  such  as  snake- venoms,  bee-poison,  spider- 
poison  or  arachnolysin,  and  certain  toxins  produced  by  pathogenic 
bacteria — for  instance,  tetanolysin,  formed  by  the  tetanus  bacillus 
— also  possess  decided  hsemolytic  power.  The  blood-serum  of 
certain  animals  acts  on  the  coloured  corpuscles  of  others,  and  sets 
free  their  pigment — for  example,  the  serum  of  the  dog  or  ox  causes 
haemolysis  of  rabbit's  corpuscles;  the  serum  of  the  ox,  goat,  dog, 
or  rabbit  lakes  guinea-pig's  corpuscles.  But  rabbit's  serum  does 
not  lake  dog's  corpuscles,  and  guinea-pig's  serum  is  inactive  towards 
the  corpuscles  both  of  the  rabbit  and  the  dog.  It  has  been  shown 
that  in  haemolysis  by  foreign  serum  two  bodies  are  concerned:  one, 
which  is  easily  destroyed  by  heating  to  about  56°  C,  the  so-called 
complement,  and  another,  the  intermediary  body  or  amboceptor, 
which  is  not  affected  by  being  heated  to  this  temperature.  Thus 
if  dog's  serum  be  heated  to  56°  C.  for  twenty  minutes,  no  amount 
of  it  will  lake  rabbit's  washed  corpuscles — that  is,  rabbit's  corpuscles 
freed  from  their  own  serum  by  repeated  washing  with  salt  solution 
and  centrifugalization.  If,  however,  serum  which  is  not  itself 
hemolytic  for  rabbit's  blood  {e.g.,  rabbit's  or  guinea-pig's  serum) 
be  added  to  the  washed  rabbit's  corpuscles,  they  will  be  laked  by 
the  heated  dog's  serum.  Unheated  dog's  serum  will  lake  rabbit's 
corpuscles,  whether  they  have  been  washed  free  from  their  own 
serum  or  not  (Practical  Exercises,  p.  71). 

The  hypoth<rsis  which  best  explains  these  facts  and  many  similar 
ones  is  that  dog's  serum  contains  both  of  the  bodies  necessary  for 
haemolysis  of  rabbit's  corpuscles.  When  the  complement  has  been 
rendered  inactive  by  heating,  the  amboceptor  cannot  cause  laking 

•  The  laking  action  of  induced  currents  is  due  simply  to  the  heating  of  the 
blood.  Condenser  discharges,  which  cause  liberation  of  the  haemoglobin 
without  raising  the  temperature  of  the  blood  as  a  whole  to  the  point  at  which 
heat-laking  occurs,  possibly  act  in  the  same  way  by  causing  local  heating  ol 
the  corpuscles  owing  to  their  high  resistance. 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES         29 

by  itself.  Rabbit's  serum  contains  complement,  but  not  the 
specific  amboceptor  necessary  for  the  laking  of  rabbit's  corpuscles. 
Accordingly,  the  addition  of  fresh  rabbit's  serum  to  heated  dog's 
serum  restores  complement  to  the  latter,  and  thus  it  is  again  ren- 
dered active  for  rabbit's  corpuscles.  The  amboceptor  is  supposed 
to  unite  on  the  one  hand  with  certain  groups  in  the  corpuscle  and 
on  the  other  with  the  complement,  which  is  thus  enabled  to  develop 
its  haemolytic  action  upon  the  envelope  or  the  stroma.  The  com- 
plement is  incapable  of  acting,  even  in  the  presence  of  amboceptor, 
if  the  temperature  is  reduced  to  0°  C.  Neverth'eless,  the  corpuscles 
take  up  amboceptor  at  this  temperature,  and  on  this  fact  is  based 
a  method  of  freeing  serum  from  amboceptor.  For  example,  if 
dog's  serum  and  excess  of  rabbit's  washed  corpuscles,  both  pre- 
viously cooled  to  0°  C,  be  mixed  and  placed  at  0°  C  for  some  hours, 
and  the  serum  then  removed,  it  will  be  found  that  it  has  lost  the 
power  of  lakiing  rabbit's  corpuscles,  washed  or  unwashed,  at  air  or 
body  temperature,  although  it  will  still  do  so  on  the  addition  of 
dog's  serum  in  which  the  complement  has  been  destroyed  by 
heating  it  to  56°  C  The  real  nature  and  mode  of  action  of  com- 
plements and  amboceptors  are  not  yet  satisfactorily  determined. 
The  laws  of  chemical  equivalents  and  definite  proportions  do  not 
seem  to  be  observed  in  the  reactions  into  which  they  enter.  It  has 
therefore  been  suspected  that  the  bodies  in  question  belong  to  the 
group  of  ferments,  or  are  closely  related  thereto,  and  there  is  some 
evidence  that  a  fat-splitting  enzyme,  or  lipase,  is  concerned  in  the 
complement  action  (Jobling). 

As  to  the  manner  in  which  haemolytic  agents  cause  the  liberation  of 
the  blood-pigment,  the  fact  that  in  so  many  forms  of  laking  the  cor- 
puscles swell  up  before  the  haemoglobin  escapes  indicates  that  the 
entrance  of  water  is  an  important  step.  The  entrance  of  water  is 
favoured  by  changes  produced  in  the  chemical  and  physical  condition 
of  certain  constituents  of  the  superficial  layer  (envelope)  of  the  cor- 
puscle, as  well  as  by  changes  in  its  interior.  Saponin  and  ether,  for 
example,  are  known  to  be  solvents  of  cholesterin  and  lecithin,  and 
cholesterin  and  lecithin  are  important  constituents  of  the  stroma  and 
envelope  of  the  erj-throcyte.  It  is  easy  to  understand  that  if  a  portion 
of  one  or  both  of  these  substances  is  dissolved,  or  altered  without  being 
actually  dissolved,  profound  changes  may  be  produced  in  the  permea- 
bility of  the  corpuscle  to  water  and  to  the  salts  dissolved  in  the  liquid 
in  which  the  erythrocytes  are  suspended.  In  addition  to  this  change 
of  permeability,  many  laking  agents,  perhaps  all,  exert  also  a  more  direct 
influence  on  the  normal  relations  of  the  native  blood-pigment  to  the 
stroma.  Ether  and  saponin,  for  instance,  seem  to  act  in  two  ways — 
by  disorganizing  the  envelope  through  solution  of  its  lipoids,  and  thus 
increasing  its  pemacability  to  water;  and  by  helping  to  dissociate  the 
blood-pigment-stroma  complex  by  exerting  a  pull  on  the  lipoids  of  the 
stroma,  while  the  water  simultaneously  exerts  a  pull  on  the  pigment. 

The  conclusion  follows  from  this  view  of  haemolysis,  that  the  erythro- 
cytes, normally  so  perfectly  adapted  to  the  plasma  in  which  they  float, 
may,  when  the  conditions  on  which  their  equilibrium  with  it  depends 


30  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

are  altered,  be  rapidly  and  inevitably  destroyed  by  that  very  plasma 
itself.  It  is,  indeed,  the  ver^-  fact  of  the  exquisite  adaptation  of  liquid 
and  cell  for  a  strictly  regulated  exchange  of  material  which  constitutes 
the  danger  when  the  regulation  is  upset.  A  liquid  like  mercury,  which 
is  not  adapted  either  to  give  anything  to  erythrocytes  in  contact  with 
it  or  to  take  anj^i;hing  from  them,  would  not  cause  haemolysis,  even  if 
the  permeability  of  the  corpuscles  for  water  or  sodium  chloride  were 
increased  to  any  extent.  The  continued  survival  of  the  erythrocytes  in 
an  aqueous  solution  of  salts  and  proteins  like  the  plasma — nay,  more, 
the  protection  of  the  corpuscles  up  to  a  certain  point  by  the  plasma 
against  the  attack  of  extraneous  haemolytic  agents — are  facts  we  are 
prone  to  take  so  much  for  granted  as  to  forget  that  they  depend  entirely 
upon  a  most  delicate  adjustment  of  the  permeability  of  the  corpuscles 
for  essential  constituents  of  the  plasma.  Disturb  these  relations  to  a 
suf&cient  degree,  and  the  plasma  becomes  a  poison  to  the  erythrocytes 
not  much  less  deadly  than  distilled  water. 

When  we  add  to  blood  a  haemolytic  substance,  and  see  that  presently 
the  blood-pigment  has  left  the  corpuscles,  we  are  apt  to  attribute  the 
whole  effect  to  the  foreign  material  added,  and  to  say  that  the  saponin, 
the  ether,  the  alien  serum,  has  laked  the  blood.  In  a  certain  sense  this 
is  true,  but  it  is  not  the  whole  truth.  In  reality  the  haemolytic  agent 
has  acted  in  an  essential  degree,  although  not  exclusively,  by  overthrow- 
ing the  equilibrium  between  the  corpuscles  and  the  aqueous  solution 
of  certain  substances  in  which  they  are  suspended.  To  say  that  the 
foreign  substance  alone  causes  the  haemolysis  is  no  more  accurate  than 
it  would  be  to  say  that  a  man  swimming  strongly  in  a  rough  sea,  who 
sinks  when  hit  and  stunned  by  a  piece  of  wreckage,  was  drowned  by 
the  blow,  and  not  by  the  sea.  No  doubt  it  is  true  that,  but  for  the 
blow,  he  would  have  conlmued  to  swim;  yet,  in  reality,  he  loses  his  life 
because  he  is  environed  by  a  medium  deadly  to  him  as  soon  as  his  power 
of  adjustment  to  it  has  been  too  much  diminished.  On  land,  the  blow 
would  have  stunned,  but  would  not  have  killed  him.  In  like  manner, 
to  glance  at  one  phase  of  the  natural  decay  of  the  corpuscles  within  the 
body,  an  erythrocyte  may  float  secure  in  its  watery  environment 
through  many  rounds  of  the  circulation.  But  its  security  is  not  static, 
like  that  of  a  log  floating  on  the  water.  It  is  dynamic,  a  triumph  of 
perfect  physico-chemical  poise,  as  the  security  of  the  swimmer,  still 
more  of  the  tight-rope  dancer,  is  dynamic,  a  triumph  of  perfect  neuro- 
muscular poise.  The  time,  however,  arrives  when,  either  through 
changes  in  the  corpuscle  itself  (the  changes  of  cellular  senility,  as  we 
may  call  them),  or  through  changes  in  the  environing  medium,  or 
through  a  combination  of  the  two,  the  adjustment  is  upset,  and  the 
erythrocyte  is  now  destroyed  by  the  plasma  in  whiqh  it  has  so  long 
lived. 

In  general  hsemolysis  by  foreign  serum  is  preceded  by  agglutina- 
tion or  aggregation  of  the  corpuscles  into  groups.  Agglutination 
may  be  obtained  without  hsemolysis  by  heating  the  haemolytic 
serum  to  the  temperature  at  which  the  complement  is  destroyed, 
since  the  agglutinating  agents,  or  agglutinins,  are  relatively  resistant 
to  heat.  Besides  the  amboceptors  naturally  present  in  the  blood 
of  certain  animals,  and  capable,  in  conjunction  with  complement,  of 
haemolyzing  the  corpuscles  of  certain  other  animals,  amboceptors 
may  be  produced  in  much  greater  strength  by  artificial  means. 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES        31 

When  the  corpuscles  of  one  animal  are  injected  intraperitoneally 
or  subcutaneously  into  an  animal  of  a  different  kind,  the  serum  of 
the  latter  acquires  the  property  of  agglutinating  and  laking  the 
corpuscles  of  an  animal  of  the  same  kind  as  that  whose  corpuscles 
have  been  injected.  Ihis  is  especially  marked  if  the  injection  is 
several  times  repeated  at  intervals  of  a  few  days.  If,  for  instance, 
dog's  corpuscles  are  injected  into  a  rabbit,  the  rabbit's  serum  after 
a  time  becomes  strongly  haemolytic  for  dog's  corpuscles.  It  also 
agglutinates  them,  'ihis  is  due  to  the  appearance  in  the  rabbit's 
serum  of  an  amboceptor  and  an  agglutinin  which  have  a  specific 
action  on  dog's  corpuscles.  Such  a  serum  is  often  termed  an 
immune  serum,  and  the  animal  which  has  received  the  injections 
is  spoken  of  as  immunized  in  regard  to  this  particular  kind  of 
corpuscles.  For  the  reaction  involved  in  the  production  of  the 
amboceptor  and  agglutinin  is  a  particular  case  of  the  peculiar  and 
specific  response  which  the  body  makes  to  the  presence  of  foreign 
juices  or  cells,  including  bacteria,  and  which  constitutes  an  attempt 
to  render  itself  '  immune  '  to  them. 

Many  other  animal  cells  besides  the  coloured  blood-corpuscles  give 
rise,  when  injected,  to  similar  specific  substances  (cytolysins) ,  which 
cause  destruction  of  cells  of  the  same  kind — e.g.,  leucocytes  and 
spermatozoa.*  The  process  of  haemolysis  is  more  easily  followed 
than  the  cytolysis  of  ordinary  cells.  Yet  in  its  main  features  it  is 
essentially  similar. 

In  each  case  the  specific  antibody  seems  to  be  produced  in  response 
to  the  presence  of  some  particular  constituent  of  the  foreign  cell.  The 
substances  which  on  injection  give  rise  to  antibodies  are  spoken  of  as 
antigens.  In  the  case  of  the  erj^throcytes  there  is  evidence  that  the 
antigens  (both  the  haemolysinogen,  which  causes  the  production  of 
specific  amboceptor,  and  the  agglutininogen,  the  substance  which  gives 
rise  to  specific  agglutinin)  are  lipoids,  or  are  so  closely  associated  with 
the  lipoids  of  the  corpuscles  that  they  are  extracted  by  the  same  solvents. 
Thus  ethereal  extracts  of  erythrocytes  cause  the  production  of  haemol- 
ysin  and  agglutinin,  just  as  the  entire  corpuscles  do.  The  group  of 
antibodies  known  as  precipitins  is  of  special  interest. 

Precipitins. — When  the  serum  of  one  animal  is  injected  into 
another  of  a  different  group,  the  serum  of  the  latter  acquires  the 
property  of  causing  a  precipitate  in  the  normal  serum  of  animals 
of  the  same  group  as  that  whose  serum  was  injected,  but  not 

*  Recent  studies  have  tended  to  modify  the  view  that  the  cytotoxins 
formed  after  the  introduction  of  different  foreign  tissues  into  animals  are 
quite  specific  for  each  tissue.  Thus  Lambert,  using  tissues  cultivated  on 
media  outside  of  the  body  for  testing  the  toxic  action,  finds  that  the  plasma 
of  guinea-pigs  which  have  received  injections  of  either  chick  embryo  heart  or 
intestine  becomes  toxic  for  both  of  these  tissues.  In  like  manner  the  plasma 
of  guinea-pigs  treated  by  injection  of  rat  sarcoma,  a  tumour  which  can  be 
propagated  by  inoculation  in  rats,  acquires  a  toxic  action  on  cultures  of  both 
rat  sarcoma  and  the  skin  of  embryo  rats.  And  the  plasma  of  guinea-pigs 
treated  with  rat  embryo  skin  is  also  toxic  for  cells  of  both  types. 


32  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

in  the  serum  of  anv  other  kind  of  animal.  Thus,  if  human  blood 
or  serum  is  repeatedly  injected  at  short  intervals  into  a  rabbit,  the 
serum  of  the  rabbit  will  cause  a  precipitate  in  diluted  human  blood 
or  serum,  but  not  in  the  blood  or  serum  of  other  animals,  except 
that  of  monkeys,  where  a  slight  reaction  may  be  obtained.  The 
specific  bodies  which  cause  the  precipitation  are  termed  precipitins. 
The  phenomenon  has  been  made  the  basis  of  a  method  of  dis- 
tinguishing human  blood  for  forensic  purposes.  Other  animal 
fluids  and  solutions  containing  tissue  proteins  likewise  give  rise  to 
the  production  of  precipitins.  Thus,  when  cow's  milk  is  injected 
into  a  rabbit,  the  rabbit's  serum  acquires  the  power  of  precipitating 
the  caseinogen  of  cow's  milk.  Indeed,  the  response  of  the  animal 
body  to  the  presence  of  foreign  proteins  is  so  catholic,  and  at  the 
same  time  so  approximately  specific,  that  many  artificially  isolated 
proteins,  even  those  of  vegetable  origin,  after  as  careful  purifica- 
tion as  possible,  occasion,  when  injected,  the  production  of  anti- 
bodies which  will  precipitate  from  a  solution  only  the  variety  of 
protein  injected,  or  sometimes  also,  though  in  slighter  degree,  pro- 
teins nearly  related  to  it. 

Anaphylaxis. — Under  certain  conditions  the  injection  of  a  toxin,  a 
scrum,  or  a  protein  solution,  instead  of  eliciting  an  immunity  reaction 
which  tends  to  combat  the  effects  of  a  subsequent  injection  of  the  same 
material,  produces  the  opposite  result — namely,  a  sensitization  of  the 
animal  which  renders  the  second  dose  far  more  harmful  than  the  first. 
Thus,  Richct  found  that  animals  into  which  eel  serum,  or  the  poison 
contained  in  the  tentacles  of  Actinaria,  was  subcutaneously  introduced 
became  much  more  sensitive  to  the  toxic  action  of  a  second  injection. 
This  phenomenon  he  designated  anaphylaxis,  as  being  the  opposite  of 
the  prophylaxis  or  protection  afforded  by  previous  treatment  with  the 
toxins  hitherto  studied.  Later  on  it  was  discovered  that  the  sub- 
cutaneous injection  of  a  great  variety  of  proteins  alien  to  the  animal 
into  which  they  are  introduced  causes  anaphylaxis.  Only  very  minute 
amounts  are  necessary  for  the  first  or  sensitizing  dose,  and  an  interval 
considerably  greater  than  that  employed  in  the  production  of  an 
immune  serum  (p.  31)  is  allowed  to  elapse  before  the  second  injection 
is  made.  The  symptoms  induced  in  the  sensitized  animal  by  a  subse- 
quent dose  of  the  same  material  used  in  sensitization  differ  somewhat 
in  different  animals,  but  may  be  designated  in  general  terms  as  those 
of  collapse  or  shock  (anaphylactic  shock).  They  have  been  especially 
studied  in  the  rabbit  and  guinea-pig,  the  heart  being  particularly  affected 
in  the  former,  and  the  lungs  in  tlie  latter.  The  symptoms  are  very 
severe,  and  manifest  themselves  within  a  very  short  time  (a  few  minutes) 
of  the  injection.  A  large  proportion  of  the  animals  die.  If  an  animal 
recovers,  it  does  so  suddenly,  and  for  some  time  afterwards  it  is  in- 
sensitive to  the  particular  protein.  While  the  real  nature  of  protein 
sensitization  or  anaphylaxis  is  not  as  yet  understood,  it  affords  a  new 
and  delicate  test  for  the  detection  and  discrimination  of  proteins,  and 
has  already  been  utihzed  in  a  number  of  practical  applications.  For 
instance,  the  sophistication  of  sausages  with  other  than  the  orthodox 
ingredients — e.g.,  with  horseflesh — can  be  thus  exposed,  since  an  animal 
sensitized  by  horseflesh  will  exhibit  anaphylaxis  to  horseflesh,  but  not 
to  beef  or  pork.     In  like  manner,  the  anaphylactic  reaction  may  be 


GENERAL  PHYSICAL  AND  CHEMICAL  PROPERTIES         33 

use  J  for  the  identification  of  human  blood.  It  is  probable  that  an- 
aphylaxis plays  an  important  role  in  certain  pathological  reactions.  It 
is  well  known,  for  example,  that  some  persons  are  so  susceptible  to 
particular  foods  that  the  slightest  indulgence  in  them  brings  on  an 
attack  of  urticaria  or  nettlerash.  It  has  been  suggested  that  these 
persons  have  become  sensitized  to  certain  foreign  proteins — such  as 
those  existing  in  eggs,  veal,  pork,  strawberries,  shellfish,  or  whatever 
the  peccant  article  of  diet  may  be — possibly  by  absorption  at  some 
previous  time,  owing  to  gastro-intcstinal  disturbance,  of  small  quan- 
tities of  the  proteins  which  have  escaped  complete  digestion. 

It  is  only  when  proteins  are  introduced  parenterally  {i.e.,  by  some 
other  route  than  the  alimentary'  canal, «uch  as  the  subcutaneous  tissue, 
the  blood,  or  the  serous  cavities)  that  the  immunity  reactions  already 
described  and  the  phenomenon  of  anaphylaxis  can  be  experimentally 
produced.  For  in  digestion  the  protein  molecule  is  decomposed,  and 
although,  as  will  be  seen  later  on,  the  decomposition  products  are  not 
the  same  for  each  kind  of  protein,  the  factor  on  which  the  specificity 
of  the  molecule  depends  does  not  survive  the  hvdrolysis. 


Coagulation  of  the  Blood. 

Since  changes  begin  in  the  blood  as  soon  as  it  is  shed,  ha\-ing 
for  their  outcome  clotting  or  coagulation,  we  have  to  gather  from 
the  composition  of  the  stable  factors  of  clotted  blood,  or  of  blood 
which  has  been  artificially  prevented  from  clotting,  some  notion  of 
the  composition  of  the  unaltered  fluid  as  it  circulates  within  the 
vessels.  The  first  step,  therefore,  in  the  study  of  the  chemistry 
of  blood  is  the  study  of  coagulation. 

When  blood  is  shed,  its  viscidity  soon  begins  to  increase,  and 
after  an  interval,  varying  with  the  kind  of  blood,  the  temperature 
of  the  air,  and  other  conditions,  but  in  man  seldom  exceeding  ten, 
or  falling  below  three,  minutes,  it  sets  into  a  firm  jelly.  This  jelly 
gradually  shrinks  and  squeezes  out  a  straw-coloured  liquid,  the 
serum.  Under  the  microscope  the  serum  is  seen  to  contain  few  or 
no  red  corpuscles;  these  are  nearly  all  in  the  clot,  entangled  in  the 
meshes  of  a  kind  of  network  of  fine  fibrils  composed  of  fibrin.  In 
uncoagulated  blood  no  such  fibrils  are  present ;  they  have  accordingly 
been  formed  by  a  change  in  some  constituent  or  constituents  of 
the  normal  blood.  Now,  it  has  been  shown  that  there  exists  in  the 
plasma — *he  liquid  portion  of  unclotted  blood — a  substance  from 
which  fibrin  can  be  derived,  while  no  such  substance  is  present  in 
the  corpuscles.  In  various  ways  coagulation  can  be  prevented  or 
delayed,  and  the  plasma  separated  from  the  corpuscles.  For 
example,  the  blood  of  the  horse  clots  very  slowly,  and  a  low  tem- 
perature lessens  the  rapidity  of  coagulation  of  every  kind  of  blood. 
If  horse's  blood  is  run  into  a  vessel  surrounded  by  ice  and  allowed 
to  stand,  the  corpuscles,  being  of  greater  specific  gravity  than  the 
plasma,  gradually  sink  to  the  bottom,  and  the  clear  straw-yellow 
plasma  can  be  pipetted  off.     Or  the  addition  of  neutral  salts  to 

3 


34  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

blood  may  be  used  to  delay  coagulation,  the  blood  being  run  direct 
from  the  animal  into,  say,  a  third  of  its  volume  of  saturated  mag- 
nesium sulphate  solution.  The  plasma  may  then  be  conveniently 
separated  from  the  corpuscles  by  means  of  a  centrifugal  machine. 
Again,  two  ligatures  may  be  placed  on  a  large  bloodvessel,  so  that 
a  portion  of  it  can  be  excised  full  of  blood  and  suspended  vertically 
(the  so-called  experiment  of  the  '  living  test-tube  ') ;  coagulation 
is  long  delayed,  and  the  corpuscles  sink  to  the  lower  end.  In  these 
and  many  other  ways  plasma  free  from  corpuscles  can  be  got ;  and 
it  is  found  that  when  the  coniiitions  which  restrain  coagulation  are 
removed — -when,  for  instance,  the  temperature  of  the  horse's  plasma 
is  allowed  to  rise  or  the  magnesium  sulphate  plasma  is  diluted  with 
several  times  its  bulk  of  water — clotting  takes  place,  with  forma- 
tion of  fibrin  in  all  respects  similar  to  that  of  ordinary  blood-clot. 
The  corpuscles  themselves  cannot  form  a  clot.*  From  this  we  con- 
clude that  the  essential  process  in  coagulation  of  the  blood  is  the 
formation  of  fibrin  from  some  constituent  of  the  plasma,  and  that 
the  presence  of  corpuscles  in  ordinary  blood-clot  is  accidental. 
In  accordance  with  this  conclusion,  we  find  that  lymph  entirely 
free  from  red  corpuscles  clots  spontaneously,  with  formation  of 
fibrin ;  and  when  fibrin  is  removed  from  newly  shed  blood  by  whip- 
ping it  with  a  bundle  of  twigs  or  a  piece  of  wood,  it  will  no  longer 
coagulate,  although  all  the  corpuscles  are  still  there. 

What,  now,  is  the  substance  in  the  plasma  which  is  changed  into 
fibrin  when  blood  coagulates  ?  If  plasma,  obtained  in  any  of  the 
ways  described,  be  saturated  with  sodium  chloride,  a  precipitate  is 
thrown  down.  The  filtrate  separated  from  this  precipitate  does  not 
coagulate  on  dilution  with  water;  but  the  precipitate  itself — the 
so-called  plasmine  of  Denis — on  being  dissolved  in  a  little  water, 
does  form  a  clot.  Fibrin  is  therefore  derived  from  something  in 
this  precipitate.  Now,  '  plasmine '  contains  two  protein  bodies — 
fibrinogen,  which  coagulates  by  heat  at  about  56°  C,  and  serum- 
globulin,  which  coagulates  at  about  75°  C,  and  it  was  at  one  time 
believed  that  both  of  these  entered  into  the  formation  of  fibrin 
(Schmidt).  Hammersten,  however,  has  shown  that  fibrinogen  alone 
is  a  precursor  of  fibrin;  pure  serum-globulin  neither  helps  nor 
hinders  its  formation.  This  observer  isolated  fibrinogen  from  blood- 
plasma  by  adding  sodium  chloride  till  about  13  per  cent,  was 
present.  With  this  amount  the  fibrinogen  is  precipitated,  while 
serum-globulin  is  not  precipitated  till  20  per  cent,  of  salt  is  reached. 
After  precipitation  of  the  fibrinogen,  the  plasma  no  longer  coagu- 
lates; and  a  solution  of  pure  fibrinogen  can  be  made  to  clot  and 
to  form  fibrin,  while  a  solution  of  serum-globulin  cannot.     Blood- 

*  Bird's  corpuscles,  however,  washed  free  from  plasma,  will  form  a  clot 
when  laked  in  various  ways,  as  by  addition  of  water  or  by  freezing  and 
thnwing. 


COAGULATION  3S 

senim,  too,  which  contains  abundance  of  serum-globuHn,  but  no 
fibrinogen,  will  not  coagulate. 

So  far,  then,  we  have  reached  the  conclusion  that  fibrin  is  formed 
by  a  change  in  a  substance,  fibrinogen,  which  can  be  obtained  by 
certain  methods  from  blood-plasma.  It  may  be  added  that  there 
is  evidence  that  fibrinogen  exists  as  such  in  the  circulating  blood; 
for  if  unclotted  blood  be  suddenly  heated  to  about  56°  C,  the  tem- 
perature of  heat-coagulation  of  fibrinogen,  the  blood  for  ever  loses 
its  power  of  clotting.  The  liver  seems  to  be  an  important  place  of 
origin  of  fibrinogen,  which  may  also  be  formed  in  the  bone-marrow. 
That  the  liver  is  intimately  concerned  in  the  production  of  fibrinogen 
is  indicated  by  a  number  of  facts.  In  phosphorus  poisoning,  and 
notably  in  poisoning  by  chloroform,  which  causes  necrosis,  especially 
of  the  central  portions  of  the  hepatic  lobules,  the  amount  of 
fibrinogen  in  the  blood  is  quickly  diminished.  The  diminution  is 
proportional  to  the  extent  of  the  injury  to  the  liver,  and  the  blood 
loses  more  or  less  completely  its  power  of  clotting.  If  the  injury 
is  repaired,  the  fibrinogen  is  rapidly  regenerated  (Whipple).  If  the 
blood  is  allowed  to  circulate  for  a  time  in  the  head  and  thorax  of 
an  animal  without  passing  into  the  rest  of  the  animal's  body,  it 
becomes  incoagulable,  and  the  fibrinogen  is  found  to  be  markedly 
deficient  in  amount.  When  the  blood  of  an  animal  is  defibrinated 
by  whipping,  and  reinjected,  regeneration  of  the  fibrinogen  does 
not  occur  if  the  liver  has  been  eliminated,  whereas  it  takes  place 
rapidly  if  the  liver  is  intact  (Meek) . 

Since  fibrinogen  is  readily  soluble  in  dilute  saline  solutions,  and 
fibrin  only  soluble  with  great  difficulty,  we  may  say  that  in  coagu- 
lation of  the  blood  a  substance  soluble  in  the  plasma  passes  into  an 
insoluble  form.  How  is  this  change  determined  when  blood  is 
shed  ?  We  have  said  that  a  solution  of  pure  fibrinogen  can  be 
made  to  coagulate,  but  it  does  not  coagulate  of  itself.  1  he  addition 
of  another  substance  in  minute  quantity  is  necessary.  This  sub- 
stance, to  which  the  name  thrombin  has  been  applied,  can  be 
obtained  in  various  ways,  although  not  in  a  state  of  purity;  for 
example,  by  precipitating  blood-serum,  or  defibrinated  blood,  with 
fifteen  to  twenty  times  its  bulk  of  alcohol,  letting  the  whole  stand 
for  a  month  or  more,  and  then  extracting  the  precipitate  with 
water.  All  the  ordinary  proteins  of  the  blood  having  been  ren- 
dered insoluble  by  the  alcohol,  the  thrombin  passes  into  solution 
in  the  water,  and  the  addition  of  a  trace  of  the  extract  to  a  solution 
of  fibrinogen  causes  coagulation.  When  purified  as  well  as  possible, 
thrombin  still  gives  protein  reactions,  but  it  is  not  known  whether 
it  is  really  a  protein. 

The  action  of  thrombin  on  fibrinogen  helps  to  explain  many 
experiments  in  coagulation.  Thus,  transudations  like  hydrocele 
fluid  do  not  clot  spontaneously,  although  they  contain  fibrinogen, 


36  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

which  can  be  precipitated  from  them  by  a  stream  of  carbon  dioxide 
or  by  sodium  chloride.  But  the  addition  of  a  Httle  thrombin 
causes  hydrocele  fluid  to  coagulate.  So  does  the  addition  of  serum, 
not  because  of  the  serum-globulin  which  it  contains,  as  was  once 
believed,  but  because  of  the  thrombin  in  it.  The  addition  of  blood- 
clot,  either  before  or  after  the  corpuscles  have  been  washed  away, 
or  of  serum-globulin  obtained  from  serum,  also  causes  coagulation 
of  hydrocele  fluid,  and  for  a  similar  reason,  the  thrombin  having  a 
tendency  to  cling  to  everything  derived  from  a  liquid  containing 
it.  On  the  other  hand,  serum  which,  although  thrombi-n  is  present 
in  it,  does  not  of  itself  clot,  because  the  fibrinogen  has  all  been 
changed  into  fibrin  during  coagulation  of  the  blood,  can  be  made 
to  coagulate  by  the  addition  of  hydrocele  fluid,  which  oontains 
fibrinogen.  We  have  thus  arrived  a  step  farther  in  our  attempt  to  ex- 
plain the  coagulation  of  the  blood :  it  is  essentially  due  to  the  formation 
of  fibrin  from  the  fibrinogen  of  the  plasma  under  the  influence  of 
thrombin.  Up  to  this  point  there  is  agreement  between  physiologists. 
Some  difference  of  opinion  exists,  however,  as  to  the  mann^^r  in 
which  thrombin  is  formed  or  activated  when  blood  is  shed,  and  a? 
to  the  nature  of  its  action  upon  fibrinogen  once  it  is  fully  formed. 

The  Formation  of  Thrombin  from  its  Precursors.^ — ^There  is  good 
reason  to  believe  that  thrombin  is  formed  by  the  interaction  of  three 
factors:  (i)  A  substance  which,  since  it  is  a  precursor  of  thrombin, 
is  called  thrombogen,  or  prothrombin.  It  is  already  present  in  the 
circulating  plasma.  (2)  A  substance  liberated  from  the  formed  ele- 
ments of  the  shed  blood,  but  which  can  be  obtained  also  from  the 
cells  of  all  tissues.  Since  it  has  been  supposed  to  act  upon  throm- 
bogen, changing  it  into  fully  formed  thrombin,  much  in  the  same 
way  as  enterokinase  (p.  366)  acts  upon  trypsinogen,  changing  it 
into  fully  formed  trypsin,  it  is  called  thrombokinase  (Morawitz). 
(3)  Calcium  ions.  The  following  experiments  illustrate  the  role  of 
these  three  factors: 

The  plasma  obtained  by  drawing  off  bird's  blood — e.g.,  the  blood  of  a 
fowl  or  goose — through  a  perfectly  clean  cannula  into  a  perfectly  clean 
vessel,  without  contact  with  the  tissues,  and  then  rapidly  centrifugal- 
izing  off  the  formed  elements,  can  be  kept  unclotted  for  days  and  even 
weeks.  The  addition  of  a  small  amount  of  tissue  extract  (procured  by 
rubbing  up  blood-free  liver,  thymus,  muscle,  or  other  organs  with  sand, 
and  extracting  for  several  hours  with  salt  solution)  to  the  bird's  plasma 
causes  rapid  coagulation.  The  plasma  contains  thrombogen  and 
calcium  salts,  but  is  lacking  in  thrombokinase,  which  is  supplied  by  the 
tissue  extract.  A  solution  of  fibrinogen  containing  calcium  will  clot 
if  serum,  in  which  fibrin -ferment  is  always  present,  be  added.  It  will 
not  clot  on  addition  of  tissue-extract  alone,  nor  on  addition  of  bird's 
plasma  alone  (obtained  as  above),  but  will  readily  coagulate  if  both 
tissue  extract  and  bird's  plasma  be  added.  Therefore,  something  in 
the  bird's  plasma  (thrombogen),  plus  something  in  the  tissue  extract 
(thrombokmase),  produce  in  the  presence  of  calcium  the  same  effect  as 
the  thrombin  of  scrum.     It  can  be  shown  that  calcium  is  only  necessary 


COAGULATION  37 

for  the  formation  of  the  thrombin,  but  not  for  its  action  on  fibrinogen. 
For  instance,  a  calcium-free  solution  of  fibrinogen  can  be  made  to  clot 
by  serum  from  which  the  calcium  has  been  remov^ed. 

If  a  soluble  oxalate  (potassium  or  ammonium  oxalate)  is  mixed  with 
freshly  drawn  dog's  blood  to  the  amount  of  o'  2  or  o'  3  per  cent. ,  the  blood 
remains  unclotted.  The  plasma  separated  from  this  oxalatcd  blood 
contains  both  thrombogen  and  thrombokinase,  but  it  does  not  coagu- 
late, because  the  calcium  has  been  precipitated  out  in  the  form  of  in- 
soluble calcium  oxalate.  In  the  absence  of  calcium  the  reaction  of  the 
thrombogen  and  thrombokinase  which  leads  to  the  formation  of 
thrombin  does  not  take  place.  All  that  is  necessary  to  bring  about 
coagulation  is  to  add  calcium  chloride  in  somewhat  greater  quantity 
than  is  required  to  combine  with  any  excess  of  oxalate  present.  If  more 
than  a  certain  amount  of  calcium  be  added,  clotting  is  hindered  instead 
of  being  helped,  so  that  it  is  only  within  certain  limits  of  concentration 
that  calcium  favours  coagulation.  From  oxalate  plasma  a  nucleo- 
protein  or  a  mixture  of  nucleo-proteins  can  be  separated  which  contains 
thrombogen  and  thrombokinase,  but  little  or  no  calcium,  and  does  not 
cause  clotting,  but  which  on  treatment  with  a  calcium  salt  acquires  the 
properties  of  thrombin. 

When  sodium  fluoride  is  added  to  freshly  dra\\'Ti  blood  to  the  amount 
of  o'3  per  cent.,  coagulation  is  also  prevented.  But  there  is  this  differ- 
ence between  oxalate  and  fluoride  plasma — that,  although  the  calcium 
has  been  precipitated  in  both,  the  addition  of  calcium  chloride  to  fluoride 
plasma  is  not  suf&cient  to  induce  clotting.  Tissue  extract  containing 
thrombokinase  must  be  supplied  as  well.  In  some  way  or  other  sodium 
fluoride  interferes  with  the  liberation  of  thrombokinase  from  the  formed 
elements  of  the  blood,  although  in  the  concentration  mentioned  it  does 
not  hinder  the  action  of  fully  formed  thrombin,  as  is  shown  by  the  fact 
that  fluoride  plasma  coagulates  on  the  addition  of  a  little  serum,  which 
supplies  thrombin.  The  fluoride  blood  clots  readily  if  it  is  diluted  with 
water,  and  at  the  same  time  mixed  with  calcium  chloride  solution,  for 
the  water  damages  the  formed  elements,  and  thus  favours  the  liberation 
of  thrombokinase. 

Sodium  citrate  solution  prevents  the  coagulation  of  blood  run  into 
it,  although  there  is  no  precipitation  of  the  calcium.  The  addition  of 
calcium  chloride  to  citrate  plasma  induces  clotting,  and  the  action  of 
the  citrate  is  assumed  to  be  due  to  the  formation  of  a  compound  with 
the  calcium  of  the  blood,  which  does  not  dissociate  so  as  to  yield  calcium 
ions.  It  ought  to  be  remarked,  however,  that  in  all  so-called  decalci- 
fied plasmas,  as  ordinarily  obtained,  blood-platelets  are  present,  and 
that  platelets  disintegrate  under  the  influence  of  calcium  salts.  It 
has  been  shown,  indeed,  that  many  of  the  reagents  and  procedures 
which  hinder  the  clotting  of  shed  blood  also  prevent  the  breaking  up  of 
the  platelets.  Thus,  the  cooling  of  the  blood,  the  addition  of  hirudin, 
sodium  oxalate,  sodium  citrate,  manganese  salts,  etc.,  which  are 
classical  methods  used  in  obtaining  platelets  for  microscopical  study, 
are  also  classical  methods  of  hindering  coagulation.  These  facts  have 
not  hitherto  been  sufficiently  taken  account  of  in  interpreting  experi- 
ments on  decalcified  blood.  They  indicate  that  the  decalcifying  agents 
may  hinder  clotting  by  interfering  with  the  liberation  of  essential  sub- 
stances from  the  platelets,  and  that  this  may  be  the  decisive  factor,  and 
not  merely  the  withdrawal  of  the  calcium  from  the  field  where  the 
already  liberated  thrombokinase  and  thrombogen  would  othenvise 
react  to  form  thrombin. 

When  proteoses  (or  peptones)  are  injected  into  the  circulation  of  a 
dog  or  goose,  the  blood  is  deprived  of  the  power  of  coagulation.     The 


38  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

peptcne  plasma  must  be  assumed  to  contain  both  thrombogen  and 
thrombokinase,  since  it  can  be  made  to  clot  in  various  ways  {e.g.,  by  dilu- 
tion with  water  or  by  slight  acidulation  with  acetic  acid)  without  the 
addition  of  anything  which  could  supply  either  of  these  factors.  Yet 
a  little  tissue  extract  causes  it  to  clot  much  more  rapidly  than  simple 
dilution  or  acidulation,  and  more  rapidly  than  the  addition  of  serum. 
So  that  either  the  thrombokinase  already  present  in  peptone  plasma  is 
present  in  an  unavailable  form,  or  in  some  way  the  formation  of  throm- 
bin from  its  precursors  is  hindered.  But  this  is  not  the  only  cause  of 
the  incoagulability  of  peptone  plasma.  It  may  be  shown  to  contain 
an  antithrombin,  a  body  which  antagonizes  the  action  of  fully  formed 
thrombin,  and  which  does  not  seem  to  be  a  ferment,  since  it  acts  quan- 
titatively in  proportion  to  the  amount  present.  This  is  the  reason  why, 
although  peptone  plasma  can  always  be  made  to  clot  by  the  addition 
of  fibrin  ferment,  in  serum,  for  instance,  relatively  large  quantities  of 
it  must  be  supplied  (Practical  Exercises,  pp.  64,  65). 


Fig.  5. — Fibrin  Formation  in  Horse's  Plasma  (Ultrainicroscope)  (Stiibel).     Several 
clumps  of  disintegrated  platelets  from  which  the  fibrin  filaments  radiate. 

An  extract  of  the  head  of  the  medicinal  leech  in  salt  solution  prevents 
the  clotting  of  blood  both  in  the  test-tube  and  when  injected  into  the 
circulation.  The  plasma  obtained  differs  from  peptone  plasma  in 
refusing  to  coagulate  unless  tissue  extract  is  added.  It  is  therefore 
deficient  in  thrombokinase,  or,  rather,  as  has  been  shown,  the  kinase 

E resent  is  unable  to  act,  because  neutralized  by  antikinase  present  in  the 
;ech  extract.  Leech  extract  also  contains  an  antithrombin,  which  can 
be  neutralized  by  a  sufficient  amount  of  thrombin.  In  the  small 
wound  from  which  the  leech  sucks  blood  this  sufficient  amount  is  not 
present,  and  tlie  blood  remains  unclottcd,  as  it  also  does  in  the  alimen- 
tary canal  of  the  leech.  The  anticoagulant  substance,  hirudin,  has 
been  isolated,  and  gives  the  reactions  of  an  albumose. 

Sources  of  Thrombogen  and  Thrombokinase. — It  has  already  been 
stated  that  thrombogen  exists  in  the  circulating  plasma.  This  is 
shown  by  the  fact  that  fluoride  plasma  obtained  from  blood  drawn 
directly  through  a  wide  cannula  into  sodium  fluoride  solution,  with 


COAGULATION 


39 


all  precautions  to  prevent  alteration  of  the  blood,  and  immediately 
separated  from  the  formed  elements  by  the  centrifuge,  will  clot 
on  the  addition  of  tissue  extract.  The  source  of  the  thrombogen 
has  been  thought  to  be  the  blood-plates,  but  this  has  not  been 
proved.  Thrombokinase  is  not  present  in  the  circulating  plasma. 
In  shed  and  clotting  blood  which  has  not  been  allowed  to  come  into 
contact  with  cut  tissues,  the  only  possible  sources  of  thrombokinase, 
so  far  as  we  know,  are  the  corpuscles  and  the  blood-plates.  The 
red  corpuscles  we  may  at  once  dismiss,  for  although  the  stromata, 
especially  of  nucleated  corpuscles,  contain  thrombokinase,  or  can 
under  artificial  conditions  be  made  to  develop  that  action  on 
coagulation  by  which  we  recognize  its  presence,  not  only  do  they 
remain  intact  under  ordinary  circumstances  during  coagulation, 
but  there  is  strong  evidence,  as 
has  already  been  pointed  out, 
that  they  do  not  make  any  essen- 
tial contribution  to  the  process. 
We  have  left  over  the  leucocytes 
and  the  platelets,  and  it  is  highly 
probable  that  from  the  platelets 
thrombokinase  is  liberated  in  the 
first  moments  after  blood  is 
drawn,  and,  actingon  the  throm- 
bogen already  present  in  the  plas- 
ma, changes  it  into  actual  throm- 
bin. This  surmise  is  strengthened 
by  the  fact  that  in  freshly  shed 
mammalian  blood  extensive  de- 
struction of  blood-plates  takes 
place.  Viewed  with  the  ultra- 
microscope,  the  blood-platelets, 
in  a  drop  of  clotting  plasma, 

which  are  at  first  homogeneous  in  appearance  (optically  empty), 
become  granular.  Then  the  platelets  begin  to  agglutinate  and 
swell  up,  and  the  agglutinated  platelets  are  transformed  into  clumps 
of  granules,  from  which  needles  of  fibrin  shoot  out.  Otlier  needles 
and  filaments  of  fibrin  form  in  contact  with  the  glass  or  free  in 
the  plasma,  and  soon  the  field  is  occupied  by  a  felt-work  of 
fibrin.  The  leucocytes  have  not  been  observed  to  be  related  to  the 
process,  at  least,  in  the  blood  of  mammals  (Stiibel).  It  is  true  that 
the  wliite  layer  or  '  buffy  coat '  which  tops  the  tardily  formed  clot 
of  horse's  blood,  and  consists  of  the  lighter,  and  therefore  more 
slowly  sinking  colourless  cells,  causes  clotting  in  otherwise  in- 
coagulable liquids  like  hydrocele  fluid  much  more  readily  than  the 
red  portion  of  the  clot,  and  yields  far  more  thrombin  on  treatment 
with  alcohol.     It  can  also  be  easily  verified  that  in  mammalian 


Fig.  6. — Fibrin  Formation  in  Plasma  from 
a  Case  of  Haemophilia  (Ultramicro- 
scope)  (Stiibel).  The  needles  of  fibrin 
are  slowly  formed,  and  very  large. 


40  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

blood  collected  in  paraffined  vessels,  so  as  to  delay  clotting,  and 
immediately  centrifugalized,  coagulation  begins  in  and  around  the 
layer  of  white  elements,  and  then  spreads  upwards  in  the  stratum 
of  plasma  and  downwards  in  the  stratum  of  erythrocytes.  But  in 
this  white  upper  layer  platelets  are  always  intermingled  with  leuco- 
cytes. It  has  been  shown,  however,  that  the  blood  of  the  cray- 
fish, which  coagulates  with  extreme  rapidity,  contains  certain 
colourless  corpuscles,  which  immediately  it  is  withdrawn,  break 
up  with  explosive  suddenness,  and  that  substances  which  hinder 
the  breaking  up  of  these  corpuscles  restrain  coagulation  (Hardy). 
In  the  blood  of  another  crustacean  Limulus,  the  kingcrab,  coagula- 
tion is  preceded  by  an  agglutination  of  the  leucocytes  which  exhibit 
amoeboid  movements.  They  become  entangled  by  the  interlacing 
of  the  pseudopodia  which  they  protrude  (L.  Loeb). 

Thedisintegrationof  the  platelets  in  shed  blood  has  been  attributed 
by  Deetjen  to  an  increase  in  the  alkalinity  of  the  blood,  by  escape 
of  carbon  dioxide,  it  may  be.  When  blood  is  placed  on  a  quartz 
slide  and  covered  with  a  quartz  cover-slip,  the  platelets,  according 
to  this  observer,  do  not  break  up  ;  but  if  they  are  brought  into  con- 
tact with  a  medium  whose  OH  —  concentration  is  raised  ten  times 
or  more  above  that  of  freshly  drawn  blood  (still  only  a  weak  alka- 
line reaction),  disintegration  ensues.  He  supposes  that  the  contact 
of  glass  acts  harmfully  on  account  of  the  alkali  in  it.  It  is  im- 
possible to  say  at  present  whether  this  observation  has  any  bearing 
on  normal  coagulation. 

Thrombokinase  has  been  shown  to  exist  not  only  in  the  leuco- 
cytes, the  platelets,  and  the  stromata  of  the  coloured  corpuscles,  but, 
as  already  stated,  in  all  tissues  hitherto  examined.  Under  ordinary 
circumstances  it  appears  that  a  larger  amount  of  thrombogen  is 
liberated  or  is  already  present  in  shed  blood  than  can  be  changed 
into  thrombin  by  the  thrombokinase  set  free,  since  serum  contains 
a  surplus  of  thrombogen  in  addition  to  the  fully  formed  ferment. 
This  is  shown  by  the  fact  that  the  activity  of  a  given  quantity  of 
serum  in  causing  the  coagulation  of  a  plasma  not  spontaneously 
coagulable  or  of  a  fibrinogen  solution  is  increased  by  the  addition 
of  tissue  extract  (containing  thrombokinase). 

The  thrombin  of  any  particular  kind  of  vertebrate  blood  has  no 
marked  specific  action — that  is,  will  cause  coagulation  in  solutions  of 
fibrinogen  or  plasma  of  very  different  origin.  For  example,  the 
sera  of  all  vertebrates  hitherto  investigated  induce  clotting  in 
goose's  plasma.  On  the  other  hand,  it  appears  that  a  greater  degree 
of  specificity  exists  in  the  case  of  the  thrombokinase  and  throm- 
bogen, the  specificity  being  absolute  in  some  cases,  relative  in  others. 
That  is  to  say,  the  thrombokinase  of  one  animal  may  activate  the 
thrombogen  of  an  animal  of  another  group,  while  it  may  fail  to 
activate  the  thrombogen  of  an  animal  belonging  to  a  third  group. 


COAGULATION  4t 

But  it  will  always  activate  the  thrombogen  of  an  animal  of  the 
same  kind. 

To  sum  u-p,  we  may  say  that  when  blood  is  shed,  thrombin  is  rapidly 
formed  by  the  action  of  thrombokinase,  liberated  from  the  leucocytes, 
the  blood-plates,  and  possibly  to  some  extent  from  the  erythrocytes, 
upon  thrombogen,  already  present  in  the  circulating  plasma.  Further 
— and  this  is  of  great  practical  importance — since  no  vessel  is  opened 
under  ordinary  circumstances  except  through  a  wound  in  the  overly- 
ing structures,  the  cut  tissues  supply  a  store  of  thrombokinase  at 
the  point  where  it  is  required  to  aid  in  the  stanching  of  the  wound. 
Calcium  is  essential  to  the  reaction  by  which  thrombogen  and  thrombo- 
kinase form  thrombin,  but  is  not  necessary  for  that  action  of  thrombin 
on  fibrinoges  by  which  fibrin  is  produced  (Practical  Exercises, 
pp.  62-65). 

The  Nature  of  the  Action  of  Thrombin  on  Fibrinogen. — The  usual 
view,  first  advanced  by  Schmidt  many  years  ago,  is  that  thrombin 
acts  as  an  enzyme.  Hence  it  is  often  spoken  of  as  fibrin-ferment. 
In  support  of  this  theory  it  has  been  stated  that  the  thrombin 
does  not  itself  seem  to  be  used  up  in  the  process,  nor  to  enter  bodily 
into  the  fibrin  formed;  that  a  small  quantity  of  it  can  cause  an 
indefinitely  large  amount  of  fibrinogen  to  clot;  and  that  its  power 
is  abohshed  by  boiling  (p.  331).  There  has  been  a  disposition 
among  more  recent  observers  to  question  this  evidence.  Accord- 
ing to  Rettger,  the  quantity  of  fibrin  formed  when  a  small  amount  of 
thrombin  is  added  to  a  fibrinogen  solution  tends  to  a  fixed  maxi- 
mum, which  does  not  increase  with  the  time  of  action.*  Under 
certain  conditions,  also,  it  is  said  that  thrombin  is  not  destroyed  at 
the  temperature  of  boihng  water.  Whatever  the  precise  nature  of 
the  reaction  which  leads  to  the  precipitation  of  the  fibrinogen  in  the 
form  of  fibrils,  thrombin  is  very  loosely  combined  if  combined  at 
all  in  the  fibrin,  since  it  is  readily  extracted  by  an  8  per  cent, 
solution  of  sodium  chloride.  This,  indeed,  is  one  of  the  best  ways 
of  obtaining  an  active  thrombin  solution. 

The  view  which  we  have  followed  above,  in  accordance  with 
Morawitz,  that  the  substances  in  tissue  extracts  which  favour 
coagulation  do  so  by  activating  prothrombin  to  fully  formed 
thrombin,  has  also  been  opposed  by  a  number  of  the  more  recent 
workers.  Some  consider  that  they  exert  a  direct  action  upon 
fibrinogen  similar  to,  although  not  necessarily  identical  with,  that 
of  thrombin,  and  speak  of  them  as  coagulins  (L.  Loeb).  Howell 
holds  that  these  substances,  which  he  prefers  to  term  thrombo plastic 
substances,  since  this  makes  no  assumption  as  to  their  mode  of 
action,  play  a  quite  different  role,  namely,  that  of  neutralizing  anti- 
thrombin.     His  observations  have  led  him  to  the  conclusion  that 

*  The  inquiry  is  complicated  by  the  fact  that  fibrin,  once  formed,  tends  to 
adsorb  the  remaining  thrombin  and  so  to  interfere  with  its  further  action. 


42  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

the  effective  thromboplastic  substance  in  the  tissues  is  a  phos- 
phatide, probably  kephahn,  united  with  protein. 

Intravascular  Coagulation  Regulation  of  the  Clotting  Process, 
or  Thrombotaxis. — So  far  we  have  been  considering  the  problem 
of"  coagulation  as  if  all  the  data  for  its  solution  could  be 
obtained  by  a  study  of  the  blood  itself.  In  other  words,  our  main 
business  up  to  this  point  has  been  the  explanation  of  coagulation 
in  the  shed  blood;  it  has  been  only  incidentally,  and  with  the  object 
of  casting  light  on  the  question  of  extravascular  clotting,  that  we 
have  touched  on  the  coagulation  of  the  blood  within  the  living 
vessels.  It  is  not  possible  here  to  adequately  discuss,  nor  even  to 
define,  the  differences  between  the  two  problems.  All  we  can  do 
is  to  warn  the  student,  and  to  emphasize  the  warning  by  one  or 
two  illustrations,  that  valuable  as  is  the  knowledge  derived  from 
experiments  on  extravascular  coagulation,  it  would  be  totally  mis- 
leading if  applied  without  modification  to  the  circulating  blood. 
For  instance,  we  have  recognized  in  the  blood-plates  an  important 
source  of  the  thrombokinase  which  plays  so  great  a  part  in  the 
clotting  of  shed  blood;  but  we  may  be  sure  that  blood-plates  are 
constantly  breaking  down  in  the  lymph  and  the  blood,  and  we  have 
to  inquire  how  it  is  that  coagulation  does  not  occur,  except  in 
disease,  within  the  vessels.  Calcium  is  not  wanting  to  the  circu- 
lating plasma,  fibrinogen  is  not  wanting,  and  it  has  already  been 
mentioned  that  thrombogen  exists  in  perfectly  fresh  and,  as  we 
may  say,  still  hving  blood.  Why,  then,  does  it  not  coagulate  ? 
Some  have  said  that  coagulation  is  '  restrained  '  by  the  contact  of 
the  living  walls  of  the  bloodvessels;  but  although  it  is  certain  that 
the  contact  of  foreign  matter^ — and  all  dead  matter  is  foreign  to 
living  cells — does  hasten  the  destruction  of  blood-plates  or  that 
alteration  in  them  on  which  the  liberation  of  the  precursors  of  the 
ferment  depends,  it  is  evident  that  it  is  just  this  '  restraining  '  in- 
fluence of  the  vessels,  if  it  is  due  to  anything  more  than  the  mere 
smoothness  of  their  endothelial  lining,  which  has  to  be  explained. 
The  best  answer  which  can  be  given  to  the  question  is:  First,  that 
the  quantity  of  thrombokinase  free  in  the  plasma  at  any  given  time 
must  be  small,  since  no  evidence  of  its  presence  in  fluoride  plasma 
can  be  obtained.  If  thrombokinase  is  liberated  in  the  circulating 
blood,  we  may  assume  that  it  is  changed  into  some  inactive  sub- 
stance, or  quickly  eliminated.  And  it  appears  that,  unlike  the  true 
ferments,  thrombokinase  acts  quantitatively — i.e.,  in  proportion  to 
its  amount — upon  thrombogen.  Second,  an  antithrombin  exists 
in  the  circulating  plasma,  and  even  if  fully  formed  fibrin-ferment 
were  present,  it  could  not  cause  coagulation  until  the  antithrombin 
had  been  neutralized.  This  antithrombin  is  probably  not  manu- 
factured in  the  blood,  or  at  least  not  exclusively  in  the  blood,  but 
in  the  tissues,  and  there  is  no  reason  to  deny  the  vessels  themselves 


COAGULATION  43 

a  share  in  its  production,  even  if  its  presence  has  not  hitherto  been 
demonstrated  in  the  internal  coat  (L.  Loeb).  So  that  living  blood 
within  the  living  vessels  may  be  said  to  be  acted  upon  by  two  sets 
of  influences,  one  tending  to  favour  coagulation,  the  other  to  oppose 
it.  In  the  clotting  of  extravascular  plasma,  free  from  corpuscles, 
we  may  indeed  see  the  continuation,  under  modified  conditions,  of 
a  normal  process  always  going  on  within  the  bloodvessels.  Under 
normal  conditions,  the  processes  that  make  for  coagulation  never 
obtain  the  upper  hand. 

Indeed  the  margin  of  safety  within  which  what  may  be  called 
the  thrombo-regulative  mechanism  works  seems  to  be  surprisingly 
wide,  and  the  equilibrium  in  the  circulating  blood  far  more  stable 
than  observations  on  clotting  outside  of  the  body  might  lead  us  to 
suppose.  Very  considerable  quantities  of  thrombin  or  of  de- 
fibrinated  blood  or  serum  containing  thrombin  can  be  injected  into 
the  blood-stream  without  ill  effect.  According  to  Howell,  the 
presence  of  the  abnormally  great  amount  of  thrombin  causes  the 
formation  of  sufficient  antithrombin  to  neutralize  it,  probably  by  a 
protective  reflex  secretion.  In  like  manner  the  injection  of  tissue 
extracts  or  a  solution  ot  thrombo  plastic  substance  (thrombokinase) 
prepared  from  them  by  precipitation  does  not  necessarilv  induce 
coagulation  in  the  vessels.  On  the  contrary,  when  injected  slowly 
or  in  small  amount  into  the  veins  of  an  animal,  it  abolishes  for  a 
time  the  power  of  coagulation  of  the  blood;  and  when  this  '  nega- 
tive phase,'  as  it  is  called,  has  been  once  established,  even  a  very 
large  and  rapid  injection  produces  no  further  effect,  possibly  because 
an  antibody  which  neutralizes  the  action  of  thrombokinase  has 
been  produced.  In  both  cases  the  limits  of  safety  can  be  over- 
stepped, and  intravascular  clotting  induced  by  the  injection  either 
of  thrombin  or  of  thrombokinase.  When  a  considerable  quantity 
of  the  active  substance  in  tissue  extract  is  introduced  at  the  first 
injection,  extensive  coagulation  in  the  vessels  instantly  ensues;  the 
animal  dies  in  a  few  minutes;  and  the  right  side  of  the  heart,  the 
venae  cavae,  the  portal  vein,  and  perhaps  the  pulmonary  arteries, 
may  be  found  choked  with  thrombi.  Here  the  injected  thrombo- 
kinase is  responsible  for  the  clotting,  thrombogen  and  calcium  being 
already  present.  Curiously  enough,  intravascular  coagulation  fails 
to  be  produced  in  a  certain  proportion  of  cases  when  albino  animals 
are  injected  with  material  from  pigmented  animals,  while  there  is 
no  absolute  failure  of  coagulation  when  albinos  are  injected  with 
material  from  albinos,  and  no  failure  when  pigmented  animals  are 
injected  with  material  either  from  other  pigmented  animals  or  from 
albinos.  Intravascular  coagulation  on  injection  of  tissue  extracts 
is  especially  striking  in  birds. 

To  a  certain  extent  the  action  of  tissue  extracts  in  coagulation 
can  be  imitated  by  other  substances  of  animal  origin,  such  as  the 


44  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

venoms  of  some  vipers  (Martin).  It  is  not  known  whether  these 
substances  act  on  the  blood-plates,  leucocytes,  or  other  cells,  and 
thus  cause  an  increased  production  or  an  increased  liberation  of 
one  or  more  of  the  precursors  of  thrombin,  or  whether  they  take 
part  directly  in  its  formation.  But  there  is  some  evidence  that 
the  venoms  which  favour  coagulation  do  so  in  virtue  of  their  con- 
taining a  kinase.  On  the  other  hand,  cobra- venom  prevents  coagula- 
tion by  means  of  an  antikinase — that  is,  a  substance  which  antago- 
nizes the  action  of  kinase,  and  so  hinders  the  formation  of  thrombin. 
It  does  not  contain  an  antithrombin — that  is,  a  body  which  will 
prevent  the  action  of  thrombin  already  formed  (Mellanby). 

Relation  of  the  Liver  to  Coagulation. — It  is  not  known  with  any 
degree  of  certainty  whether  the  thrombo-regulative  processes  are 
especially  associated  with  any  particular  organ.     But  there  are 
facts  which  suggest  that  the  relations  of  the  liver  to  the  Coagulation 
of  the  blood  are  peculiarly  close.     Not  only,  as  previously  shown, 
does  it  take  an  important  share  in  the  formation  of  fibrinogen,  but 
there  is  some  evidence  that  it  is  closely  related  to  the  formation 
of  antithrombin.     We  have  already  mentioned  that  the  injection 
of  commercial  peptone,  which  consists  chiefly  of  proteoses,  into 
the  blood  of  dogs  causes  it  to  lose  its  coagulability.     The  effect 
gradually  passes  away,  till  after  some  hours  the  original  power  of 
coagulation  is  restored  (p.  63).     The  liver  is  known  to  be  intimately 
concerned  in  the  production  of  this  remarkable  result,  for  if  the 
circulation  through  it  be  interrupted,  the  injection  of  proteose  is 
ineffective.      Further,    if    a    solution    of    proteose    is    artificially 
circulated  through  an  excised  liver,  a  substance  (perhaps  an  anti- 
thrombin) is  formed  which  is  capable  of   suspending  the  coagula- 
tion of  blood  outside  of  the  body,  a  property  which  proteoses  them- 
selves do  not  possess,  or  possess  only  in  slight  degree.     It  is  not 
believed  that  the  proteose  is  actually  changed  into  this  anticoagu- 
lant substance,   but  rather  that  the  liver  cells  produce  it  as  a 
'  reaction  '  to  the  presence  of  the  foreign  substance,  being  perhaps 
stimulated  in  some  way  by  the  circulating  proteose.     In  part  the 
abnormally  great  alkalinity  of  the  peptone  blood,  due  to  the  excess 
of  alkali  secreted  by  the  liver,  is  responsible  for  its  slow  coagulation. 
Under  certain  conditions,  some  of  which  are  known  and  others  not, 
the  injection  even  of  one  or  other  of  the  purified  proteoses  causes 
not  retardation,  but  hastening,  of  coagulation ;  and  if  this  has  been 
the  result  of  a  first  injection,  a  second  is  equally  unsuccessful.     It 
is  possible  that  by  an  effort  of  the  organism  to  restore  the  normal 
coagulability  of  the  blood,  on  which  its  very  existence  depends, 
substances  which  favour  coagulation  are  produced,  and  that  the 
result  of  an  injection  of  proteose  is  determined  by  the  relative 
amount  of  coagulant  and  anticoagulant  secreted  in  a  given  time. 
Protamins  (products  obtained  from  the  ripe  milt  of  certain  fishes, 


COAGULATION  45 

and  believed  to  be  the  simplest  proteins)  exert,  when  injected 
intravenously,  a  retarding  influence  on  coagulation,  and  lower  the 
blood-pressure,  just  as  albumoses  do  (Thompson).  Even  serum- 
albumin  and  serum-globulin  possess  this  property  in  some  degree. 
All  these  substances  also  cause  a  diminution  in  the  number  of 
leucocytes  in  the  blood  owing,  in  the  case  of  albumose  at  any  rate, 
to  their  accumulation  in  the  abdominal  vessels,  and  not  to  any 
actual  destruction  of  them. 

It  has  been  lately  announced  that  the  adrenal  glands  have  a  relation 
to  the  coagulation  of  the  blood.  Stimulation  of  the  splanchnic  nerve, 
which  supplies  secretory  fibres  to  the  adrenal,  greatly  hastens  coagula- 
tion, but  has  no  such  effect  if  the  adrenal  on  the  corresponding  side 
has  been  previously  removed  (Cannon).  It  is  possible  that  this  effect 
is  exerted  through  the  liver,  since  it  is  known  that  one  important 
function  of  the  liver,  the  regulation  of  the  sugar  content  of  the  blood, 
is  intimately  dependent  upon  the  adrenal,  and  is  affected  by  excitation 
of  its  splanchnic  nerve-supply. 

In  certain  pathological  conditions  the  normal  balance  of  the  factors 
that  make  for  clotting  and  prevent  it  may  be  upset,  and  the  scales  may 
tip  in  either  direction.  In  patients  suffering  from  the  formation  of- 
spontaneous  clots  in  the  veins  (thrombosis)  it  is  stated  that  the  anti- 
thrombin  in  the  blood  is  diminished,  the  amount  of  prothrombin  being 
normal.  The  mere  slowing  of  the  blood-stream  in  conditions  where 
the  circulatory  mechanism  is  enfeebled  may  favour  thrombosis.  For 
anything  which  cripples  the  circulation,  and  consequently  limits  the 
free  interchange  between  blood  and  tissues,  interferes  with  the  elimina- 
tion or  neutralization  of  the  precursors  of  thrombin,  and  with  the 
entrance  of  the  substances  that  render  the  fully  formed  thrombin  in- 
active. This,  as  well  as  the  injury  caused  by  the  ligature,  which  may 
favour  the  passage  of  thromboplastic  substances  into  the  lumen  of  tlie 
occluded  vessel,  is  a  possible  factor  in  the  formation  of  the  clot 
on  which  the  surgeon  relies  for  the  permanent  sealing  of  ligated 
vessels. 

In  haemophilia,  a  disease  in  which  the  coagulation  of  the  blood  is 
characteristically  slow,  and  in  which  even  slight  wounds  may  occasion 
severe  or  fatal  haemorrhage,  the  thrombogen  (protlirombin)  has  been 
found  deficient  in  amount,  and  the  injection  of  normal  serum  or  the 
transfusion  of  normal  blood  has  been  used  with  temporary  advantage 
in  the  treatment  of  the  condition.  In  certain  cases  of  purpura,  how- 
ever, where  haemorrhage  also  occurs  with  abnormal  ease,  no  variation 
from  the  normal  could  be  detected  in  the  content  of  either  antithrombin 
.  or  prothrombin  (Howell).  Some  have  supposed  that  in  such  conditions 
the  fault  is  an  unnatural  fragility  of  the  small  vessels  rtither  than  a 
deficiency  in  tlie  power  of  the  blood  to  clot,  but  of  this  also  no  actual 
evidence  has  been  adduced.  Another  factor  on  which  the  promptness 
and  completeness  of  the  sealing  of  wounded  vessels  may  depend  has  been 
recently  brought  into  notice,  namely — 

The  Vaso-Constrictor  Property  of  Shed  Blood. — It  has  been  shown 
that  when  blood  is  shed  and  no  precautions  are  taken  to  prevent 
clotting,  it  very  quickly  develops  the  power  ot  causing  marked 
constriction  of  bloodvessels.     This  can  be  demonstrated  by  allow 
ing  the  serum  to  act  on  rings  cut  from  arteries  (I'ractical  Exercises, 


46  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

p.  66),  or  by  perfusing  the  hind-legs  of  frogs  with  a  sahne  solu- 
tion containing  serum.  Plasma  derived  from  blood  in  which  the 
platelets  have  been  prevented  from  breaking  down,  and  which 
therefore  remains  unclotted,  has  no  such  effect,  or  a  much  slighter 


Fig.  7. — Sheep  Artery  Rings.  At  14  and  16  Ringer's  solution  was  replaced  by  citrate 
plasma  (two  different  specimens).  At  15  and  17  the  plasmas  were  replaced  by 
the  corresponding  sera.  At  18  and  19  the  sera  replaced  Ringer's  solution  directly. 
Time-trace,  half-minutes.     Tracings  reduced  to  J. 

effect.  But  when  the  platelets  are  separated  from  the  plasma 
and  then  decomposed,  the  resulting  extracts  of  platelets  are  rich 
in  vaso-constrictor  material.  In  the  sealing  of  wounded  vessels 
the  platelets  would  therefore  appear  to  play  a  double  role,  yielding 


Fig  8. — Frog  Perfusion  Experiment  with  Serum.  The  drops  of  liquid  flowing  through 
the  preparation  are  recorded.  At  11  citrate  plasma  was  injected;  at  13  the 
corresponding  citrate  serum.  The  tracing  is  to  be  read  from  left  to  right. 
Time  is  marked  in  half -minutes 

a  substance  which  causes  constriction  of  the  vessel  in  the  neigh- 
bourhood of  the  wound  while  a  plug  of  clot  is  being  formed,  thanks 
to  other  substances  liberated  from  the  platelets,  which  take  an 
essential  part  in  coagulation.     The  vaso-constriction  may  perhaps 


VASO  CONSTRICTOR  PROPERTY  OF  SHED  BLOOD 


47 


be  looked  upon  as  a  form  of  '  first  aid  '  to  diminish  the  hamor- 
rhage,  and  also  to  make  it  less  easy  for  the  beginning  clot  to  be 
washed  away.  It  is  obvious  that  the  two  processes  would  be 
mutually  advantageous  in  dealing  with  those  injuries  of  the  vascular 
system  on  the  prompt  repair  of  which  the  very  existence  of  the 


i 
II                                                                                                   -  1 

A   ^ 

'/\r 

TV/' 

■f  [                         .r- 

\i 

_A_  r 

*"                                                                          v^ 

Jc.c  Serum i^ derate 

/cc  P/asma 

/cc  Rasma 

ICi.  Serurr^ciiraieA 

Fig.  9. — Frog  Perfusion  E.xperiment  with  Serum.  Curves  showing  the  flow.  The 
number  of  drops  per  half-minute  is  laid  off  along  the  vertical  a.xis,  and  the  time 
(in  half-minutes)  along  the  horizontal  a.xis;  38  drops  correspond  to  i  cc. 

organism  at  all  times  depends,  and  it  is  not  without  interest  to 
find  that  special  formed  elements  in  the  blood,  the  platelets,  are 
pre-eminently  associated  with  both  processes. 


Section  III. — The  Chemical  Composition  of  Blood. 

The  serum  of  coagulated  blood  represents  the  plasma  minus 
fibrinogen;  the  clot  represents  the  corpuscles  plus  fibrin.     Thus: 

Plasma  -  Fibrin(ogcn)  =  Serum. 

Corpuscles  +  Fibrin  =  Clot. 

Plasma  +  Corpuscles  =  Serum  +Clot  =  Blood. 

Bulky  as  the  clot  is,  the  quantity  of  fibrin  is  trifling  (0-2  to  0-4  per 
cent,  in  human  blood).  The  plasma  contains  about  10  per  cent, 
of  solids,  the  red  corpuscles  about  40  per  cent.,  the  entire  blood 
about  20  per  cent. 

Serum  contains  7  to  8  per  cent,  of  proteins,  about  o-8  per  cent, 
of  inorganic  salts,  and  small  quantities  of  neutral  fats,  soaps, 
cholesterin  esters,  lecithin,  dextrose,  urea,  lactic  acid,  glycuronic 

acid,  amino  -  acids, 

Sohds         VjaT^T  ^  ^  A  „4.i 

Corpuscles 
Flasntd 


and    other    sub- 
stanccs.      The  chief 
proteins  are   serum- 
albumin  and  serum- 
globulin.    In  the  rab- 
bit   the    former,    in 
the  horse  the  latter,  is  the  more  abundant ;  in  man  they  exist  in  not 
far  from  equal  amount.     A  small  quantity  of  nnclco-protein  and  of 
fibrino-globulin  (which  some  consider  a  sulubie  product  formed  from 


Fig.  10. — Diagram  showing  Relative  Quantity  of  Solids 
and  Water  in  Red  Corpuscles  and  Plasma. 


48  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

fibrinogen  in  clotting)  is  also  present.  Ferments  which  cause 
hydrolysis  of  proteins  and  carbohydrates,  a  ferment  (lipase)  which 
acts  upon  fats,  and  certain  oxidizing  femients  (oxydases),  have  also 
been  demonstrated.  The  chemical  nature  of  the  bodies  which 
confer  on  serum  or  plasma  its  specific  haemolytic,  agglutinating, 
precipitating,  and  bactericidal  properties  has  not  been  definitely 
determined. 

The  quantitative  composition  of  serum,  especially  as  regards  the 
inorganic  salts,  is  remarkably  constant  in  animals  of  the  same  species, 
and  even  in  animals  of  different  species  belonging  to  the  same,  or  to 
not  very  widelv  separated,  natural  groups.  In  cold-blooded  animals 
the  serum-albumin  is  scantier  than  in  mammals,  the  globulin  relatively 
more  plentiful. 

Serum-albumin  belongs  to  the  class  of  native  albumins.  It  has 
been  obtained  in  a  crj-stalline  form  from  the  serum  of  horse's  blood.     It 


Fig.  II. — Perspective  View  of  Vivi-Diffusion  Apparatus  (Abel).  This  form  of  the 
apparatus  contains  sixteen  tubes.  A.  arterial  cannula;  B,  venous  cannula; 
C.  side  tube  for  introduction  of  hirudin;  D,  inflow  tube;  E,  outlet  tube  for  the 
blood;  F,  G,  supporting  rod  attached  at  H  and  K  to  branched  V-tubes;  L,  burette 
for  hirudin;  M,  N,  tube  for  filling  and  emptying  liquid  in  outer  jacket;  O,  air 
outlet;  P,  dichotomous  branching-point  of  inflow  tube;  Q  and  R,  quadruple 
branching-points  of  the  same  ;  S,  S,  wooden  supports;  T,  thermometer.  At 
each  of  the  points  H  and  K  the  blood  is  collected  from  four  tub»s  into  one, 
bending  round  to  the  back,  and  there  redividing  into  four  return  flow  tubes. 
Arrows  show  the  direction  of  the  flow. 

is  soluble  in  distilled  water,  and  is  not  precipitated  by  saturating  its 
solutions  with  certain  neutral  salts.  Heated  in  neutral  or  slightly 
acid  solution,  it  coagulates  first  at  73°,  then  at  77°,  then  at  84°  C. 
Although  this  is  not  of  itself  sufficient  proof,  there  is  other  evidence 
that  it  consists  of  a  mixture  of  proteins. 

Serum-globulin,  also  called  paraglobulin,  belongs  to  the  globulin 
group  of  proteins.  When  heated,  it  coagulates  at  about  75°  C.  (p.  9). 
It  is  insoluble  in  distilled  water,  and  is  precipitated  by  saturation  with 
such  neutral  salts  as  magnesium  sulphate,  or  by  half-saturation  with 
ammonium  sulphate.  It  appears  that,  as  thus  obtained,  it  is  not  a 
single  substance,  but  a  mixture  of  at  least  two  proteins — eu-globulin, 


CHEMICAL  COMPOSITION  OF  BLOOD 


49 


which  can  be  precipitated  from  its  saline  solution  by  dialyzing  off  the 
salts,  and  pseudo-globulin,  which  cannot  be  so  precipitated. 

In  addition  to  the  nitrogen  represented  as  protein,  serum  (or  plasma) 
contains  non-protein  nitrogen,  the  amount  of  which  varies  with  the 
nature  of  the  food  and  the  stage  of  digestion.  Part  of  this  fraction  is 
attributable  to  urea  and  other  metabolites  on  their  way  to  be  excreted, 
but  another  portion,  and  an  important  one,  is  due  to  amino-acids 
absorbed  from  the  intestine  during  the  digestion  of  proteins  and  on 
their  way  to  be  utilized  in  the  tissues. 

Of  the  inorganic  salts  of  serum,  the  most  important  are  sodium 
chloride  and  sodium  bicarbonate.  Small  amounts  of  potassium, 
calcium,  and  magnesium,  united  with  phosphoric  acid  or  chlorine,  and 
a  trace  of  fluoride,  are  also  present.  A  portion  of  the  salts  is  loosely 
combined  with  the  proteins. 

Our  knowledge  of  the  chemistry  of  the  circulating  plasma  is  likely 
to  be  notably  augmented  by  the  method  of  vivi-diffusion  recently  intro- 
duced by  Abel.  An  artery  of  an  anaesthetized  animal  is  connected  by 
a  cannula  to  a  system  of  celloidin  tubes  immersed  in  a  saline  solution. 
Blood  passes  from  the  artery'  through  the  tubes,  where  it  exchanges 
diffusible  constituents  with  the  solution,  and  is  then  returned  to  the 
animal's  body  by  another  cannula  attached  to  a  vein.  Coagulation 
of  the  blood  in  the  apparatus  is  prevented  by  hirudin,  and  under 
aseptic  conditions  the  circulation  may  proceed  through  the  tubes  for  a 
long  time.  The  saline  solution  can  then  be  analyzed  for  substances  which 
have  entered  it  from  the  blood — amino-acids,  for  example  (Fig.  ii). 

The  following  tables  give  some  details  of  the  composition  of  blood : 


i,ooo  Grammes  of  Pig's  Blood  (Corpuscles,  435'09;  Serum,  564  91) 

CONTAINED 


Corpuscles. 

Serum. 

Corpuscles. 

Serum. 

Water 

272-20 

518-36 

P2O5  as  nuclein 

0-0455 

0-0123 

Solids 

i6i-89 

46-54 

Na.,0 

* 

2-401 

Haemoglobin 

142-20 

K.,0 

2-157 

0-152 

Protein 

8-35 

38-26 

Fe.,03 

0-696 



Sugar 

0-684 

CaO 



o-o68g 

Cholesterin 

0-213 

0-231    ' 

MgO 

0-0656 

0-0233 

Lecithin 

1-504 

0-805 

CI 

0-642 

2-048 

Fat  . . 

I-IO4 

P2O5 

0-895 

O-III 

Fatty  acids 

0-027 

0-448 

Inorga 

lie  P265 

0-719 

0--96 

Proteins  of  Plasma  in  1,000  Grammes. 


Albumin. 

Globulin. 

Fibrinogen. 

Tot«l. 

Man 

40-1 

28-3 

4-2 

72-6 

Dog 

3T-7 

22-6 

6-0 

60-3 

Sheep 

38-3 

30-0 

4-6 

72-9 

Horse 

28-0 

47-9 

4-5 

80-4 

Pig 

44-2 

29-8 

6-5 

80-5 

*  The  pig'.s  erythrocytes  are  peculiar   in  that  the  sodium  appears  to  be 
entirely  confined  to  the  plasma. 

4 


5<»  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

The  Coloured  Corpuscles  consist  of  rather  less  than  60  per  cent,  of 
water  and  rather  more  than  40  per  cent,  of  solids.  Of  the  solids  the 
pigment  haemoglobin  makes  up  about  90  per  cent. ;  the  proteins  and 
nucleo-protein  of  the  stroma  about  7  percent.;  lecithin  and  choles- 
terin  2  to  3  per  cent.;  inorganic  salts  (which  vary  greatly  in  their 
relative  proportions  in  different  animals,  but  in  man  consist  chiefly 
of  phosphates  and  chloride  of  potassium,  with  a  much  smaller 
amount  of  sodium  chloride)  about  i  per  cent.  Potassium  has  been 
demonstrated  microchemically  in  frog's  erythroc5;i;es  (Macallum) 
{Frontispiece) .  There  is  evidence  that  a  portion  of  the  salts  is  more 
firmly  combined  than  the  rest,  so  that,  even  after  the  action  of  the 
most  energetic  laking  agents,  this  fraction  remains  attached  to  the 
stroma.  The  erythrocytes  of  some  animals — e.g.,  the  dog — contain 
dextrose.  When  dextrose  is  added  to  human  blood  it  rapidly  dis- 
tributes itself  over  corpuscles  and  plasma  (Rona),  although  not 
exactly  in  proportion  to  their  respective  volumes  (Masing).  Hither- 
to the  dextrose  in  blood  has  been  reckoned  as  if  it  all  belonged  to  the 
plasma. 

Hcemoglobin. — Of  all  the  solid  constituents  of  the  blood,  haemoglobin 
is  present  in  greatest  amount,  constituting  as  it  does  no  less  than 
13  per  cent.,  by  weight,  of  that  liquid.     It  is  an  exceedingly  complex 

body,  containing  car- 
bon, hydrogen,  nitro- 
^A      gen,     and    oxygen    in 
ra.uch    the    same  pro- 
portions in  which  they 
exist  in  ordinary  pro- 
teins (p.  i).      Iron  is 
also  present  to  the  ex- 
tent of  almost  exactly 
Fig.  12.— Diagram  of  Spectroscope.     A,  source  of  light;     one-thirdof  I  percent., 
B,  layer  of  blood;   C,   collimator  for  rendering  rays     and  there  is  also  a  little 
parallel;  D,  prism;  E.  telescope.  sulphur,  the  amount  of 

which  stands  in  a  very 
simple  relation  to  the  quantity  of  iron  (i  atom  of  iron  to  3  of  sulphur 
in  dog's  haemoglobin,  and  i  atom  of  iron  to  2  of  sulphur  in  the  haemo- 
globin of  the  horse,  ox,  and  pig).  Haemoglobin  is  made  up  of  a  protein 
element  which  contains  all  the  sulphur  and  a  pigment  which  contains  all 
the  iron,  the  protein  constituting  by  far  the  larger  portion  of  the  gigantic 
molecule,  whose  weight  has  been  estimated  at  more  than  16,000  times 
that  of  a  molecule  of  hydrogen.  Since  its  percentage  composition  is 
still  undetermined  with  absolute  precision,  it  is  impossible  to  give  an 
empirical  formula  that  is  more  than  approximately  correct.  For  dog's 
heemoglobin  Jaquct  gives  C758Hi203Ni95S3FeO2i8.  which  would  make 
the  molecular  weight  16,669.  Direct  determinations  of  the  molecular 
weight  gave  15,115  for  oxyhaemoglobin  of  the  horse,  and  16,321  for  that 
of  the  ox  (Hiifner  and  Gansser).  While  these  numbers  need  not  be 
taken  as  more  than  a  rough  approximation,  they  at  least  show  that 
the  haemoglobin  molecule  is  an  exceedingly  large  one. 

The  most  remarkable  property  of  haemoglobin  is  its  power  of 
combining  loosely  with  oxygen  when  exposed  to  an  atmosphere  con- 


CHEMICAL  COMPOSITION  OF  BLOOD 


tt 


D  E  b  F 

6W  630  620  610  600  S^fi  580  570  560  550  bkO  J.1(i  51If\  510   500  190  m 

I        I         I        I    .    I    .    il       I     .    I    .    I     .    I     .    I         I        !  '      I     .    I     .    I    ,    I 


Fig.  13. — Table  of  Spectra  of  Haemoglobin  and  its  Derivatives  (Ziemka  and  Miiler). 
I ,  Oxyhitmoglobin ;  2, reduced  harnoglobin  3, methasmoglobin ;  4.  ac.d  ha;matin ; 
5.  alkaline  hsniatin;  6,  hamochromogen ;  7,  acid  ha?raatoporphyrin ;  8,  alkaline 
haematoporphyrin ;  9,  carbon  monoxide  ha;moglobia. 


52 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


taining  it,  and  of  again  giving  it  up  in  the  presence  of  oxidizable 
substances  or  in  an  atmosphere  in  which  the  partial  pressure  of 
oxygen  (pp.  250-253)  has  been  reduced  below  a  certain  limit.  It 
is  this  property  that  enables  haemoglobin  to  perform  the  part  of  an 
oxygen-carrier  to  the  tissues,  a  function  of  the  first  importance, 
which  will  be  more  minutely  considered  when  we  come  to  deal  with 
respiration. 

The  bright  red  colour  of  blood  drawn  from  an  artery  or  of  venous 
blood  after  free  exposure  to  air  is  due  to  the  fact  that  the  haemo- 
globin is  in  the  oxidized  state 
— in  the  state  of  oxyhaemo- 
globin,  as  it  is  called.  If  the 
oxygen  is  removed  by  means 
of  reducing  agents,  such  as 
ammonium  sulphide,  or  by  ex- 
posure to  the  vacuum  of  an 
air-pump,  the  colour  darkens, 
the  blood-pigment  being  now 
in  the  form  of  reduced  haemo- 
globin. In  ordinary  venous 
blood  a  large  proportion  of  the 
pigment  is  in  this  condition, 
but  there  is  always  oxyhaemo- 
globin  present  as  well.  In 
asphyxia  (p.  276),  however, 
nearly  the  whole  of  the  oxy- 
haemoglobin  may  disappear. 

Crystallization  of  Hamoglobin. 
— In  the  circulating  blood  the 
haemoglobin  is  related  in  such  a 
way  to  the  stroma  of  the  cor- 
puscles that,  although  the  latter 
are  suspended  in  a  liquid  readily 
capable  of  dissolving  the  pig- 
ment, it  yet  remains  under 
ordinary  circumstances  strictly 
within  them.  In  a  few  inver- 
tebrates, however,  it  is  nor- 
mally in  solution  in  the  cir- 
culating liquid.  As  a  rare  occurrence  haemoglobin  may  form  crystals 
inside  the  corpuscles  (p.  71).  When  it  is  in  any  way  brought  into  solu- 
tion outside  the  body,  it  shows  in  many  animals,  but  not  in  the  same 
degree  in  all,  a  tendency  to  crystallization  ;  and  the  ease  with  which 
crystallization  can  be  induced  is  in  inverse  proportion  to  the  solubility 
of  the  haemoglobin.  Thus,  it  is  far  more  difficult  to  obtain  crystals  of 
haemoglobin  from  human  blood  than  from  the  blood  of  the  rat,  guinea- 
pig,  or  dog,  whose  blood -pigment  is  less  soluble  than  that  of  man,  and 
for  a  like  reason  the  oxyhasmoglobin  of  the  bird,  the  rabbit,  or  the  frog 
crystallizes  still  less  readily  than  that  of  human  blood. 

As  to  the  form  of  the  crystals,  in  the  vast  majority  of  animals  they 


Fig.  14. — Oxyhasmoglobin  Crystals  (Frey). 
a,  b,  from  man ;  c,  from  cat ;  d,  from  guinea- 
pig;  e,  from  hamster;/,  from  squirrel. 


CHEMICAL  COMPOSITION  OF  BLOOD  53 

are  rhombic  prisms  or  needles,  but  in  the  guinea-pig  they  are  tetrahedra 
belonging  to  the  rhombic  system,  and  in  the  squirrel  six-sided  plates  of 
the  hexagonal  system  (Fig.  14).  Careful  study  of  the  crystallography  of 
haemoglobin  from  a  large  number  of  animals  has  established  differences 
and  resemblances  so  constant  and  so  clear-cut  that  they  may  be  used  for 
the  purposes  of  classification  and  for  the  identification  of  the  source  of 
a  specimen  of  blood  (Reichert  and  Brown). 

Reduced  haemoglobin  can  also  be  caused  to  crystallize,  though  with 
more  difficulty  than  oxyhc'emoglobin,  since  it  is  more  soluble.  Cr^'stals 
of  reduced  haemoglobin  were  first  prepared  from  human  blood  by  Hiifner, 
who  allowed  it  to  putrefy  in  sealed  tubes  for  several  weeks. 

When  a  solution  of  oxyhaemoglobin  of  moderate  strength  is  ex- 
amined with  the  spectroscope,  two  well-marked  absorption  bands 
are  seen,  one  a  little  to  the  right  of  Fraunhofer's  hne  D,  and  the  other 
a  Httle  to  the  left  of  E.  A  third  band  exists  in  the  extreme  violet 
between  G  and  H.  It  cannot  be  detected  with  an  ordinary  spectro- 
scope, but  has  been  studied  by  the  aid  of  a  fluorescent  eyepiece,  by 
projecting  the  spectrum  on  a  fluorescent  screen,  and  by  photograph- 
ing the  spectrum.  The  addition  of  a  reducing  agent,  such  as 
ammonium  sulphide,  causes  the  bands  in  the  visible  spectrum  to 
disappear,  and  they  are  replaced  by  a  less  sharply  defined  band,  of 
which  the  centre  is  about  equidistant  from  D  and  E.  This  is  the 
characteristic  band  of  reduced  haemoglobin.  The  spectrum  of 
ordinary  venous  blood  shows  the  bands  of  oxyhaemoglobin. 

Carbonic  oxide  hcBmoglobin  is  a  representative  of  a  class  of  hemo- 
globin compounds  analogous  to  oxyhaemoglobin,  in  which  the  loosely- 
combined  ox;^'gen  has  been  replaced  by  other  gases  (carbon  monoxide, 
nitric  oxide)  in  firmer  union.  Its  spectrum  shows  two  bands  very  like 
those  of  oxyhaemoglobin,  but  a  little  nearer  the  violet  end.  Carbonic 
oxide  haemoglobin  is  formed  in  poisoning  with  coal-gas.  Owing  to  the 
great  stability  of  the  compound,  the  haemoglobin  can  no  longer  be 
oxidized  in  the  lungs,  and  death  may  take  place  from  asphyxia.  It 
is,  however,  gradually  broken  up,  and  therefore  artificial  respiration 
may  be  of  use  in  such  cases.  Inhalation  of  ox>'gen  and  especially 
transfusion  of  blood  are  also  of  great  value. 

Methcpmoglobin  is  a  derivative  of  oxyhaemoglobin  which  can  be 
formed  from  it  in  various  ways,  e.g.,  by  the  addition  of  ferricyanide  of 
potassium  or  nitrite  of  amyl  (Gamgee),  by  electrolysis  (in  the  neigli- 
bourhood  of  the  anode),  or  by  the  action  of  the  oxidizing  ferment 
'  echidnase  '  in  the  poison  of  the  viper  (Phisalix).  It  very  often  appears 
in  an  oxyhaemoglobin  solution  which  is  exposed  to  the  air.  It  has  been 
found  in  the  urine  in  cases  of  haemoglobinuria,  in  the  fluid  of  ovarian 
cysts,  and  in  haematoceles.  The  strongest  band  in  its  spectrum  is 
in  the  red,  between  C  and  D,  but  nearer  C,  nearly  in  the  same  position 
as  the  band  of  acid-ha-matin.  Reducing  agents,  such  as  ammonium 
sulphide,  change  methamoglobin  first  into  ox>-haemoglobin  and  then 
into  reduced  haemoglobin.  It  has  by  some  been  regarded  as  a  more 
highly  oxidized  haemoglobin  than  ox^-hacmoglobin .  Rebutting  evidence 
has,  however,  been  offered  to  the  effect  that  the  same  quantit\-  of 
oxygen  is  required  to  saturate  both  pigments,  and  this  evidence  appears 
to  be  sound.  The  diftercnce  lies  ratlier  in  the  manner  in  which  the 
oxygen  is  united  to  the  ha-moglobin  in  tiic  mctluiMnoglobin  molecule 
than  in  the  quantity  of  oxygen  which  it  contains.     For   methanno- 


54 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


globin,  unlike  oxyha2moglobin,  parts  with  no  oxygen  to  the  vacuum, 
while,  on  the  other  hand,  in  the  presence  of  reducing  agents  it  yields  up 
its  oxygen  even  more  readily  than  oxyhaemoglobin  does  (Haldane) 
(p.  249). 

By  the  action  of  acids  or  alkalies  oxyhaemoglobin  is  split  into  a  pig- 
ment, haematin,  and  a  protein,  globin,  belonging  to  the  histon  group. 
It  is  easily  precipitated  from  solution  by  ammonia.  On  hydrolysis,  it 
yields  a  large  amount  of  histidin.to  which  its  basic  properties  are  chiefly 


^  - 


;R^ 


V. 


'^. 


(It^^ 

D 

E 

~     1 

1 

■    1    ;i 

1;   1 

—    1: 

;    1 

.1/0 

bandi 


ClxtjHh  1 

Carbonic  OAitieHh 
Haemoch  fc  moqe  '<  I 

Haetnatojiorfih  t/rtn  faciei}] 
Methaemo^/obin-         \ 
field  Haematin        '    I   '^/*«^ 
Alkali  n  e  Haemal  n't    f  T'^^ 
Reduced  Hb  l^"*"^ 


'^... 


D 


Fig.  15. — Diagram  to  sliow  the  Chief  Characteristics  by  which  Haemoglobin  and 
some  of  its  Derivatives  may  be  recognized  Spectroscopically.  The  position  of 
the  middle  of  each  band  is  indicated  roughly  by  a  vertical  line. 

due.  From  100  grammes  of  oxyhaemoglobin  about  4  grammes  of  hae- 
matin are  obtained.  As  to  the  pigment  moiety,  when  haemoglobin  is 
acted  on  by  acids  in  the  absence  of  oxygen,  hceniochromogen  is  first 
formed,  which  then  gradually  loses  its  iron  and  is  changed  into  haemato- 
porphyrin.  If  oxygen  be  present,  haematin  is  the  final  product. 
Haematin  may  be  considered  as  the  compound  which  haemochromogen 
forms  with  oxygen.  By  the  action  of  alkalies  reduced  haemoglobin 
yields  haemochromogen,  which  is  stable  in  alkaline  solution,  and  gives 

a  beautiful  spectrum 


X/v«r  zg-5 

TTuicks  t9'2 

Qr«iiT  ./cMelSiheart*  ^vngs   22*7 
Bones  82 

hliel'^nesv  aenitiil  organs  6-3 
^AiD  21 

Kidneys  f6 

"Nerve  centres    i'2 
Sp]eea  "^ 


with  two  bands, 
bearing  some  resem- 
blance to  those  of 
oxyhaemoglobin,  but 
placed  nearer  the 
violet  end.  The  band 
next  the  red   end   is 


Fig.  16.— Diagram  to  illustrate  the  Distribution  of  the  much  sharper  than 
Blood  in  the  Various  Organs  of  a  Rabbit  (after  Ranke's  the  other  (p.  76). 
Measurements).  The  numbers  are  percentages  of  the  Haemochromogen 
total  blood.  binds  exactly  the 

same  amount  of  oxy- 
gen as  the  haemoglobin  from  which  it  is  derived,  and  it  is  due  to  the 
haemochromogen  in  its  molecule  that  the  bood  -  pigment  fulfils  its 
function  of  taking  up  and  transporting  oxygen. 

HcBwiatin  (C32H3204N4.FeOH),  the  most  frequent  result  of  the 
splitting  up  of  haemoglobin,  is  generally  obtained  as  an  amorphous 
substance  with  a  bluish-black  colour  and  a  metallic  lustre,  insoluble 
in  water,  but  soluble  in  dilute  alkalies  and  acids,  or  in  alcohol  containing 
them.  In  addition  to  the  iron  of  the  haemoglobin,  haematin  contains 
the  four  chief  elements  of  proteins — carbon,  hydrogen,  nitrogen,  and 
oxygen  (Practical  Exercises,  p.  75). 


QUANTITY  AND  DISTRIBUTION  OF  BLOOD  55 

Hcsmato porphyrin  (C^^H^QOaSi),  or  iron-free  haematin,  may  be 
obtained  from  blood  or  haemoglobin  by  the  action  of  strong  sulphuric - 
acid,  from  haematin  or  haemin  by  the  action  of  hydrobromic  acid.  It 
is  distinguished  from  these  pigments  by  the  fact  that  it  contains  no 
iron.  When  strong  sulphuric  acid  is  allowed  to  act  on  blood  or  haemo- 
globin solution,  haematoporphyrin  is  also  produced,  as  may  be  easily 
shown  by  the  spectroscope.  Its  spectrum  in  acid  solution  shows  two 
bands,  one  just  to  the  left  of  D,  the  other  about  midway  between  D 
and  E.  Like  oxyhaemoglobin,  reduced  haemoglobin,  carbonic  oxide 
haemoglobin,  methaemoglobin,  and  other  derivatives  of  haemoglobin, 
it  also  has  a  band  in  the  ultra-violet. 

Ht^min  (C3.2H..5204N4.FeCl)  is  readily  obtained  from  haematin  and 
also  from  haemoglob  n  by  heating  witli  dilute  hydrochloric  acid,  and  also 
directly  from  blood,  as  described  in  the  Practical  Exercises,  p.  78.  It 
crystallizes  in  the  form  of  small  rhombic  plates,  of  a  brownish  or 
brownish-black  colour  (Fig.  2^,  p.  78).  They  are  insoluble  in  water, 
but  readily  soluble  in  dilute  alkalies  (Practical  Exercises,  p.  79). 

Chemistry  of  the  White  Blood- Corpuscles. — -The  composition  of  pus- 
cells  and  the  leucocytes  of  lymphatic  glands  has  alone  been  investigated. 
The  chief  constituents  of  the  latter  are  a  globulin  coagulating  by  heat 
at  48°  to  50°  C. ;  a  nucleo-protein  coagulating  in  5  per  cent,  magnesium 
sulphate  solution  at  75°  C.,  and  causing  coagulation  of  the  blood  on 
injection  into  the  veins  of  rabbits;  an  albumin  coagulating  at  73°  C. ; 
and  a  ferment  with  powers  like  the  pepsin  of  the  gastric  juice.  In  pus- 
cells  gh'cogen  has  been  found,  and  it  can  be  demonstrated  micro- 
chemically  in  the  leucocytes  of  blood  by  the  iodine  reaction  in  various 
conditions.  Fats,  cholesterin,  and  lecithin  are  also  present,  as  well 
as  the  so-called  protagon.  The  ordinary^  inorganic  constituents  have 
been  demonstrated — ^namely,  potassium,  sodium,  calcium,  magnesium, 
and  iron,  united  with  chlorine  and  phosphoric  acid.  The  total  solids 
amount  to  11  to  12  per  cent. 

Section  IV. — Quantity  and  Distribution  of  the  Blood. 

The  Quantity  of  Blood. — The  quantity  of  blood  in  an  animal  is 
most  accurately  determined  by  the  method  of  Welcker.  The  animal 
is  bled  from  the  carotid  into  a  weighed  flask.  When  blood  has 
ceased  to  flow  the  vessels  are  washed  out  with  water  or  physiological 
saline  solution,  and  the  last  traces  of  blood  are  removed  by  chopping 
up  the  body,  after  the  intestinal  contents  have  been  cleared  away, 
and  extracting  it  with  water.  The  extract  and  washings  are  mixed 
and  weighed;  a  given  quantity  of  the  mixture  is  placed  in  a  haema- 
tinometer  (a  glass  trough  with  parallel  sides,  e.g.),  and  a  weighed 
quantity  of  the  unmixed  blood  diluted  in  a  similar  vessel  till  the  fint 
is  the  same  in  both.  From  the  amount  of  dilution  required,  the 
quantity  of  blood  in  the  watery  solution  can  be  calculated.  This  is 
added  to  the  amount  of  unmi.xed  blood  directly  determined.  Since 
haemorrhage  is  immediately  followed  by  the  entrance  of  liquid  into 
the  bloodvessels  from  the  lymph  and  tissue  fluids,  somewhat  too 
high  a  result  will  be  obtained  if  the  bleeding  is  at  all  prolonged.  It 
is  well,  therefore,  to  take  only  a  moderate  amount  of  blood  for  direct 
estimation,  and  to  compute  the  balance  by  the  colorimetric  method. 


56  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

Many  other  methods  have  been  devised  on  the  principle  of  in- 
jecting a  known  quantity  of  some  substance  into  the  circulating 
blood,  and  then,  after  an  interval  has  been  allowed  for  mixture, 
determining  the  change  produced  in  a  sample.  Thus,  the  specific 
gravity  of  a  drop  of  blood  having  been  measured,  a  certain  quantity 
of  a  solution  of  sodium  chloride  isotonic  ^^dth  the  plasma  may  be 
injected  into  a  vein,  and  the  specific  gravity  again  determined.  Or 
the  electrical  resistance  of  a  small  sample  of  blood  may  be  measured 
before  and  after  injection  of  a  given  quantity  of  isotonic  salt  solution. 

The  quantity  of  blood  in  the  body  was  greatly  overestimated  by 
the  ancient  physicians.  Avicenna  put  it  at  25  lb.,  and  many  loose 
statements  are  on  record  of  as  much  as  20  lb.  being  lost  by  a  patient 
without  causing  death.  By  Welcker's  method  the  proportion  of 
blood  to  body- weight  has  been  found  to  be  in  the  dog  i  :  13,  cat  i  :  14, 
horse  i  :  15,  frog  i  :  17,  rabbit  i  :  19,  fowl  i  :  20.  In  new-bom 
children  the  proportion  was  i  :  19,  in  adult  human  beings  (executed 
criminals)  i  :  13.  The  total  mass  of  the  blood  in  a  living  man  has 
been  estimated  by  causing  the  person  to  inhale  a  known  volume  of 
carbon  monoxide  mixed  with  oxygen  or  air,  and  then  determining 
in  a  sample  of  blood  taken  from  the  finger  the  percentage  amount  to 
which  the  haemoglobin  has  become  saturated  with  carbon  monoxide. 
All  that  remains  is  to  estimate  the  volume  of  carbon  monoxide  (or, 
what  is  precisely  the  same  thing,  the  volume  of  oxygen)  which 
100  cc.  of  blood  \n\\  take  up.  This  latter  quantity  is  called  the 
percentage  oxygen  capacity.  From  these  data  the  total  volume  of 
the  blood  can  be  calculated.  If  the  volume  is  multiplied  by  the 
specific  gravity  the  mass  is  obtained. 

Thus,  if  the  haemoglobin  was  found  to  be  25  per  cent,  saturated  with 
carbon  monoxide  after  the  person  had  absorbed  150  cc.  of  that  gas, 
the  whole  of  the  blood  would  require  600  cc.  of  carbon  monoxide  to 
saturate  it  completely.  If  the  percentage  oxygen  capacity  was  20, 
20  cc  of  OKy'gen  or  carbon  monoxide  would  be  needed  to  saturate 
100  cc  of  blood.     Therefore  the  total  volume  of  the  blood  would  be 

600  X  —  =  3,000  cc.     And  the  mass,  if  the  specific  gravity  was  i*055, 

would  be  3,000  X  I '055  =  3, 165  grammes.  According  to  this  method 
the  blood  on  the  average  in  man  constitutes  only  4-9  per  cent.,  or 
■A-r,  of  the  body-weight  (say,  ^\  kilogrammes  in  a  70  kilo  man),  var^ung 
in  fourteen  persons  between  y'g  and  ^^,,.  There  is  reason,  however,  for 
thinking  that  the  method — at  least,  as  hitherto  employed — underesti- 
mates the  quantity  of  blood.  According  to  Dreyer,  the  blood  volume 
is  a  function  of  the  surface  of  the  body,  so  that  the  smaller  and  lighter 
animals  in  any  given  species  have  a  relatively  greater  blood  volume 
than  the  larger  and  heavier  individuals.  Accordingly,  he  considers 
tliat  the  practice  of  expressing  the  volume  of  blood  as  a  percentage  of 
tiie  body-weight  should  be  abandoned. 

Fig.  16  (p.  54)  illustrates  the  distribution  of  the  blood  in  the 
various  organs  of  a  rabbit.  The  liver  and  skeletal  muscles  each  con- 
tain rather  more  than  one-fourth;  the  heart,  lungs,  and  great  vessels 


LYMPH  AND  CHYLE  57 

rather  less  than  one- fourth ;  and  the  rest  of  the  body  about  one-fifth, 
of  the  total  blood.  The  kidney  and  spleen  of  the  rabbit  each  contain 
one-eighth  of  their  ovvn  weight  of  blood,  the  liver  between  one-third 
and  one-fourth  of  its  weight,  the  muscles  only  one-twentieth  of  their 
weight. 

Section  V. — Lymph  and  Chyle. 

Lymph  has  been  defined  as  blood  without  its  red  corpuscles 
(Johannes  j\Iiiller) ;  it  resembles,  in  fact,  a  dilute  blood-plasma, 
containing  leucocytes,  some  of  which  (lymphocytes)  are  common  to 
lymph  and  blood,  others  (coarsely  granular  basophile  cells,  present 
only  in  small  numbers)  are  absent  from  the  blood.  L>Tnph  also 
contains  thrombocytes.  The  reason  of  this  similarity  appears  when 
it  is  recognized  that  the  plasma  of  tissue-lymph  (p.  460)  is  derived, 
in  large  part  at  any  rate,  from  the  plasma  of  blood  by  a  process  of 
physiological  filtration  (or  secretion)  through  the  walls  of  the 
capillaries  into  the  lymph-spaces  that  everywhere  occupy  the  inter- 
stices of  areolar  tissue,  while  the  l^nnph  of  the  lymphatic  vessels  is 
in  turn  derived  from  the  tissue  fluid.  But  in  addition  to  the  con- 
stituents of  the  plasma,  lymph  contains  substances  produced  in  the 
metabolism  of  the  tissues  which  pass  into  it  directly.  As  collected 
from  one  of  the  large  lymphatic  vessels  of  the  limbs,  or  from  the 
thoracic  duct  of  a  fasting  animal,  lymph  is  a  colourless  or  some- 
times yello\vish  or  slightly  reddish  liquid  of  alkaline  reaction.  Its 
specific  gravity  is  much  less  than  that  of  the  blood  (1015  to  1030). 
It  coagulates  spontaneously,  but  the  clot  is  always  less  firm  and  less 
bulky  than  that  of  blood.  The  plasma  contains  fibrinogen,  from 
which  the  fibrin  of  the  clot  is  derived.  Serum-albimiin  and  serum- 
globulin  are  present  in  much  the  same  relative  proportion  as  in  blood, 
although  in  smaller  absolute  amount.  Neutral  fats,  urea,  and  sugar 
are  also  found  in  small  quantities.  The  inorganic  salts  are  the  same 
as  those  of  the  blood-serum,  and  exist  in  about  the  same  amount, 
sodium  preponderating  among  the  bases,  as  it  does  in  serum.  The 
following  table  shows  the  results  of  analyses  of  lymph  from  man  and 
the  horse  (Munk) : 


Water 

I  Fibrin 
Other  proteins 
Solids  -  Fat     - 

Extractives* 
i  Salts    - 


Man. 


95-0  per  cent, 
o-i      I 


trace 
0-5 


Horse. 


95 "8  per  cent, 
o-i      ^ 

2-9 

trace  )  4-2 


O-I    ^ 

2-9 

trace  "■ 

O-I 

i-i     ) 


*  The  term  '  extractives  '  is  somewhat  loosely  applied  to  organic  substances 
which  exist  in  so  small  an  amount,  or  have  such  indefinite  chemical  characters, 
that  they  cannot  be  separately  estimated,  and  are  extracted  together  from  the 
residue  by  various  solvents. 


58 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


Chyle  is  merely  the  name  given  to  the  lymph  coming  from  the 
alimentary  canal.  The  fat  of  the  food  is  absorbed  by  the  lym- 
phatics, and  during  digestion  the  chyle  is  crowded  with  fine  fatty 
globules,  which  give  it  a  milky  appearance.  There  may  also  be  in 
chyle  a  few  red  blood-corpuscles,  carried  into  the  thoracic  duct  by  a 
back-flow  from  the  veins  into  which  it  opens.  Chyle  clots  like 
ordinary  U^mph,  the  size  of  the  clot  varying  according  to  the  quantity 
of  fat  present  and  enmeshed  by  the  fibrin.  Wounds  of  the  thoracic 
duct  or  of  lymphatics  opening  into  it  are  occasionally  produced  in 
operations  on  the  neck,  and  when  these  remain  open  ch3de  may  be 
readily  collected.  In  samples  obtained  from  a  patient  only  a  week 
after  the  section  of  a  branch  of  the  duct  during  an  operation  for  the 
removal  of  tubercular  glands,  water  constituted  928-90  parts  in 
1,000,  total  solids  71-10,  inorganic  solids  6-04,  organic  solids  65-06, 
proteins  18-52,  ether  extract  (fatty  substances)  19-30  (Sollmann). 
The  following  is  the  composition  of  a  sample  analyzed  by  Paton,  and 
obtained  from  a  fistula  of  the  thoracic  duct  in  a  man: 


Water 
Solids 

Inorganic  - 
Organic     - 

Proteins 

Fats 

Cholesterin 

Lecithin 


953-4 
46-6 

6-5 
40-1 

137 
24-06 
0-6 
0-36 


The  quantity  of  chyle  flowing  from  the  fistula  was  estimated  at  as 
much  as  3  to  4  kilos  per  twenty-four  hours,  or  nearly  as  much  as  the 
whole  of  the  blood.  The  flow  has  been  calculated  in  various  animals 
at  one-eighteenth  to  one-seventh  of  the  body-weight  in  the  twenty- 
four  hours.  The  quantity  of  lymph  in  the  body  is  unknown,  but  it 
must  be  very  great — perhaps  two  or  three  times  that  of  the  blood. 

Allied  to  tissue-lymph,  but  not  identical  with  it,  are  the  fluids 
present  in  health  in  very  small  amount  in  such  serous  cavities  as  the 
pericardium.  The  synovial  fluid  of  the  joints  differs  from  lymph 
especially  in  containing  a  small  amount  of  a  mucin-like  substance.. 

The  aqueous  humour,  and  still  more  the  cerebro-spinal  fluid,  are 
characterized  by  a  marked  deficiency  in  solids,  especially  protein. 
In  the  following  table  (from  Spifo)  the  differences  in  the  composition 
of  lymph  and  allied  fluids  from  differtnt  parts  of  the  body  are  illus- 
trated. 


Water  - 
Salts  - 
Fat  - 
Protein 


Man  :  Lymph  from 
Fistula  in  Thigh. 


96-4    to  94-3 

0-7       ,,       0-87 
0-06    ,,       0-22 

4 


2-8 


} 


Horse :  lA'mph 

from  Neik  during 

Mastication. 


95 
075 


37 


Aqueous 
Humour. 


987 

0-5  to  o- 

0-72 


Cerebro-Spinal 
Fluid. 


99  to  99-2 

0-02  to  0-16 


FUNCTIONS  OF  BLOOD  AND  LYMPH  59 

The  gases  of  the  blood  and  lymph  will  be  treated  of  in 
Chapter  IV.,  the  formation  of  lymph  in  Chapter  VIII.,  its  circulation 
in  Chapter  III. 

Section  VI. — The  Functions  of  Blood  and  Tymph. 

We  have  already  said  that  these  hquids  provide  the  tissues  with 
the  materials  they  require,  and  carry  away  from  them  materials 
which  have  served  their  turn  and  are  done  wnth.  These  materials 
are  gaseous,  liquid,  and  solid.  Oxygen  is  brought  to  the  tissues  in 
the  red  corpuscles ;  carbon  dioxide  is  carried  away  from  them  partly 
in  the  erythrocytes,  but  chiefly  in  the  plasma  of  the  blood  and 
lymph.  The  water  and  sohds  which  the  cells  of  the  body  take  in 
and  give  out  are  also,  at  one  time  or  another,  constituents  of  the 
plasma.  The  heat  produced  in  the  tissues,  too,  is,  to  a  large  extent, 
conducted  into  the  blood  and  distributed  by  it  throughout  the  body. 
The  leucocytes,  as  will  be  seen  farther  on,  aid  in  some  measure  in  the 
absorption  of  certain  of  the  food  substances  from  the  intestine.  It  is 
not  known  whether,  apart  from  this,  they  play  any  role  in  the  normal 
nutrition  of  other  cells,  although  it  is  probable  that  they  exercise  an 
influence  on  the  plasma  in  which  they  live.  But  they  have  impor- 
tant functions  of  another  kind,  to  which  it  is  necessary  to  refer  briefly 
here.  ~ 

Phagocytosis. — Certain  of  the  amoeboid  cells  of  blood  and  lymph, 
and  the  cells  of  the  splenic  pulp,  are  able  to  include  or  '  eat  up  ' 
foreign  bodies  with  which  they  come  in  contact,  in  the  same  way  as 
the  amoeba  takes  in  its  food.  Such  cells  are  called  phagocytes;  and 
it  is  to  be  remarked  that  this  term  neither  comprises  all  leucocytes 
nor  excludes  all  other  cells,  for  some  fixed  cells,  such  as  those  of  the 
endothelial  lining  of  bloodvessels,  are  phagocytes  in  virtue  of  their 
power  of  sending  out  protoplasmic  processes,  while  the  small, 
relatively  immobile  lymphoc3^e  is  not  a  phagocyte. 

Although  it  is  not  at  present  possible  to  assign  a  physiological 
value  to  all  the  phenomena  of  phagocytosis,  either  as  regards  the 
phagocytes  themselves  or  as  regards  the  organism  of  which  they 
form  a  part,  there  seems  little  doubt  that  under  certain  circumstances 
the  process  is  connected  with  the  removal  of  structures  which  in  the 
course  of  -development  have  become  obsolete,  or  with  the  neutral- 
ization or  elimination  of  harmful  substances  introduced  from  with- 
out, or  formed  by  the  activity  of  bacteria  within  the  tissues.  During 
the  metamorphosis  of  some  larvae,  groups  of  cilia  and  muscle-fibres 
may  be  absorbed  and  eaten  up  by  the  leucocytes.  In  the  metamor- 
phosis of  maggots,  for  example,  the  muscular  fibres  of  the  abdominal 
wall,  which  are  used  in  creeping,  and  are  therefore  not  required  in 
the  adult,  degenerate,  and  are  devoured  by  swarms  of  leucocytes 
which  migrate  into  them.     In  the  human  subject  an  example  of 


6o  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

absorption  of  tissue  by  the  aid  of  leucocytes  is  the  removal  of  the 
necrosed  decidua  reflexa,  the  fold  of  uterine  mucous  membrane 
which  envelops  the  ovum  (Minot). 

The  behaviour  of  phagocytes  towards  pathogenic  micro-organisms 
is  of  even  greater  interest  and  importance.  Metchnikoff  laid  the 
foundation  of  our  knowledge  of  this  subject  by  his  researches  on 
Daphnia,  a  small  crustacean  with  transparent  tissues,  which  can  be 
observed  under  the  microscope.  When  this  creature  is  fed  with  a 
fungus,  Monospora,  the  spores  of  the  latter  find  their  way  into  the 
body-cax-ity.  Here  they  are  at  once  attacked  by  the  leucocytes, 
ingested,  and  destroyed.  But  after  a  time  so  many  spores  get 
through  that  the  leucocj^es  are  unable  to  deal  with  them  all ;  some 
of  them  develop  into  the  first  or  '  conidium  '  stage  of  the  fungus;  the 
conidia  poison  the  leucocytes,  instead  of  being  destroyed  by  them, 
and  the  animal  generally  dies.  Occasionally,  however,  the  leuco- 
cytes are  able  to  destroy  all  the  spores,  and  the  life  of  the  Daphnia  is 
preserved.  This  battle,  ending  sometimes  in  victory,  sometimes  in 
defeat,  is  believed  by  Metchnikoff  to  be  typical  of  the  struggle  which 
the  phagocytes  of  higher  animals  and  of  man  seem  to  engage  in 
when  the  germs  of  disease  are  introduced  into  the  organism.  He 
supposes  that  the  immunity  to  certain  diseases  possessed  naturally 
by  some  animals,  and  which  may  be  conferred  on  others  by  vaccina- 
tion with  various  protective  substances,  is,  to  a  large  extent,  due  to 
the  early  and  complete  success  of  the  phagocytes  in  the  fight  with 
the  bacteria;  and  that  in  rapidly- fatal  diseases — such  as  chicken- 
cholera  in  birds  and  rabbits,  and  anthrax  in  mice — the  absence  of 
any  effective  phagocytosis  is  the  factor  which  determines  the  result. 
Others  have  laid  stress  on  the  action  of  protective  substances  sup- 
posed to  exist  in  the  plasma  itself.  It  is  possible  that  such  sub- 
stances are  manufactured  by  the  leucocytes,  and  either  given  off  by 
them  to  the  plasma  by  a  process  of  '  excretion,'  or  liberated  by  their 
complete  solution. 

The  most  recent  investigations  go  to  show  that  Metchnikoff' s 
phagocytic  theory  of  immunity  requires  modification,  at  any  rate  in 
the  case  of  the  higher  animals  and  man,  although  the  brilliant 
biological  observations  on  which  it  was  originally  built  retain  all 
their  value.  He  supposed  that  in  the  immunizing  process  the 
leucocytes  underwent  certain  changes,  acquired,  so  to  speak,  a  sort 
of  '  education  '  that  enabled  them  to  cope  with  bacteria  against 
which  they  were  previously  powerless.  It  seems  more  probable 
that  in  the  presence  of  the  substances  that  confer  immunity,  not  only 
the  leucocytes,  but  other  cells,  are  stimulated  to  produce  bodies 
which  cut  short  the  life,  or  inhibit  the  growth,  of  the  bacteria 
(alexins),  or  prepare  them  for  being  taken  up  by  the  phagocytes 
(opsonins).  It  has  been  shown  that  bacteria  which  have  been  in 
contact  with  serum  containing  the  appropriate  opsonins  are  taken 


FUNCTIONS  OF  BLOOD  AND  LYMPH  6i 

up  readily  by  leucocytes  washed  free  from  serum  constituents  by 
physiological  salt  solution,  whereas  the  washed  leucocytes  either  do 
not  ingest  bacteria  which  have  not  been  acted  on  by  serum,  or  take 
them  up  in  much  smaller  numbers.  There  is  some  evidence  that  in 
certain  bacterial  infections — ^for  example,  chronic  furunculosis,  a 
condition  in  which  crops  of  boils  continue  to  appear — the  grip  of  the 
bacteria  on  the  body  is  perpetuated  by  a  deficiency  in  the  amount  or 
in  the  activity  of  opsonins  capable  of  acting  specifically  upon  the 
micro-organisms  in  question.  A  numerical  expression,  which  in 
certain  cases,  perhaps,  gives  a  measure  of  the  patient's  resistance  to 
the  infection,  has  been  worked  out  by  Wright  under  the  name 
'  opsonic  index.'  This  index  is  the  ratio  between  the  average 
number  of  bacteria  taken  up,  under  certain  fixed  conditions,  by  each 
polymorphonuclear  leucocyte  in  an  emulsion  made  with  the  patient's 
serum,  and  the  average  number  taken  up  by  similar  leucocytes  in  an 
emulsion  made  with  normal  serum.  The  significance  of  this  index 
and  even  the  practicabihty  of  the  methods  used  to  ascertain  it,  are 
still  the  subject  of  discussion. 

Diapedesis. — The  fact  that  leucoc5d:es  can  pass  out  of  the  blood- 
vessels into  the  tissues  has  a  very  important  bearing  on  the  subject 
of  phagocytosis.  The  phenomenon  is  called  diapedesis,  and  is  best 
seen  when  a  transparent  part,  such  as  the  mesentery  of  the  frog,  is 
irritated.  The  first  effect  of  irritation  is  an  increase  in  the  flow  of 
blood  through  the  affected  region.  If  the  irritation  continues,  or  if 
it  was  originally  severe,  the  current  soon  begins  to  slacken,  the 
corpuscles  stagnate  in  the  vessels,  and  inflammatory  stasis  is  pro- 
duced. The  leucocytes  adhere  in  large  numbers  to  the  walls  of  the 
capillaries,  and  particularly  of  the  small  veins,  and  then  begin  to  pass 
slowly  through  them  by  amoeboid  movements,  the  passage  taking 
place  at  the  junctions  between,  or  it  may  be  through  the  substance  of, 
the  endothelial  cells.  Plasma  is  also  poured  out  into  the  tissues, 
the  whole  forming  an  inflammatory  exudation.  Even  red  blood- 
corpuscles  may  pass  out  of  the  vessels  in  small  numbers.  The 
exudation  may  be  gradually  reabsorbed,  or  destruction  of  tissue 
may  ensue,  and  a  collection  of  pus  be  formed.  The  cells  of  pus  are 
emigrated  leucocj^es  (Practical  Exercises,  Chap.  IIL,  p.  191). 

Their  emigration  is  connected  with  the  defence  of  the  organism 
against  the  entrance  of  certain  forms  of  bacteria  at  the  seat  of 
injury,  and  with  the  repair  of  the  injured  tissue,  but  the  nature  of 
the  summons  which  gathers  them  there  is  not  yet  clearly  under- 
stood. It  is  probably  some  sort  of  chemical  attraction  (chemio- 
taxis)  between  constituents  of  the  bacteria  or  decomposition  prod- 
ucts of  the  injured  tissue  on  the  one  hand,  and  constituents  of  the 
leucocytes  on  the  other. 

As  for  the  blood-plates,  it  will  suffice  to  say  by  way  of  summary 
that  their  important  function  in  the  sealing  of  wounded  vessels  (p.  46) 


62  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

is  the  sole  office  which  at  present  can  be  attributed  to  them.  And 
if  it  is  permissible  to  consider  the  leucocytes  as  a  patrol  for  the 
defence  of  the  tissues  in  general  against  invading  micro-organisms,  it 
may  perhaps  not  be  too  far-fetched  an  idea  to  look  upon  the  blood- 
plates  as  essentially  a  patrol  in  the  interests  of  the  anatomical 
integrity  of  the  vascular  system  itself.  This  does  not  exclude  the 
possibihty  that  the  clotting  of  extravasated  plasma  may  furnish  a 
more  favourable  medium  for  the  processes  of  repair  in  all  injured 
tissues. 


PRACTICAL  EXERCISES  ON  CHAPTER  II, 

N.B. — In  the  following  exercises  all  experiments  on  animals  which 
would  cause  the  slightest  pain  are  to  be  done  under  complete  ancesthesia. 

1.  Reaction  of  Blood. — (i)  Put  a  drop  of  fresh  dog's  or  ox  blood  on 
a  piece  of  glazed  neutral  litmus  paper  (the  litmus  paper  can  be  glazed 
by  dipping  it  into  a  neutral  solution  of  gelatin  and  allowing  it  to  dry). 
Wash  the  blood  off  in  lo  to  30  seconds  with  distilled  water.  A  bluish 
stain  will  be  left,  showing  that  fresh  blood  is  alkaline.  (2)  Repeat  with 
dog's  or  ox  serum.  It  is  not  necessary  to  wash  the  serum  off,  as  it 
does  not  obscure  the  change  of  colour.  (3)  Repeat  (i)  with  human 
blood.  With  a  clean  suture-needle  or  a  good-sized  sewing-needle 
which  has  been  sterilized  in  the  flame  of  a  Bunsen  burner,  prick  one  of 
the  fingers  behind  the  nail.  Bandaging  the  finger  with  a  handkerchief 
from  above  downwards,  so  as  to  render  its  tip  congested,  will  often 
facilitate  the  getting  of  a  good-sized  drop,  but  for  quantitative  experi- 
ments, like  2,  10,  and  17  (4),  this  should  not  be  done. 

2.  Specific  Gravity  of  Blood — Hammerschlag's  Method. — (i)  Put  a 
mixture  of  chloroform  and  benzol  of  specific  gravity  i  •060  into  a  small 
glass  cylinder.  Put  a  drop  of  dog's  or  ox  defibrinated  blood  into  the 
mixture  by  means  of  a  small  pipette.  If  the  drop  sinks  add  chloroform, 
if  it  rises  add  benzol,  till  it  just  remains  suspended  when  the  liquid  has 
been  well  stirred.  Then  with  a  small  hydrometer  measure  the  specific 
gravity  of  the  mixture,  which  is  now  equal  to  that  of  the  blood.  Filter 
the  liquid  to  free  it  from  blood,  and  put  it  back  into  the  stock-bottle. 
(2)  Obtain  a  drop  of  human  blood  as  in  i,  and  repeat  the  measurement 
of  the  specific  gravit3\ 

3.  Coagulation  of  Blood.* — (i)  Take  three  tumblers  or  beakers,  label 
them  a,  l-i,  and  y.  and  measure  into  each  100  c.c.  of  water.  Mark  the 
level  of  the  water  by  strips  of  gummed  paper,  and  pour  it  out.  (If  a 
sufficient  number  of  graduated  cylinders  is  available,  they  may  of 
cour.se  be  used,  and  this  measurement  avoided.)  Into  a  put  25  c.c 
of  a  saturated  solution  of  magnesium  sulphate,  into  ^  25  c.c.  of  a  i  per 
cent,  solution  of  potassium  or  ammonium  oxalate  in  0-9  per  cent, 
solution  of  sodium  chloride,  and  into  y  25  c.c.  of  a  i'2  per  cent,  solution 
of  sodium  fluoride  in  c-g  per  cent,  salt  solution.  If  the  dog  provided 
is  a  large  one,  these  quantities  may  be  all  doubled ;  for  a  small  dog  they 
may  be  all  halved. 

*  This  experiment  requires  two  laboratory  periods,  the  various  blood  mix- 
tures being  obtained  during  the  first  and  worked  up  during  the  second. 


PRACTICAL  EXERCISES  53 

(2)  Insert  a  cannula  into  the  central  end  of  the  carotid  artery  of  a 
dog  anaesthetized  with  morphine*  and  ether,  or  A.C.E.  mixture. f 

To  put  a  Cannula  into  an  Artery. — Select  a  glass  cannula  of  suitable 
size,  feel  for  the  artery,  make  an  incision  in  its  course  through  the 
skin,  then  isolate  about  an  inch  of  it  with  forceps  or  a  blunt  needle, 
carefully  clearing  away  the  fascia  or  connective  tissue.  Next  pass  a 
small  pair  of  forceps  under  the  artery,  and  draw  two  ligatures 
through  below  it.  If  the  cannula  is  to  be  inserted  into  the  central 
end  of  the  artery,  tie  the  ligature  which  is  farthest  from  the  heart, 
and  cut  one  end  short.  Then  between  the  heart  and  the  other 
ligature  compress  the  artery  with  a  small  clamp  (often  spoken  of  as 
'  bulldog  '  forceps).  Now  lift  the  artery  by  the  distal  ligature,  make  a 
transverse  slit  in  it  with  a  pair  of  fine  scissors,  insert  the  cannula,  and 
tie  the  ligature  over  its  neck.  Cut  the  ends  of  the  ligature  short.  If 
the  cannula  is  to  be  put  into  the  distal  end  of  the  artery-,  both  ligatures 
must  be  between  the  clamp  and  the  heart,  and  the  bulldog  must  be  put 
on  before  the  first  ligature  (the  one  nearest  the  heart)  is  tied,  so  that 
the  piece  of  bloodvessel  between  it  and  the  ligature  may  be  full  of 
blood,  as  this  facilitates  the  opening  of  the  artery. 

(3)  Run  into  a,  3,  and  7  enough  blood  to  fill  them  to  the  mark. 
Shake  the  vessels,  or  stir  up  once  or  twice  with  a  glass  rod,  to  mix  the 
blood  and  solution. 

(4)  Take  a  small  thin  copper  or  brass  vessel,  and  place  it  in  a  freezing 
mixture  of  ice  and  salt.  Run  into  it  some  of  the  blood  from  the  artery-. 
It  soon  freezes  to  a  hard  mass.  Now  take  the  vessel  out  of  the 
freezing  mixture  and  allow  the  blood  to  thaw.  It  will  be  seen  that  it 
remains  liquid  for  a  short  time  and  then  clots. 

(5)  Run  some  of  the  blood  into  a  porcelain  capsule,  stirring  it 
vigorously  with  a  glass  rod.  The  fibrin  collects  on  the  rod;  the  blood 
is  defibrinated  and  will  no  longer  clot. 

(6)  Now  let  some  blood  run  into  a  small  beaker  or  jar.  Notice  that 
the  blood  begins  to  clot  in  a  few  minutes,  and  that  soon  the  vessel 
can  be  tilted  without  spilling  it.  Note  the  time  required  for  clotting 
to  occur.  Set  the  coagulated  blood  aside,  and  observe  next  day  that 
clear  yellow  serum  has  separated  from  the  clot. 

(7)  Weigh  out  a  quantity  of  Witte's  '  peptone  '  equivalent  to 
0-5  gramme  for  every  kilo'  of  body- weight  of  the  dog.  Dissolve  the 
peptone  in  about  twenty  times  its  weight  of  0*9  per  cent,  salt  solution. 
Put  a  cannula  into  the  central  end  of  a  crural  vein  (p.  211).  Fill  the 
cannula  with  the  peptone  solution  and  connect  it  with  a  burette.  Put 
15  drops  of  the  peptone  solution  into  a  test-tube  labelled  '  Peptone  A.' 
Put  the  rest  into  the  burette,  and  see  that  the  connecting  tube  is  filled 
with  the  solution  and  free  from  air.  Run  into  the  test-tube  about 
5  c.c.  of  blood  from  the  cannula  in  the  carotid.  Now  let  the  peptone 
solution  flow  from  the  burette  into  the  vein.  Feel  the  pulse  over  the 
heart  as  the  solution  is  running  in.  If  the  heart  becomes  very  weak, 
stop  the  injection ;  otherwise  the  animal  may  die  from  the  great  lower- 
ing of  blood-pressure  (p.  214).  As  soon  as  the  injection  is  finished, 
draw  off  a  sample  of  5  c.c.  of  blood  into  a  test-tube  labelled  '  Pep- 
tone B,'  and  let  it  stand.  In  ten  minutes  collect  five  further  samples 
of  5  c.c.  ('  Peptone  C,  D,  E,  F,  G  '),  and  a  large  one,  H;  in  half  an  hour 

*  One  to  2  centigrammes  of  morphine  hydrochlorate  per  kilogramme  of 
body-weight  should  be  injected  subcutaneously  about  half  an  hour  before 
the  operation.  Ten  c.c.  of  a  2  per  cent,  solution  is  sufficient  for  a  dog  of 
good  size.  Note  that  diarrhoea  and  salivation  are  caused  by  sucli  a  dose. 
For  directions  for  fastening  the  dog  on  the  holder,  see  footnote  on  p.  199. 

t  A  mixture  of  i  part  of  alcohol,  2  of  ether,  and  3  of  chloroform. 


64 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


another  set  of  five  small  samples,  and  at  as  long  an  interval  as  possible 
thereafter  five  more.  Now  letting  the  dog  bleed  to  death,  observe  that 
the  flow  of  blood  is  temporarily  increased  by  pressure  on  the  abdominal 
walls,  which  squeezes  it  towards  the  heart,  by  passive  movements  of 
the  hind-legs,  and  also  during  the  convulsions  of  asphyxia,  which  soon 
appear.  Add  to  the  peptone  blood  D  5  c.c.  of  serum,  to  E  a  little 
sodium  chloride  extract  of  liver,  to  F  a  little  extract  of  muscle,  and  to 
G  15  drops  of  a  2  per  cent,  solution  of  calcium  chloride,  and  put  C,  D, 
E,  F,  and  G  into  a  water-bath  at  40°  C.     Treat  the  other  sets  of  small 

samples  in  the  same  way.  Note 
how  long  each  specimen  takes  to 
clot,  and  report  your  results.* 

(8)  Observe  that  the  blood  in  a, 
8,  and  y  has  not  coagulated.  Label 
four  test-tubes  '  Oxalate  A,  B,  C, 
D,'  and  put  into  each  about  5  c.c. 
of  the  oxalated  blood.  Add  to  A 
and  B  5  or  6  drops  of  a  2  per  cent, 
solution  of  calcium  chloride,  to  C  12 
drops,  and  to  D  as  much  as  there 
is  of  the  blood.  Leave  A  at  the 
ordinary  temperature,  put  the  other 
test-tubes  in  a  water-bath  at  40°  C, 
and  note  when  clotting  occurs. 

(9)  To  10  c.c.  of  the  fluoride  blood 
add  a  little  more  CaClj  than  is  re- 
quired to  combine  with  the  excess 
of  fluoride  present.  Label  four  test- 
tubes  '  Fluoride  A,  B,  C,  D,'  and 
into  each  put  about  2  c.c.  of  this 
'  recalcified  '  fluoride  blood.  To  B 
add  I  c.c.  liver  extract,  to  C  i  c.c. 
muscle  extract,  and  to  D  4  c.c. 
water.  Label  two  more  test-tubes 
'  Fluoride  E  and  F.'  Into  each  put 
2  c.c.  of  the  fluoride  blood  without 
CaCl2.  '  Add  also  to  E  i  c.c.  liver 
extract  and  to  F  i  c.c.  serum.  Put 
all  the  tubes  in  a  bath  at  about 
40°  C,  and  observe  in  which  and  in 
what  time  coagulation  takes  place. 

(10)  By  means  of  a  centrifuge 
(Fig.  17)  separate  the  plasma  from 
the  corpuscles  in  a,  13,  and  y,  and 
also  from  the  peptone  blood. 

With  the  oxalate  plasma  from  ^, 
and  the  fluoride  plasma  from  y,  repeat  the  observations  in  (8)  and 
(9),  using  smaller  quantities  of  the  plasma,  if  necessary,  in  small  test- 
tubes.  With  the  plasma  from  a  perform  the  following  experiments : 
Put  a  small  quantity  of  the  plasma  (i  c.c.)  into  four  test-tubes,  labelling 

*  Sometimes  the  injection  of  peptone  hastens  coagulation  instead  of  hinder- 
ing it.  It  has  been  asserted  that  this  is  only  the  case  when  small  doses  are 
used  (less  than  o'02  gramme  per  kilo  of  body-weight).  But  in  2  dogs  out  of 
II  a  dose  of  o'5  gramme  per  kilo  has  been  seen  to  hasten  coagulation,  and  in 
I  out  of  12  to  leave  it  unaffected;  in  the  other  9  coagulation  was  markedly 
retarded 


Fig.  17. — Centrifuge  (Jung).  The  four 
cylinders  shown  at  the  top  of  the 
figure  are  so  swung  that  they  become 
horizontal  as  soon  as  speed  is  up. 


PRACTICAL  EXERCISES  65 

them  '  Magnesium  Sulphate  A,  B,  C,  D.'  Dilute  B  with  four  times,  C 
with  eight  times,  and  D  with  twenty  times  as  much  distilled  water  as 
was  taken  of  the  plasma.  Observe  in  which,  if  any,  coagulation  occurs, 
and  the  time  of  its  occurrence,  and  report  the  result. 

(11)  With  peptone  plasma  from  H  and  from  the  peptone  blood 
obtained  later  repeat  the  experiments  done  in  (7).  In  addition  dilute 
I  c.c.  of  the  plasma  with  three  volumes  of  water  and  i  c.c.  of  it  with 
ten  volumes  of  water,  and  put  in  the  bath  at  40°  C.  Observe  whether 
clotting  occurs. 

Instead  of  dog's  blood,  the  blood  of  an  ox  or  pig  may  be  obtained  at 
the  slaughter-house. 

4.  Preparation  of  Fibrin-Ferment. — Precipitate  blood-serum  with 
ten  times  its  volume  of  alcohol.  Let  it  stand  for  several  weeks,  then 
extract  the  precipitate  with  water.  The  water  dissolves  out  the  fibrin- 
ferment,  but  not  the  coagulated  serum  proteins. 

5.  Preparation  of  Tissue  Extracts  containing  Thrombokinase. — In  a 
dog  or  rabbit  killed  by  bleeding  insert  a  cannula  into  the  lower  end  of 
the  thoracic  aorta.  Fill  the  cannula  with  0-9  per  cent,  salt  solution, 
and  connect  it  with  a  bottle  also  containing  salt  solution.  Wash 
out  the  vessels  of  the  lower  portion  of  the  body,  making  an  opening 
in  the  inferior  vena  cava  above  the  diaphragm  to  allow  the  liquid 
to  escape.  For  the  sake  of  cleanliness,  a  cannula  armed  with  a 
piece  of  rubber  tubing  should  be  inserted  for  this  purpose  into  the 
inferior  vena  cava.  Continue  the  injection  till  the  liquid  issues  colour- 
less. Then  remove  portions  of  liver  and  muscle.  Mince  each  separately. 
Rub  up  with  sand  in  a  mortar.  Add  o-g  per  cent,  sodium  chloride 
solution  and  rub  up  again.  Put  into  bottles  and  keep  in  the  ice-chest. 
For  use  take  off  some  of  the  liquid  from  the  top  with  a  pipette,  or  strain 
through  cheese-cloth. 

6.  Serum. — Test  the  reaction,  and  determine,  both  by  the  hydrom- 
eter and  the  pycnometer,  or  specific  gravity  bottle,  the  specific 
gravity  of  the  serum  provided,  or  of  the  serum  obtained  in  experi- 
ment 3. 

Serum  Proteins. — (i)  Saturate  serum  with  magnesium  sulphate 
cr^-stals  at  30°  C.  The  serum-globulin  is  precipitated.  Filter  off. 
Wash  the  precipitate  on  the  filter  with  a  saturated  solution  of  mag- 
nesium sulphate.  Dissolve  the  precipitate  by  the  addition  of  a  little 
distilled  water,  and  perform  the  following  tests  .for  globulins :  (a)  Satu- 
rate with  magnesium  sulphate.  A  precipitate  is  obtained,  (b)  Drop 
into  a  large  quantity  of  water,  and  a  flocculent  precipitate  falls  down. 
{c)  Heat.  Coagulation  occurs.  Determine  the  temperature  of  coagu- 
lation (p.  9). 

(2)  To  a  portion  of  the  filtrate  from  (i)  add  sodium  sulphate  to 
saturation.  The  serum-albumin  is  precipitated.  (Neither  magnesium 
sulphate  nor  sodium  sulphate  precipitates  serum-albumin  alone,  but 
the  double  salt  sodio-magnesium  sulphate  precipitates  it,  and  this  is 
formed  when  sodium  sulphate  is  added  to  magnesium  sulphate.) 

(3)  Dilute  another  portion  of  the  filtrate  from  (i)  with  its  own  bulk 
of  water.  Very  slightly  acidulate  with  dilute  acetic  acid,  and  de- 
termine the  temperature  of  licat  coagulation. 

(4)  Precipitate  the  serum-globulin  from  another  portion  of  serum  by 
adding  to  it  an  equal  volume  of  saturated  solution  of  ammonium 
sulphate.  Filter.  Precipitate  the  serum-albumin  from  the  filtrate  by 
saturating  with  ammonium  sulphate  crystals. 

(5)  Dilute  serum  with  ten  to  twenty  times  its  volume  of  distilled 
water,  and  pass  through  it  a  stream  of  carbon  dioxide.  The  scrum- 
globulin  is  partially  precipitated. 

5 


66  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

(6)  Acidulate  some  serum  with  dilute  acetic  acid  and  boil.  Filtej 
off  the  coagulum,  and  to  the  filtrate  add  silver  nitrate.  A  non-protein 
precipitate  insoluble  in  nitric  acid,  but  soluble  in  ammonia,  indicates 
the  presence  of  chlorides. 

7.  Action  of  Serum  on  Artery  Rings. — Cut  a  number  of  rings  about 
i\  millimetres  wide  from  a  fresh  carotid  artery  of  the  sheep,  obtained 
from  the  slaughter-house.  Keep  the  rings  in  a  dish  in  Ringer's  solu- 
tion.* They  should  be  as  nearly  as  possible  of  uniform  width.  A  small 
cylindrical  glass  vessel  is  supported  on  a  stand  in  such  a  way  that  it 
can  be  easily  lowered  into  a  bath  of  water  kept  at  a  temperature  of 
about  39°  to  40°.  A  stock  of  Ringer's  solution  is  kept  in  a  beaker 
or  bottle  immersed  in  the  bath.  A  ring  of  the  artery  is  put  into  the 
small  cylinder,  where  it  is  held  between  two  aluminium  hooks,  one 
fastened  to  the  bottom  of  the  cylinder,  the  other  (the  upper  one)  con- 
nected with  the  short  arm  of  a  lever,  the  long  arm  of  which  is  arranged 
to  write  on  a  slowly  revolving  drum.  A  time-trace,  say  in  half- 
minutes,  is  recorded  below.  The  small  cylinder  is  now  filled  with 
warm  Ringer's  solution  and  lowered  into  the  bath.  Oxygen  is  bubbled 
through  the  solution  by  means  of  a  side-tube  near  the  bottom  of  the 
cylindrical  vessel.  The  artery  ring  is  now  stretched  for  five  minutes 
by  a  weight  of  10  grammes  attached  to  the  long  arm  of  the  lever  at  the 
same  distance  from  the  axis  as  that  at  which  the  ring'  is  attached. 
After  the  stretching  period  the  weight  is  removed,  and  a  little  time 
allowed  to  elapse  till  the  writing-point  traces  a  horizontal  line  on  the 
drum.  Then  a  bent  pipette  is  filled  with  serum  already  heated  to  bath 
temperature  in  a  vessel  immersed  in  the  bath.  The  pipette  is  intro- 
duced into  the  small  cylinder  so  that  its  point  is  at  the  bottom,  without 
disturbing  the  ring,  and  the  serum  is  allowed  to  run  in  till  the  Ringer 
solution  is  displaced.  The  ring  shortens  under  the  influence  of  the  con- 
strictor substance  in  the  serum,  and  the  tracing  is  continued  till  the 
shortening  has  reached  its  maximum  and  the  trace  is  again  horizontal 
(Fig.  3,  p.  40). 

Various  dilutions  of  the  serum  are  now  made  with  Ringer's  solution, 
and  the  greatest  dilution  in  which  the  serum  will  still  cause  a  percep- 
tible constriction  of  the  rings  is  determined.  This  affords  a  measure 
of  comparison  with  other  sera  of  the  strength  of  the  constrictor  action. 
For  each*dilution  of  serum  a  separate  ring  must  be  used.  It  must  be 
remembered  that  comparisons  of  this  kind  can  only  be  made  with 
arteries  of  the  same  sensitiveness,  and  different  arteries  vary  much  in 
this  regard. 

8.  Comparison  of  the  Action  of  Serum  and  Adrenalin  (Epinephrin)  on 
Artery  Rings. — Tracings  showing  the  effect  of  various  dilutions  of 
adrenalin  chloride  on  artery  rings  may  now  be  taken  for  comparison 
with  the  serum  effects.  The  adrenalin  dilutions  should  be  made  just 
before  use,  as  adrenalin  is  rapidly  oxidized.  Or  a  separate  experiment 
on  the  action  of  adrenalin  may  be  made  under  '  Circulation,'  as  on 
p.  214. 

9.  Comparison  of  the  Action  of  Serum  and  Plasma  on  Artery  Rings. — 
Citrate  plasma  is  obtained  as  follows :  A  cannula  and  attached  rubber 
tube  are  boiled,  oiled  inside  with  fresh  olive-oil,  and  filled  with  a  citrate 

*  This  is  the  name  given  to  a  solution  containing  the  most  important  of 
the  inorganic  constituents  of  blood -serum  in  approximately  the  normal  pro- 
portions. The  various  '  Ringer's  solutions  '  used  by  different  workers  have 
varied  slightly.  That  recommended  by  Locke  (for  perfusion  of  the  isolated 
heart)  contains  NaCl,  0*9  per  cent.;  KCl,  0-042  per  cent.;  CaCl2,  0-024  per  cent.; 
Na}IC03,  o-oi  to  0-03  per  cent.;  with  in  addition  o"i  per  cent,  of  dextrose, 
whxh  can  be  omitted  for  such  experiments  as  7. 


PRACTICAL  EXERCISES 


67 


solution  made  by  dissolving  sodium  citrate  in  Ringer's  solution  to  the 
extent  of  2  per  cent.  The  solution  is  prevented  from  escaping  by  a 
clip  on  the  tube.  The  cannula  is  inserted  into  the  carotid  of  a  dog, 
the  end  of  the  rubber  tube  dipped  below  a  quantity  of  citrate- 
Ringer  solution  in  a  beaker,  and  a  volume  of  blood  equal  to  that  of  the 
solution  run  in.  Then  the  blood  and  solution  are  at  once  stirred  gently, 
but  sufiiciently  to  insure  proper  admixture. 

Some  blood  is  now  run  into  another  vessel,  defibrinated,  and 
measured.  An  equal  volume  of  the  citrate-Ringer  solution  is  added  to 
it  while  the  mass  of  fibrin  is  still  floating  in  the  blood.  After  mixing, 
the  fibrin  is  removed.  Plasma  is  then  separated  by  the  centrifuge  from 
the  first  specimen  of  blood,  and  serum  from  the  second,  and  comparison 
experiments  are  made  with  each  on  artery  rings.  If  the  plasma  has 
been  properly  obtained,  it  will  have  little  constrictor  effect  on  the 
rings  in  comparison  with  the  serum.  In  making  the  comparison, 
arteries  which  give  a  decided  effect  with  serum  should  be  employed. 
The  defibrinated  blood  and  the  unclotted  citrate  blood  may  also  be 
used  for  tlic  comparison. 


Fig.  18.  —  Thoma-Zeiss  Haemocytometer.  M,  mouthpiece  of  tube  G,  by  which 
blood  is  sucked  into  S;  E,  bead  for  mixing;  a,  view  of  slide  from  above;  b,  in 
section;  c,  squares  in  middle  of  B,  as  seen  under  microscope. 

10.  Enumeration  of  the  Blood  -  Corpuscles.  —  Use  the  Thoma-Zeiss 

apparatus  (Fig.  18).  (i)  Suck  a  drop  of  ox  or  dog's  blood  up  into 
the  capillary  tube  S  to  the  mark  i.  Wipe  off  any  blood  which 
may  adhere  to  the  end  of  the  tube.  I'hen  fill  it  with  3  per 
cent,  sodium  chloride  to  the  mark  loi.  This  represents  a  dilution  of 
100  times.  Mix  the  blood  and  solution  thoroughly,  then  blow  out  a 
drop  or  two  of  the  liquid  to  remove  all  the  solution  which  remains  in 
the  capillary  tube.  Now  fill  the  shallow  cell  B  with  the  blood  mixture. 
Put  the  cover-glass  on,  taking  care  that  it  does  not  float  on  the  liquid, 
but  that  the  cell  is  exactly  filled.  Put  the  slide  under  the  microscope 
(say  Leitz's  oc.  III.,  obj.  5),  and  count  the  number  of  red  corpuscles 
in  not  less  than  ten  to  twenty  squares.  Sixteen  squares  is  a  good 
routine  number.  The  greater  the  number  of  squares  counted,  the 
nearer  will  be  the  approximation  to  the  truth.  Now  take  the  average 
number  in  a  square.  The  depth  of  the  cell  is  ,V  mm.,  the  area  of  each 
square  ^,\,7  sq.  mm.  The  volume  of  the  column  of  liquid  standing 
upon  a  square  is  .,j}-(ij-,  cub.  mm.  One  cub.  mm.  of  the  diluted  blood 
would  therefore  contain  4,000  times  as  many  corpuscles  as  one  square. 
Bat  the  blood  has  been  diluted  100  times,  therefore  i  cub.  mm.  of  the 


68 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


undiluted  blood  would  contain  400,000  times  the  number  of  corpuscles 
in  one  square.  Suppose  the  average  for  a  square  is  found  to  be  13. 
This  would  correspond  to  5,200,000  corpuscles  in  i  cub.  mm.  of  blood. 
Compare  3'our  result  with  the  true  number  supplied  by  the  demon- 
strator. (2)  Prick  the  finger  to  obtain  a  drop  of  blood,  and  repeat 
the  count  as  in  (i).* 

To  Count  the  White  Corpuscles. — Add  to  i  part  of  blood  9  parts  of 
\  per  cent,  acetic  acid,  in  order  to  lake  the  coloured  corpuscles  and 
render  it  easy  to  see  the  leucocytes. 

II.  Relative  Volume  of  Corpuscles  and  Plasma  by  Haematocrite. — 
(i)  For  practice,  fill  the  two  graduated  glass  tubes  with  the  defibrinated 
blood  of  an  animal.  The  rubber  tube  with  mouthpiece  supplied  with 
the  apparatus  is  to  be  attached  to  the  glass  tube,  and  the  blood  sucked 
up.  Press  the  tip  of  the  index-finger  against  the  pointed  end,  and  care- 
fully remove  the  rubber  tube.  Place  the  tube  in  the  haematocrite  frame, 
blunt  end  outwards — that  is,  farthest  from  the  axis  of  rotation — and 
then  slip  the  pointed  end  down  into  position  against  the  spring.  Instead 
of  the  rubber  tube,  a  special  suction  pipette  for  automatically  filling 
the  graduated  tubes  may  be  employed  (Daland).  Attach  the  haemato- 
crite frame  to  the  centrifuge,  and  rotate  till  the  volume  of  sediment 


Fig.  19. 


-Haematocrite.      A,  haematocrite  attachment  with  graduated  tubes;  B,  auto- 
matic pipette  for  filling  the  tubes  (Daland). 


(corpuscles)  ceases  to  diminish.  The  graduations  are  best  read  with  a 
hand  lens.  The  leucocytes  will  be  seen  to  form  a  thin  whitish  line 
proximal  to  the  column  of  red  corpuscles. 

(2)  F*rick  the  finger  or  the  lobe  of  the  ear,  fill  the  tubes  as  in  (i),  and 
centrifugalize.  Everything  must  be  done  as  rapidly  as  possible,  so 
that  the  blood  may  not  clot  till  the  separation  of  plasma  and  corpuscles 
is  completed.  The  centrifuge  must  rotate  very  rapidly  (about  10,000 
revolutions  a  minute)  for  two  or  three  minutes.  For  clinical  purposes 
it  is  best  to  rotate  the  centrifuge  always  at  the  same  speed  for  the 
same  length  of  time  rather  than  to  aim  at  reaching  a  constant  length 
of  the  column  of  corpuscles.  In  this  way  useful  comparative  results 
can  be  obtained.  It  is  well,  to  avoid  the  risk  of  accident,  to  rotate  the 
centrifuge  imder  a  guard. 

12.  Electrical  Conductivity  of  Blood. — (i)  Fill  a  small  U-tube  with 
blood  up  to  a  mark.     In  each  limb  insert  a  platinum  electrodef  con- 

*  If  the  tube  has  not  been  properly  filled,  blow  the  blood  out  immediately. 
On  no  account  permit  it  to  clot  in  the  capillary  tube. 

t  if  the  platinum  electrodes  are  of  good  size  and  the  resistance  of  the  tube 
of  liquid  considerable,  it  is  not  necessary  to  platinize  them — i.e.,  to  cover  them 
by  electrolysis  of  a  solution  of  platinic  chloride  witu  a  layer  of  platinum-black. 


PRACIICAL  EXERCISES  69 

nected  with  a  holder,  which  insures  that  the  electrode  shall  always  dip 
to  the  same  depth  into  the  tube.  Arrange  the  U-tube  so  that  it  is 
immersed  at  least  to  the  mark  in  water  of  constant  temperature.  Water 
running  freely  from  the  cold-water  tap  into  and  out  of  a  large  vessel 
will  have  a  sufficiently  constant  temperature  for  the  purpose.  A  ther- 
mometer must  be  fixed  in  the  water  with  its  bulb  in  contact  with  the 
U-tube.  Connect  the  electrodes  with  a  resistance-box  in  the  Wheat- 
stone's  bridge  arrangement  (Fig.  220,  p.  699),  so  that  the  U-tube 
occupies  the  position  of  the  unknown  resistance  CD.  Instead  of  the 
battery  F,  cormect  the  poles  of  the  secondary  of  a  small  induction-coil, 
arranged  for  an  interrupted  current,  with  A  and  C,  and  instead  of  the 
galvanometer  G  insert  a  telephone.  The  resistances  AB  and  AD  will 
be  obtained  by  taking  out  two  plugs  from  the  appropriate  part  of  the 
resistanoe-box.  Whether  AB  and  AD  should  be  equal  (say,  10  :  10, 
100  :  100,  or  1,000  :  1,000  ohms)  or  unequal  (say,  10  :  100,  or 
100  :  1,000,  or  10  :  1,000  ohms)  will  depend  upon  the  resistance  of 
the  tube  of  liquid  to  be  measured.  Take  out  from  the  part  of  the  box 
corresponding  to  BC  a  plug  representing  a  resistance  something  like 
that  which  the  tube  of  blood  is  expected  to  have.  Close  the  primary 
circuit  of  the  indu».tion-coil,  and  apply  the  telephone  to  the  ear.  A 
buzzing  sound  will  be  heard,  which  will  be  louder  the  farther  from  the 
true  resistance  of  the  tube  the  resistance  taken  out  of  the  box  is.  Go 
on  altering  the  resistance  in  the  box  by  taking  out  or  putting  in  plugs 
till  the  sound  disappears,  or  is  reduced  to  a  minimum.  The  tempera- 
ture of  the  water  should  now  be  read  off.  The  resistance  of  the  tube  of 
blood  for  this  temperature  can  easily  be  calculated  from  the  formula 
on  p.  699.  It  increases  about  2  per  cent,  for  each  degree  Centigrade  of 
diminution  of  temperature.  The  conductivity  is  the  reciprocal  of  the 
resistance.  By  determining  once  for  all  the  resistance  of  the  tube 
when  filled  with  a  standard  solution  of  a  salt  whose  conductivity  is 
known,  the  specific  conductivity  of  the  blood  can  be  expressed  in 
definite  units,  but  this  is  not  necessary  for  the  purposes  of  the  student. 
Compare  the  resistances  of  defibrinated  blood,  serum,  0-9  per  cent, 
sodium  chloride  solution,  and  a  sediment  of  blood-corpuscles  separated 
by  centrifugalization. 

(2)  Instead  of  the  resistance-box  a  wire  mounted  on  a  scale  may  be 
used  for  the  resistances  AB,  AD,  the  ends  of  the  wire  being  connected 
at  B  and  D.  A  slider  with  an  insulated  handle  moving  along  the 
graduated  wire  is  joined  by  a  flexible  wire  with  one  pole  of  the  secondary 
coil,  the  other  pole  being  connected  at  C.  The  resistance  BC  is  consti- 
tuted by  a  rheostat  from  which  a  fixed  resistance  can  be  taken  out. 
Instead  of  obtaining  the  minimum  sound  in  the  telephone  by  varying 
the  resistance  BC  in  the  box,  the  measurement  is  made  by  var\-ing  the 
position  of  the  slider;  in  other  words,  by  changing  the  ratio  AB:  AD. 

(3)  If  no  rheostat  is  available  instructive  comparative  measurements 
may  still  be  made  with  the  graduated  wire  by  substituting  for  the 
resistance  BC  a  U-tube  of  another  liquid. 

If  the  tubes  are  of  the  same  dimensions,  and  the  liquids  with  which 
they  are  filled  are  approximately  at  the  same  initial  temperature,  it 
is  not  necessary'  to  immerse  them  in  water  at  constant  temperature.  It 
is  sufficient  to  place  them  side  by  side  in  the  air.  Perform  the  following 
experiments  in  this  way: 

(a)  Label  the  tubes  A  and  B.  Fill  them  both  to  the  mark  with 
0-9  per  cent.  NaCl  solution.  Connect  as  in  the  figure,  and  move  the 
slider  along  the  wire  tUl  the  sound  is  a  minimum.  Probably  the  two 
tubes  arc  not  exactly  of  the  same  dimensions,  and  therefore  the  slider 
will  not  be  exactly  in  the  middle  of  the  wire.      Suppose  it  is  at  49-0 


70  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

the  total  length  of  the  wire  being  loo.     Then  resistance  of  A :  resistance 

of  B::  4Q'0 :  si-o,  i.e.,  resistance  of  A  =  —  resistance  of  B. 

(6)  Fill  A  with  defibrinated  blood,  keeping  B  filled  with  NaCl  solu- 
tion, and  repeat  the  measurement.  The  slider  must  now  be  moved 
much  farther  away  from  the  zero  of  the  scale.  Suppose  the  minimum 
sound  is  obtained  with  the  slider  at  70*0.     Then  resistance  of  blood  = 

2  X  —  resistance  of  the  NaCl  solution. 
7     49 

(c)  Compare  in  the  same  way  the  resistance  of  serum  with  that  of 
the  NaCl  solution.     It  will  be  found  much  less  than  that  of  the  blood. 

(d)  Centrifugalize  some  of  the  blood  for  as  long  as  is  convenient,  and 
compare  the  resistance  of  the  blood  from  the  top  of  the  tubes  and  from 
the  bottom  of  the  tubes  with  that  of  the  NaCl  solution.  The  resistance 
of  the  blood  from  the  bottom  of  the  tubes  will  be  found  much  greater 
than  that  of  the  blood  from  the  top. 

13.  Opacity  of  Blood. — Smear  a  little  fresh  blood  on  a  glass  slide,  and 
hold  the  slide  above  some  printed  matter.  It  will  not  be  possible  to 
read  it,  because  the  light  is  reflected  from  the  corpuscles  in  all  directions, 
and  little  of  it  passes  through. 

14.  Laking  of  Blood  by  Chemical  and  Physical  Agents. — (i)  Put  a 
little  fresh  blood  into  three  test-tubes,  A,  B,  and  C.  Dilute  A  with  an 
equal  volume,  B  with  two  volumes,  and  C  with  three  volumes,  of  dis- 
tilled water,  and  repeat  experiment  9.  The  print  can  now  be  read 
probably  through  a  layer  of  A,  but  certainly  through  B  and  C,  since 
the  haemoglobin  is  dissolved  out  of  the  corpuscles  by  the  water  and 
goes  into  solution,  the  blood  becoming  transparent  or  laked.  That  the 
difference  is  not  due  merely  to  dilution  can  be  shown  by  putting  an 
equal  quantity  of  blood  in  two  test-tubes,  and  gradually  diluting  one 
with  distilled  water  and  the  other  with  a  0-9  per  cent,  solution  of 
sodium  chloride,  which  does  not  dissolve  out  the  haemoglobin.  Print 
can  be  read  through  the  first  with  a  smaller  degree  of  dilution  than 
through  the  second.  Examine  the  laked  blood  with  the  microscope 
for  the  '  ghosts,'  or  shadows  of  the  red  corpuscles.  The  addition  of  a 
drop  or  two  of  methylene  blue  will  render  them  somewhat  more  distinct. 

(2)  Heat  a  little  dog's  or  ox  blood  in  a  test-tube  immersed  in  a  water- 
bath.  Put  a  thermometer  in  the  test-tube,  taking  care  that  there  is 
enough  blood  to  cover  the  bulb.  Keep  the  temperature  about  60°  C. 
In  a  few  minutes  the  blood  becomes  dark  and  laking  occurs. 

(3)  (rt)  Put  a  little  blood  into  each  of  four  test-tubes.  To  one  add  a 
little  ether,  to  another  a  little  chloroform,  to  the  third  dilute  acetic 
acid  in  0*9  per  cent.  NaCl,  and  to  the  fourth  a  dilute  solution  of  bile 
salts  (or  of  sodium  taurocholate)  in  0*9  per  cent.  NaCl  solution.  Laking 
occurs  in  all. 

(6)  To  5  c.c.  of  blood  add  0*5  c.c.  of  a  3  per  cent,  solution  of  saponin 
in  0'9  per  cent.  NaCl  solution,  and  put  the  mixture  at  40°  C.  Laking 
soon  occurs. 

(c)  Using  a  10  per  cent,  dilution  of  blood  (blood  to  which  nine  volumes 
of  NaCl  solution  have  been  added)  or  a  5  per  cent,  suspension  of  washed 
corpuscles  in  NaCl  solution  {i.e.,  a  suspension  of  corpuscles  which  have 
been  washed  free  from  serum  by  being  repeatedly  mixed  with  NaCl 
solution  and  centrifugalized),  determine  the  minimum  dose  of  0-3  per 
cent,  saponin  solution  which  will  just  cause  complete  laking.  Keep  the 
tubes  at  about  40°  C,  and  observe  them  from  time  to  time.  Now  add 
to  some  of  the  10  per  cent,  dilution  or  the  5  per  cent,  suspension  of  blood 
an  equal  volume  of  serum  from  the  same  kind  of  blood,  and  repeat  the 
determination  of  the  minimum  dose  of  saponin  necessary  for  laking. 


PRACTICAL  EXERCISES  71 

It  will  be  found  that  more  is  now  required.     The  cholesterin  in  the 
serum  neutralizes  the  action  of  some  of  the  saponin. 

(4)  (a)  Put  I  c.c.  of  blood  into  each  of  two  test-tubes.  To  one  add 
1  c.c.  of  2  per  cent,  aqueous  solution  of  urea,  and  to  the  other  3  c.c. 
Laking  will  take  place  in  the  second,  whether  this  has  been  the  case  in 
the  first  or  not. 

{b)  Repeat  the  experiment  with  a  2  per  cent,  solution  of  urea  in 
0-9  per  cent.  NaCl  solution.  Laking  docs  not  occur.  This  shows  that 
the  urea  in  the  first  experiment  did  not  act  as  a  hemolytic  agent. 
Laking  occurred  because  urea  penetrates  the  corpuscles  easily,  and 
therefore,  although  the  freezing-point  of  the  urea  solution  is  not  ver^' 
different  from  that  of  the  NaCl  solution,  its  actual  osmotic  pressure, 
in  relation  to  the  envelopes  of  the  corpuscles,  is  very  much  less,  and  the 
laking  is  really  water-laking. 

(5)  Put  some  blood  into  a  flask  or  test-tube,  cork  up,  and  let  it  stand 
till  it  begins  to  putrefy.  It  becomes  laked.  The  same  occurs  when 
the  blood  is  collected  aseptically  in  a  sterile  tube  and  sealed  up,  although 
it  takes  a  longer  time  for  the  laking  to  become  complete. 

(6)  With  blood  containing  nucleated  corpuscles  (necturus,  frog  or 
chicken)  diluted  with  isotonic  salt  solution,  perform  the  following 
experiments  under  the  microscope  : 

(a)  With  a  glass  rod  drawn  to  a  fine  point  put  a  small  drop  of  blood 
on  a  slide,  and  near  it  a  drop  of  distilled  water.  Carefully  lower  the 
cover-slip  and  observe  the  interface  with  the  microscope,  first  with  thti 
low  and  then  with  the  high  power.  Then  mix  and  see  complete  laking. 
Add  a  little  methylene  blue.     Note  that  the  nuclei  still  stain. 

{b)  Place  a  small  drop  of  a  3  per  cent,  solution  of  saponin  in  isotonic 
salt  solution  on  a  slide,  and  near  it  a  small  drop  of  blood.  Observe  as 
in  (a).  Repeat  with  a  2  per  cent,  solution  of  sodium  taurocholate  in 
salt  solution.  If  necturus  corpuscles,  which  are  splendid  objects  for 
such  experiments  on  account  of  their  great  size,  have  been  used, 
intracorpuscular  crystallization  of  the  haemoglobin  may  be  observed. 

(c)  Repeat  [a)  and  (5)  with  mammalian  blood.  Note  that  the  cor- 
puscles swell  before  being  laked  by  the  saponin.  If  any  of  the  corpuscles 
are  crenated,  it  may  be  seen  that  before  being  laked  by  the  saponin 
the  crenations  disappear,  the  corpuscles  becoming  round,  while  in  the 
taurocholate  solution  they  may  remain  crenated  till  laking  has  occurred. 
This  indicates  that  the  permeability  of  the  envelopes  is  not  affected  in 
the  same  way  by  the  two  laking  agents. 

15.  Haemolysis  and  Agglutination  by  Foreign  Serum. — (i)  To  a  small 
quantity  of  rabbit's  blood  add  an  equal  volume  of  dog's  serum.  Mix 
and  let  stand  at  40°  C.  The  colour  of  the  blood  is  soon  darker  than 
before,  and  it  can  be  seen  to  be  laked.     Examine  microscopically. 

(2)  Place  a  small  drop  of  rabbit's  blood  and  a  somewhat  larger  drop 
of  the  dog's  serum  on  a  slide,  near,  but  not  quite  in  contact  with,  each 
other.  Now  put  on  a  cover-slip,  so  that  the  drops  just  come  together, 
and  examine  at  once  with  the  microscope  with  a  moderately  high  power. 
Where  the  two  drops  mingle,  the  red  corpuscles  will  be  seen  first  to 
become  agglutinated  into  groups,  and  then  to  fade  out,  leaving  only 
their  '  ghosts.'  A  few  of  the  corpuscles  which  come  into  contact  with 
the,  as  yet,  undiluted  serum  may  be  entirely  dissolved. 

(3)  Heat  some  of  the  dog's  serum  to  60°  C.  for  ten  minutes,  and 
repeat  (i)  and  (2).  No  laking  will  now  be  produced  in  the  rabbit's 
corpuscles,  but  agglutination  may  be  observed  as  before. 

(4)  Repeat  (i)  and  (2)  with  dog's  blood  and  rabbit's  serum.  The 
blood  will  not  be  laked.  although  sometimes  the  dog's  corpuscles  may 
become  crenated.     There  will  be  no  agglutination. 


72  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

(5)  With  a  5  per  cent,  suspension  of  rabbit's  washed  corpuscles 
perform  the  following  experiments:* 

Put  into  each  of  six  small  test-tubes  i  c.c.  of  the  suspension.  Label 
the  tubes  A,  A',  B,  B',  C,  C. 

{a)  To  A  and  A'  add  respectively  o-i  c.c.  and  0-5  c.c.  ox  serum. 

{b)  To  B  and  B'  add  respectively  o-i  ex.  and  0-5  c.c.  dog's  serum. 

(c)  To  C  and  C  add  respectively  o-i  c.c.  and  0-5  c.c.  of  0-9  per  cent, 
sodium  chloride  solution. 

Put  all  the  tubes  in  a  bath  at  40°  C.  Compare  the  amount  of  laking 
and  agglutination  in  the  various  tubes  at  intervals  of  two  minutes  or 
less.  Repeat  (a),  [b),  and  (c)  with  guinea-pig's  washed  corpuscles  and 
serum  of  ox  and  dog.  Determine  which  of  these  sera  has  the  strongest 
hsemolytic  power. + 

(6)  Heat  i  c.c.  o:f  ox  and  dog's  serum  respectively  to  56°  C,  keeping 
it  at  that  temperature,  or  not  more  than  a  couple  of  degrees  above  it, 
for  ten  J  minutes,  and  repeat  experiment  (5),  labelling  the  tubes  D,  D', 
E,  E',  F,  F'.  Save  the  rest  of  the  heated  sera  for  (8).  There  is  no 
laking  in  any  of  the  tubes,  but  probably  agglutination  in  D,  D',  and 
E,  E'.  (The  complement  is  destroyed,  but  not  the  intermediary  body 
or  amboceptor,  or  the  agglutinin — p.  28.) 

(7)  Put  half  of  the  contents  of  tubes  D,  D',  E,  E',  into  four  separate 
test-tubes,  and  add  to  each  0-2  c.c.  of  rabbit's  serum.  If  there  is  laking 
now  it  is  because  the  rabbit's  serum  contains  complement.  Save  the 
balance  of  D,  D',  E  and  E'  for  (8). 

(8)  Allow  0'5  c.c.  of  ox  serum  to  act  at  0°  C.  on  the  rabbit's  washed 
corpuscles  contained  in  5  c.c.  of  the  5  per  cent,  suspension  after  removal 
of  the  sodium  chloride  solution.  The  ox  serum  and  rabbit's  corpuscles 
are  separately  cooled  to  0°  C.  before  being  mixed,  and  the  mixture  is 
then  kept  at  0°  C.  for  one  hour.  Centrifugalize  the  serum  off  rapidly. 
Label  it  '  Serum  S.'  To  0-2  c.c.  of  the  original  5  per  cent,  suspension 
of  rabbit's  washed  corpuscles  add  o-i  c.c.  of  this  serum  (labelling  the 
tube  G),  and  put  at  40°  C.  with  a  control-tube  containing  the  same 
amount  of  suspension  plus  salt  solution  instead  of  serum.  Add  the 
rest  of  the  serum  S,  cooled  to  0°  C,  to  the  same  cooled  rabbit's  cor- 
puscles, and  leave  for  a  furtlier  period  at  0°  C.  Then  centrifugalize 
rapidly,  and  to  0*2  c.c.  of  the  original  suspension  of  washed  rabbit's 
corpuscles  add  o-i  c.c.  of  serum  S  (labelling  the  tube  H),  and  put  at 
40°  C.   with  a  sodium  chloride  tube  as  control.     There  may  be  no 

*  The  material  obtained  from  one  medium-sized  dog,  two  rabbits,  and  one 
guinea-pig  is  enough  for  fifty  or  sixty  students,  working  together  in  sets  of 
two,  to  perform  experiments  (5)  to  (8).  In  order  to  obtain  a  serum  more 
strongly  hsemolytic  for  rabbit's  corpuscles  than  normal  dog's  serum,  a  dog 
may  be  '  immunized  '  by  previous  injection  of  all  the  washed  corpuscles 
obtainable  from  a  rabbit.  The  injection  should  be  made  under  the  skin  or, 
better,  into  the  peritoneal  cavity — of  course,  with  aseptic  precautions.  It 
should  be  repeated  not  less  than  twice,  with  an  interval  of  ten  days  between 
the  successive  injections,  and  the  dog's  blood  should  be  drawn  off  about  ten 
days  after  the  last  injection. 

f  To  determine  the  amount  of  laking  at  any  given  moment,  drop  the  small 
test-tubes  into  the  metallic  centrifuge  cups  after  shaking  them  up,  and  centrif- 
ugalize. A  very  short  time  is  sufficient  to  separate  a  clear  supernatant 
liquid,  from  the  tint  of  which  the  extent  of  the  haemolysis  can  be  deduced. 
Before  replacing  the  tubes  in  the  thermostat,  they  should,  of  course,  be  shaken 
up.  Small  test-tubes  of  about  8  mm.  internal  diameter  and  short  enough  to 
go  conveniently  into  the  centrifuge  cups  are  the  most  serviceable. 

X  For  exact  work  a  longer  time  is  recommended.  But  for  the  student  the 
time  is  made  as  short  as  possible,  and  it  is  only  in  exceptional  cases  that  ten 
minutes  is  not  enough. 


PRACTICAL  EXERCISES  73 

laking  in  either  G  or  H,  or  if  there  is  laking  it  may  be  greater  in  G  than 
in  li.  The  amboceptor  has  been  removed  from  serum  S  by  the  rabbit's 
corpuscles.  Add  o-i  c.c.  of  this  '  inactivated  '  serum  to  the  balance 
of  D,  D',  and  E,  E'  (left  from  6).  Laking  will  occur  because  the  serum  S 
contains  complement,  and  the  heated  serum  added  in  (6)  to  these  tubes 
contains  amboceptor.  Wash  the  rabbit's  corpuscles  which  have  been 
treated  with  ox  serum  at  0°  C.  with  cooled  sodium  chloride  solution. 
Add  to  them  some  of  serum  S  (that  from  the  top  of  tube  H  will  do  if 
no  more  is  left),  and  put  at  40°  C.  Laking  will  occur,  showing  that  the 
amboceptor  was  fixed  by  the  rabbit's  corpuscles  at  0°  C.  To  a  further 
portion  of  the  washed  rabbit's  corpuscles  which  were  treated  with  ox 
serum  at  0°  C.  add  normal  rabbit's  serum,  and  put  at  40°  C.  If  laking 
occurs  it  is  because  the  rabbit's  serum  contains  complement. 

Dog's  serum  may  be  used  instead  of  ox  serum  for  experiment  (8). 

16.  Osmotic  Resistance  of  the  Coloured  Corpuscles. — Fill  a  burette 
with  a  I  per  cent,  solution  of  sodium  chloride  and  another  with  dis- 
tilled water.  Take  a  series  of  ten  test-tubes  and  run  into  the  first 
6  c.c.  of  the  NaCl  solution,  into  the  second  5-8  c.c,  into  the  third 
5*6  c.c,  and  so  on,  always  making  a  difference  of  0-2  c.c  between 
successive  test-tubes.  From  the  other  burette  run  in  enough  distilled 
water  to  make  up  10  c.c.  of  solution  in  each  tube — that  is,  4  c.c.  of  dis- 
tilled-water  for  the  first  tube,  4-2  c.c.  for  the  second,  and  so  on.  Shake 
up.  The  tubes  now  contain  a  series  of  solutions  of  salt  differing  in 
strength  by  0-02  per  cent,  in  successive  tubes,  the  strongest  being  o-6 
per  cent.,  and  the  weakest  0-42  per  cent.  Number  the  tubes  i  to  10, 
beginning  with  the  strongest  solution.  Put  into  each  tube  one  drop  of 
perfectly  fresh  blood.  Shake  moderately  so  as  to  mix  the  blood  and 
salt  solution,  and  allow  the  tubes  to  stand  for  ten  to  thirty  minutes. 
Observe  the  colour  of  the  clear  liquid  above  the  sediment  of  corpuscles. 
Determine  in  which  tube  the  first  tinge  of  haemoglobin  appears.  The 
next  higher  concentration  of  the  salt  solution  is  that  in  which  all  the 
corpuscles  are  just  able  to  retain  their  haemoglobin,  and  is  a  measure  of 
the  minimum  osmotic  resistance  of  the  corpuscles,  or  the  resistance 
of  the  weakest  corpuscles.  Repeat  with  blood  which  has  stood  at  room 
temperature  for  twelve  to  twenty-four  hours.  For  clinical  purposes 
tubes,  each  containing  5  c.c.  of  salt  solution,  may  be  used.  A  single 
drop  of  blood  can  then  be  distributed  between  the  tubes  with  a  fine 
pipette  or  a  glass  rod,  beginning  with  the  most  concentrated  solution, 
and  passing  down  to  the  less  concentrated.  The  blood  must  be  dis- 
tributed rapidly  before  coagulation  occurs.  Only  such  concentrations 
of  the  salt  solution  as  are  known  to  correspond  to  the  possible  variations 
of  the  osmotic  resistance  for  any  particular  disease  or  for  any  particular 
variety  of  blood  need  be  employed. 

17.  Blood-Pigment — (i)  Preparation  of  Haemoglobin  Crystals. — (a) 
To  a  little  dog's  blood  in  a  narrow  test-tube  add  its  own  volume  or 
twice  its  volume  of  chloroform.  In\crt  the  tube  ten  or  twelve  times 
so  as  to  allow  the  chloroform  to  act  on  the  blood,  but  avoid  violent 
shaking.  When  the  tube  is  now  allowed  to  stand  for  a  few  minutes 
the  laked  blood  all  rises  to  the  top.  Remove  a  little  of  the  layer  of 
blood  without  taking  with  it  any  of  the  chloroform  layer,  and  examine 
the  oxyhaemoglobin  crystals  with  the  microscope.  They  form  long 
rhombic  prisms  and  needles  (Fig.  14,  p.  52). 

(6)  Add  a  little  crude  saponin  to  dog's  blood  in  a  test-tube.  Shake 
up  well,  and  allow  it  to  stand  till  the  colour  becomes  dark.  Then  shake 
vigorously,  and  a  mass  of  haemoglobin  crystals  will  be  formed. 

(c)  Put  a  small  drop  of  guinea-pig's  blood  on  a  slide.     .Mix  with  a 


74  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

drop   of    Canada   balsam   and    cover.     Tetrahedral    crystals    of    oxy- 
hasmoglobin  will  form  after  a  time.     The  slide  may  be  kept. 

(2)  Spectroscopic  Examination  of  Haemoglobin  and  its  Derivatives. 
— (a)  With  a  small,  direct-vision  spectroscope  look  at  a  bright  part  of 
the  sky  or  a  white  cloud.  Focus  by  pulling  out  or  pushing  in  the  eye- 
piece until  the  numerous  fine  dark  lines  (Fraunhofer's  lines),  running 
vertically  across  the  spectrum,  are  seen.  Narrow  the  slit  by  moving 
the  milled  edge  till  the  lines  are  as  sharp  as  they  can  be  made.  Note 
especially  the  line  D  in  the  orange,  the  lines  E  and  b  in  the  green, 
and  F  in  the  blue.  Always  hold  the  spectroscope  so  that  the  red  is 
at  the  left  of  the  field.  Now  dip  an  iron  or  platinum  wire  with  a 
loop  on  the  end  of  it  into  water,  and  then  into  some  common  salt  or 
sodium  carbonate,  and  fasten  or  hold  it  in  the  flame  of  a  fishtail  burner. 
On  examining  the  flame  with  the  spectroscope,  a  bright  yellow  line 
will  be  seen  occupying  the  position  of  the  dark  line  D  in  the  solar 
spectrum.  This  is  a  convenient  line  of  reference  in  the  spectrum,  and 
in  studying  the  spectra  of  haemoglobin  and  its  derivatives,  the  position 
of  the  absorption  bands  with  regard  to  the  D  line  should  always  be 
noted.  The  dark  lines  in  the  solar  spectrum  are  due  to  the  absorption 
of  light  of  a  definite  range  of  wave-lengths  by  metals  in  a  state  of  vapour 
in  the  sun's  atmosphere,  and  of  course  no  dark  lines  are  seen  in  the 
spectrum  of  a  gas-flame.     Put  some  defibrinated  blood  into  a  test-tube. 


B 

Fig.  20. — Direct  Vision  Spectroscope  ot  Simple  Type.  A ,  slot  in  which  a  pin  on  the 
eyepiece  C  slides  in  focussing  the  spectrum;  B,  milled  head,  by  the  rotation 
of  which  the  slit  is  narrowed  or  widened. 

Fasten  it  vertically  in  a  clamp  in  front  of  the  flame  and  examine  it 
with  the  spectroscope,  holding  the  latter  in  one  hand  with  the  slit  close 
to  the  test-tube,  and  focussing  the  eyepiece  with  the  other.  Or  arrange 
the  spectroscope,  test-tube  and  gas-flame  on  a  stand  as  in  Fig.  21. 
Nothing  can  be  seen  till  the  blood  is  diluted.  Pour  a  little  of  the  blood 
into  another  test-tube,  and  go  on  diluting  till,  on  focussing,  two  bands  oi 
oxyhcemoglobin  are  seen  in  the  position  indicated  in  Fig.  13,  p.  51.  Draw 
the  spectrum;  then  dilute  still  more,  and  observe  which  of  the  bands 
first  disappears.  Now  put  5  c.c.  of  the  blood  into  another  test-tube, 
and  dilute  it  with  four  times  its  volume  of  water.  Take  5  c.c.  of  this 
dilution,  and  again  add  four  times  as  much  water,  and  so  on  till  the 
solution  is  only  faintly  coloured.  Note  with  what  degree  of  dilution 
the  bands  disappear.  Then  examine  each  of  the  solutions  with  the 
spectroscope  and  draw  its  spectrum. 

[b)  Make  a  solution  of  blood  which  shows  the  oxyhsemoglobin  bands 
sharply.  Add  some  ammonium  sulphide  solution  to  reduce  the  oxy- 
hsemoglobin.  Heat  gently  to  about  body  temperature.  A  single, 
ill-defined  band  now  appears,  occupying  a  position  midway  between 
the  oxyhaemoglobin  bands,  and  the  latter  disappear.  This  is  the 
band  of  reduced  hcemoglobin  (Fig.  13). 

(c)  Carbonic  Oxide  Hcemoglobin. — Pass  coal-gas  through  blood   for 


PRACTICAL  EXERCISES 


75 


TesI'  tube 


Specfrosco/ie 
Sohilion 


a  considerable  time.  Examine  some  of  the  blood  (after  dilution) 
with  the  spectroscope.  Two  bands,  almost  in  the  position  of  the 
oxy'haemoglobin  bands,  are  seen;  but  no  change  is  caused  by  the 
addition  of  ammonium  sulphide,  since  carbonic  oxide  haemoglobin  is 
a  more  stable  compound  than  oxy haemoglobin. 

{d)  Methcsmoglobin. — Put  some  blood  into  a  test-tube,  add  a  few 
drops  of  a  solution  of  ferricyanidc  of  potassium,  and  heat  gently.  On 
diluting  a  well-marked  band  will  be  seen  in  the  red.  On  addition  of 
ammonium  sulphide  this  band  disappears;  the  oxyhaeraoglobin  bands 
are  seen  for  a  moment,  and  then  give  place  to  the  band  of  reduced 
haemoglobin  (Fig.  13,  p.  51). 

{$)  Acid  Ha;matin. — To  a  little  diluted  blood  add  strong  acetic  acid 
and  heat  gently.  The  colour  becomes  brownish.  The  spectrum 
shows  a  band  in  the  red  between  C  and  D,  not  far  from  the  position 
of  the  band  of  methaemoglobin.  The  addition  of  a  drop  or  two  of 
ammonium  sulphide  causes  no  change  in  the  spectrum,  and  this  is  a 
means  of  distinguishing  acid  hasmatin  from  methaemoglobin.  If  more 
ammonium  sulphide  be  added,  _ 

haematin  will  be  precipitated 
when  the  acid  solution  has  been 
rendered  neutral,  and  a  further 
addition  of  ammonium  sulphide 
or  sodium  hydroxide  will  cause 
the  haematin  to  be  again  dis- 
solved, a  solution  of  alkaline 
haematin  being  formed.  This 
in  its  turn  may  be  reduced  by 
an  excess  of  ammonium  sul- 
phide, and  the  spectrum  of 
haemochromogen  may  be  ob- 
tained (Fig.  13,  p.  51). 

Since  the  watery  solution 
of  acid  haematin  obtained  as 
above  is  usually  somewhat  tur- 
bid, a  solution  in  acid  ether  is 
sometimes  employed  for  spec- 
troscopic examination.  Add  to 
a  little  undiluted  defibrinated 
blood  about  half  its  volume  of 
glacial  acetic  acid,  and  then  not 
less  than  an  equal  volume  of 

ether.  Mix  well,  pour  off  the  ethereal  extract  and  examine  it  with  the 
spectroscope,  diluting,  if  necessary,  with  ether  and  glacial  acetic  acid. 
It  shows  a  strong  band  in  the  red  somewhat  farther  from  the  D  line 
than  the  methaemoglobin  band.  On  dilution,  thr.':,'  additional  fainter 
bands  may  be  seen. 

(/)  Alkaline  HcBmatin. — To  diluted  blood  add  strong  acetic  acid  and 
warm  gently  for  a  few  minutes.  Then,  when  the  spectroscopic  ex- 
amination of  a  sample  shows  that  acid  haematin  has  been  formed, 
neutralize  with  sodium  hydroxide.  A  brownish  precipitate  of  haematin 
is  thrown  down,  which  dissolves  in  an  excess  of  sodium  hydroxide, 
giving  a  solution  of  alkaline  haematin  (or  alkali  haematin). 

Or  add  sodium  hydroxide  to  blood  directly,  and  warm  for  a  couple  of 
minutes  after  the  colour  has  changed  decidedly  to  brownish-black. 
The  spectrum  of  alkaline  haematin  is  a  broad  but  ill-defined  band  just 
overlapping  the  D  line,  and  situated  chiefly  to  the  red  side  of  it  (Fig.  13). 
The  solution  should  be  shaken  up  with  air  before  being  examined,  as 


Fig.  21. 


-Spectroscopic  Examination  of 
Blood-Pigment. 


76  THE  CIRCULATING  LIQUIDS  OF  THE  BODY 

some  of  the  alkali  haematin  is  changed  into  haemochromogen  by  re- 
ducing substances  formed  by  the  action  of  the  alkali  on  the  blood. 

(g)  HcBmochromogen. — To  a  solution  of  alkaline  haematin  add  a  drop 
or  two  of  ammonium  sulphide.  The  band  near  D  disappears,  and  two 
bands  make  their  appearance  in  the  green  (Fig.  13,  p.  51). 

(A)  H amatoporphyrin . — Put  some  strong  sulphuric  acid  into  a  test- 
tube.  Add  a  few  drops  of  blood,  agitate  the  test-tube  till  the  blood 
dissolves,  and  examine  the  purple  liquid,  diluting  it,  if  necessary, 
with  sulphuric  acid.  Its  spectrum  shows  two  well-marked  bands,  one 
just  to  the  left  of  D,  and  the  other  midway  between  D  and  E  (Fig.  13). 

(3)  Guaiacum  Test  for  Blood. — A  test  for  blood — much  used  in 
hospitals,  and,  indeed,  a  delicate  one,  but  quite  untrustworthy  unless 
certain  precautions  be  taken — is  the  guaiacum  test.  A  drop  of  freshly- 
prepared  tincture  of  guaiacum  is  added  to  the  liquid  to  be  tested,  and 
then  peroxide  of  hydrogen.  If  blood  be  present,  the  guaiacum  strikes 
a  blue  or  greenish-blue  colour.  The  decomposition  of  the  peroxide 
by  the  blood  is  due  mainly  to  the  haemoglobin  of  the  corpuscles.  Any 
derivative  of  haemoglobin  which  still  contains  the  iron  will  act,  and 
boiling  does  not  abolish  this  power.  On  the  other  hand,  oxydases  or 
oxidizing  ferments  present,  not  only  in  the  formed  elements  of  blood, 
but  elsewhere,  e.g.,  in  fresh  vegetable  protoplasm,  milk,  seminal  fluid, 
and  pus,  will  cause  the  same  colour  (p.  267),  but  not  if  they  have  been 
previously  boiled.*  The  test  has  been  considered  chiefly  of  value  as 
a  negative  test.  When  the  blue  colour  is  not  obtained,  we  have  good 
evidence  that  blood  is  absent.  But,  according  to  Buckmaster,  if  the 
precaution  of  first  boiling  the  liquid  suspected  to  contain  blood  be 
adopted,  it  is  also  a  good  positive  test.  It  is,  however,  far  inferior  to 
the  haemin  test  (p.  78)  where  that  can  be  obtained,  and  of  course  in- 
ferior to  the  identification  of  erythrocytes  with  the  microscope,  or  to 
the  spectroscopic  identification  of  the  blood-pigment  where  the  material 
is  suitable  for  this. 

(4)  Quantitative  Estimation  of  Haemoglobin — (a)  By  Haldane's  Modi- 
fication of  Corners'  Hcemoglobinonieter. — Place  in  the  graduated  tube  B 
(Fig.  22)  an  amount  of  water  less  than  will  ultimately  be  required  to 
dilute  the  blood  to  the  required  tint.  Puncture  the  finger  or  lobe  of 
the  ear  with  one  of  the  small  lancets  in  F,  and  fill  the  capillary  pipette  D 
to  a  little  beyond  the  mark  20.  Wipe  the  point  of  the  pipette  and  dab 
it  on  a  piece  of  filter-paper  till  the  blood  stands  exactly  at  the  mark. 
Blow  the  blood  into  the  water  in  B,  and  rinse  the  pipette  with  the  water. 
Attach  the  cap  of  tube  G  to  a  gas-burner.  Introduce  the  rubber  tube 
into  B  nearly  to  the  level  of  the  water,  and  allow  gas  to  pass  for  a  few 
seconds.  Withdraw  the  tube  while  the  gas  is  still  passing.  Immediately 
close  the  end  of  B  with  the  finger,  and  move  the  tube  so  that  the 
liquid  passes  from  end  to  end  of  it  at  least  a  dozen  times,  to  saturate 
the  haemoglobin  with  carbonic  oxide.  While  this  is  being  done,  the 
tube  should  be  held  in  a  cloth,  otherwise  it  will  become  heated,  and 
liquid  will  spurt  out  when  the  finger  is  removed.     Water  is  now  added 

*  The  formed  elements  of  blood  really  contain  no  less  than  three  ferments 
of  interest  in  this  connection:  (i)  A  catalase  which  decomposes  peroxide  of 
hydrogen  into  water  and  molecular  oxygen  {i.e.,  oxygen  not  in  the  atomic 
or  nascent  state).  This  reaction  is  given  by  both  blood  and  pus.  (2)  An 
oxydase  (also  spelled  oxidase),  which  oxidizes  guaiacum  and  similar  substances 
without  the  presence  of  hydrogen  peroxide.  This  reaction  is  obtainable  even 
from  aqueous  extracts  of  leucocytes.  (3)  A  peroxydase  (also  spelled  peroxi- 
dase) which  causes  the  oxidation  of  these  substances  only  in  the  presence  of 
hydrogen  peroxide,  a  reaction  also  given  by  leucocytes.  These  ferments  are 
all  inactivated  iby  boiling  (Kastle). 


PRACTICAL  EXERCISES 


r, 


drop  by  drop  with  the  pipette  stopper  of  the  bottle  E,  which  is  used 
for  holding  the  water,  the  tube  being  inverted  after  each  addition, 
till  the  tint  in  B  is  the  same  as  that  in  A.  In  comparing  the  tubes, 
they  should  be  held  against  the  light  from  the  sky  or  from  an  opal 
glass  lamp-shade.  It  is  necessary  to  transpose  the  tubes  repeatedly. 
The  level  at  which  the  tints  are  equal  is  read  off  on  B  half  a  minute 
after  the  addition  of  the  last  drop  of  water.  Water  is  now  again  added 
by  drops  till  the  tint  in  B  is  just  mticeably  weaker  than  in  A,  and  the 
mean  of  the  two  readings  is  taken.  The  result  is  the  percentage  actually 
present  of  the  average  proportion  of  haemoglobin  in  the  blood  of  healthy 
adult  males.  Healthy  women  give  an  average  of  only  89  per  cent., 
and  healthy  children  an  average  of  only  87  per  cent.,  of  the  proportion 
in  men.  The  liquid  in  A  is  a  i  per  cent,  solution  of  blood  containing 
the  average  percentage  of  hcemoglobin  found  in  the  blood  of  healthy 


Fig.  22. — Haldane's  Modification  of  Gowers'  Haemoglobinometer. 


adult  males,  and  having  an  oxygen  capacity  of  18  3  per  cent. — i.e., 
100  c.c.  of  the  blood  with  which  the  standard  was  made  would  take 
up  in  combination  from  air  i8;5  c.c.  of  oxygen.  The  solution  in  A  has 
been  saturated  with  carbonic  oxide. 

This  method  is  probably  more  accurate  than  any  other  used  in  clinical 
work,  the  error,  in  the  hands  of  an  experienced  observer,  not  exceeding 
I  per  cent. 

(b)  By  Fleischl's  Hcemometer  (Fig.  23). — Fill  with  distilled  water  that 
compartment  a'  of  the  small  cylinder  (above  the  stage)  wjiich  is  over 
the  tinted  wedge.  Put  a  little  distilled  water  into  the  other  compart- 
ment a.  Now  prick  the  finger  and  fill  one  of  the  small  capillary  tubes 
with  blood.  See  that  none  of  the  blood  is  smeared  on  the  out.'^ide  of 
the  tube.  Then  wash  all  the  blood  into  the  water  in  compartment  a. 
and  fill  it  to  the  brim  with  distilled  water.     By  means  of  the  milled 


78 


THE  CIRCULATING  LIQUIDS  OF  THE  BODY 


head  T  move  the  tinted  wedge  K  till  the  depth  of  colour  is  the  same 
in  the  two  compartments.  The  percentage  of  the  normal  quantity 
of  haemoglobin  is  given  by  the  graduated  scale  P.  For  example,  if  the 
reading  is  90,  the  blood  contains  90  per  cent,  of  the  normal  amount; 
if  100,  it  contains  the  normal  quantity.  The  observations  should  be 
made  in  a  dark  room,  the  white  surface  S,  arranged  below  the  compart- 
ments a  and  a',  being  illuminated  by  a  lamp.  Or  the  instrument  may 
be  placed  in  a  small  box,  lighted  by  a  candle.  It  is  best  that  each  result 
should  be  the  mean  of  two  readings,  one  just  too  large  and  the  other 
just  too  small.  In  any  case  the  instrument  does  not  give  readings 
accurate  to  less  than  5  per  cent. 

(c)  Hoppe-Seyler's  Method. — Two  parallel-sided  glass  troughs  are 
used.  In  one  is  put  a  standard  solution  of  oxyhaemoglobin  of  known 
strength,    in    the   other    a    measured    quantity    of    the    blood   to    be 

tested.   The  latter  is  diluted 
'"^        /  „  with   water  until   its   tint 

appears  the  same  as  that 
of  the  standard  solution, 
when  the  troughs  are  placed 


Fig.  23. — Fleischl'b  Haeniometer. 


Crystals  of  Haemin 
(Frey). 

side  by  side  on  white  paper. 
From  the  quantity  of  water 
added  it  is  easy  to  calculate 
the  proportion  of  haemo- 
globin in  the  undiluted 
blood.  Greater  accuracy  is  obtained  if  the  haemoglobin  in  the  standard 
solution  and  that  of  the  blood  are  converted  into  carbonic  oxide  haemo- 
globin by  passing  a  stream  of  coal-gas  through  them. 

(d)  Tallquist's  Method. — In  this  method  the  tint  produced  by  a 
drop  of  blood  on  a  piece  of  white  filter-paper  is  compared  with  a  scale 
representing  10  percentages  of  haemoglobin  (from  10  to  100  per  cent.). 
The  standard  filter-paper  is  supplied  in  the  form  of  a  book  with  the 
scale.  To  make  an  estimation,  all  that  is  necessary  is  to  touch  a  drop 
of  blood  with  a  piece  of  the  filter-paper,  and  allow  the  blood  to  diffuse 
slowly  through  the  paper,  so  as  to  give  an  even  stain.  The  position 
of  the  stain  is  then  determined  by  the  scale;  e.g.,  it  may  be  deeper 
than  90,  but  fainter  than  100,  in  which  case  the  percentage  of  haemo- 
globin lies  between  90  and  100.  The  method  is  by  no  means  a  very 
acciirateonc,  but  more  accurate  than  it  appears  at  first  sight. 

(5)  Microscopic  Test  for  Blood-Pigment. — Put  a  drop  of  blood  on  a 
slide.  Allow  the  blood  to  dry,  or  heat  it  gently  over  a  flame,  so  as  to 
evaporate  the  water.     Add  a  drop  of  glacial  acetic  acid ;  put  on  a  co\  er- 


PRACTICAL  EXERCISES  79 

glass,  and  again  heat  slowly  till  the  liquid  just  begins  to  boil.  Take 
the  slide  away  from  the  flame  for  a  few  seconds,  then  heat  it  again  for 
a  moment;  and  repeat  this  process  two  or  three  times.  Now  let  the 
slide  cool,  and  examine  with  the  microscope  (high  power).  The  small 
black,  or  brownish-black,  cr^'stals  of  ha;min  will  be  seen  (Fig.  24,  p.  78). 
This  is  an  important  test  where  only  a  minute  trace  of  blood  is  to  be 
examined,  as  in  some  medico-legal  cases.  If  a  blood-stain  is  old,  a 
minute  crystal  of  sodium  chloride  should  be  added  along  w^ith  the 
glacial  acetic  acid.     Fresh  blood  contains  enough  sodium  chloride. 

A  blood-stain  on  a  piece  of  cloth  may  first  of  all  be  soaked  in  a  small 
quantity  of  distilled  water,  and  the  liquid  examined  with  the  spectro- 
scope or  the  micro-spectroscope  (a  microscope  in  which  a  small  spectro- 
scope is  substituted  for  the  eyepiece).  Then  evaporate  the  liquid  to 
dryness  on  a  water-bath,  and  apply  the  haemin  test.  Or  perform  the 
hsemin  test  directly  on  the  piece  of  cloth.  In  a  fresh  stain  the  blood- 
corpuscles  might  be  recognized  under  the  microscope.  Very  few 
liquids,  however,  are  available  for  washing  out  the  blood,  as  all  ordinary 
solutions,  and  even  serum  itself,  cause  laking  of  dried  corpuscles 
(Guthrie).  Absolute  alcohol,  or  35  per  cent,  potassium  hydroxide, 
may  be  used  to  soak  and  rub  up  the  cloth  in. 


CHAPTER  III 

THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

The  blood  can  only  fulfil  its  functions  by  continual  movement. 
This  movement  implies  a  constant  transformation  of  energy;  and  in 
the  animal  body  the  transformation  of  energy  into  mechanical  work 
is  almost  entirely  allotted  to  a  special  form  of  tissue,  muscle.  In 
most  animals  there  exist  one  or  more  rhythmically  contractile 
muscular  organs,  or  hearts,  upon  which  the  chief  share  of  the  work 
of  keeping  up  the  circulation  falls. 

Section  I. — Preliminary  Anatomical  and  Physical  Data. 

Comparative. — In  Echinus  a  contractile  tube  connects  the  two  vascu- 
lar rings  that  surround  the  beginning  and  end  of  the  alimentary  canal, 
and  plays  the  part  of  a  heart.  In  the  lower  Crustacea  and  in  insects 
the  heart  is  simply  the  contractile  and  generally  sacculated  dorsal 
bloodvessel;  in  the  higher  Crustacea,  such  as  the  lobster,  it  is  a  well- 
defined  muscular  sac  situated  dorsally.  A  closed  vascular  system  is 
the  exception  among  invertebrates.  In  most  of  them  the  blood 
passes  from  the  arteries  into  irregular  spaces  or  lacunae  in  the  tissues, 
and  thence  finds  its  way  back  to  the  heart.  In  the  primitive  vertebrate 
heart  five  parts  can  be  distinguished  as  we  proceed  from  the  venous 
to  the  arterial  end:  (i)  The  sinus  venosus,  into  which  the  great  veins 
open;  (2)  the  auricular  canal,  from  the  dorsal  wall  of  which  is  developed 
— (3)  the  auricle;  (4)  the  ventricle;  (5)  the  bulbus  arteriosus,  from  which 
the  chief  artery  starts  (Fig.  25,  p.  81).  Amphioxus,  the  lowest  verte- 
brate, has  a  primitive  lacunar  vascular  system;  a  contractile  dorsal 
bloodvessel  serves  as  arterial  or  systemic  heart,  a  contractile  ventral 
vessel  as  venous  or  respiratory  heart.  From  the  latter,  vessels  go  to 
the  gills.  Fishes  possess  only  a  respiratory  heart,  consisting  of  a  venous 
sinus,  auricle,  ventricle,  and  bulbus  arteriosus.  This  drives  the  blood 
to  the  gills,  from  which  it  is  gathered  into  the  aorta;  it  has  thence  to 
find  its  way  without  further  propulsion  through  the  systemic  vessels. 
Amphibians  have  a  venous  sinus,  two  auricles,  a  single  "'e^itricle,  and 
an  arterial  bulb;  reptiles,  two  auricles  and  two  incompletely-separated 
ventricles.  In  birds  and  mammals  the  respiratory  and  systemic 
hearts  are  completely  separated.  The  former,  consisting  of  the  right 
auricle  and  ventricle,  propels  the  blood  through  the  lungs;  the  latter, 
consisting  of  the  left  auricle  and  ventricle,  receives  it  from  the  pul- 
monary veins,  and  sends  it  through  the  systemic  vessels. 

The  sinus  venosus  seems  to  be  represented  in  the  mammalian  heart 
by  certain  small  portions  of  tissue,  especially  the  so-called  sino-auricular 
node,  a  little  knot  of  primitive  fibres  near  the  mouth  of  the  superior 

80 


ANATOMICAL  AND  PHYSICAL  DATA 


8i 


vena  cava.  The  auricular  canal  is  probably  represented  by  the 
auriculo-ventricular  bundle  (conveniently  designated  as  the  a. -v.  bundle), 
which  will  again  be  referred  to  in  relation  to  the  conduction  of  the  heart- 
beat from  auricles  to  ventricles  (p.  147).  This  bundle  starts  from  a 
clump  of  primitive  tissue,  the  auriculo-ventricular  node  (a. -v.  node) 
at  the  base  of  the  interauricular  septum  on  the  right  side,  below  and 
to  the  right  of  the  coronary  sinus,  and  runs  down  the  interventricular 
septum.  The  sino-auricular  and  the  auriculo-ventricular  nodes  are 
connected  by  fibres  which  run  in  the  interauricular  septum,  so  that  it 
may  be  considered  that  the  primitiv-e  cardiac  tube  is  still  represented 
from  base  to  apex  of  the  adult 
mammalian  heart,  although  only 
by  very  slender  threads  of  tissue, 
amidst  the  massive  secondary' 
developments  of  auricular  and 
ventricular  muscle  (Keith  and 
Flack) . 

General  View  of  the  Circulation 
in  Man. — The  whole  circuit  of  the 
blood  is  divided  into  two  portions, 
very  distinct  from  each  other, 
both  anatomically  and  function- 
ally— the  respirator^'  or  lesser 
circulation,  and  the  systemic  or 
greater  circulation.  Starting  from 
the  left  ventricle,  the  blood  passes 
along  the  systemic  vessels — ar- 
teries, capillaries,  veins — and,  on 
returning  to  the  heart,  is  poured 
into  the  right  auricle,  and  thence 
into  the  right  ventricle.  From 
the  latter  it  is  driven  through  the 
pulmonary  artery  to  the  lungs, 
passes  through  the  capillaries  of 
these  organs,  and  returns  through 
the  pulmonary  veins  to  the  left 
auricle  and  ventricle.  The  portal 
system,  which  gathers  up  the 
blood  from  the  intestines,  forms 
a  kind  of  loop  on  the  systemic 
circulation.  The  lymph-current 
is  also  in  a  sense  a  slow  and  stag- 
nant side-stream  of  the  blood- 
circulation  ;  for  substances  are 
constantly     passing     from     the 

bloodvessels  into  the  lymph -spaces,  and  returning,  although  after  a  com- 
paratively long  interval,  into  the  blood  by  the  great  lymphatic  trunks. 

Physiological  Anatomy  of  the  Vascular  System. — The  heart  is  to  be 
looked  upon  as  a  portion  of  a  bloodvessel  which  has  been  modified  to 
act  as  a  pump  for  driving  the  blood  in  a  definite  direction.  Morpho- 
logically it  is  a  bloodvessel;  and  the  physiological  propert>^  of  auto- 
matic rhythmical  contraction  which  belongs  to  the  heart  in  so  eminent 
a  degree  is,  as  has  been  mentioned  (p.  80),  an  endowment  of  blood- 
vessels in  many  animals  that  possess  no  localized  heart.  Even  in 
some  mammals  contractile  bloodvessels  occur;  the  veins  of  the  bat's 
wing,  for  example,  beat  with  a  regular  rhythm,  and  perform  the  func- 
tion of  accessor/  hearts. 

6 


Fig.  25. — Diagram  of  Primitive  Vertebrate 
Heart,  combining  Features  found  in  the 
Eel.  Dogfish,  and  Frog  (Flack,  after 
Keith),  a.  Sinus  venosus;  b.  auricular 
canal;  c,  auricle;  d,  ventricle;  e.  bulbus 
cordis;  /,  aorta;  i-i.  sino-auricular  junc- 
tion and  venous  valves;  2-2,  junction  of 
canal  and  auricle;  3-3.  annular  part  of 
auricle;  5,  bulbo-ventricular  junction. 


82  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

The  whole  vascular  system  is  lined  with  a  single  layer  of  endothelial 
cells.  In  the  capillaries  nothing  else  is  present;  the  endothelial  layer 
forms  the  whole  thickness  of  the  wall.  In  young  animals,  at  any  rate, 
the  endothelial  cells  of  the  capillaries  are  capable  of  contracting  when 
stimulated;  and  changes  in  the  calibre  of  these  vessels  can  be  brought 
about  in  this  way.  The  walls  of  the  arteries  and  veins  are  chiefly 
made  up  of  two  kinds  of  tissue,  which  render  them  distensible  and 
f  elastic:  non-striped  muscular  fibres  and  yellow  elastic  fibres.  The 
muscular  fibres  are  mainly  arranged  as  a  circular  middle  coat,  which, 
especially  in  the  smaller  arteries,  is  relatively  thick.  One  conspicuous 
layer  of  elastic  fibres  marks  the  boundary  between  the  middle  and 
inner  coats.  In  the  larger  arteries  elastic  laminae  are  also  scattered 
freely  among  the  muscular  fibres  of  the  middle  coat.  The  outer  coat 
is  composed  chiefly  of  ordinary  connective  tissue.  The  veins  differ 
from  the  arteries  in  having  thinner  walls,  with  the  layers  less  distinctly 
marked,  and  containing  a  smaller  proportion  of  non-striped  muscle 
and  elastic  tissue ;  although  in  some  veins,  those  of  the  pregnant  uterus, 
for  instance,  and  the  cardiac  ends  of  the  large  thoracic  veins,  there  is 
a  greater  development  of  muscular  tissue.  Further,  and  this  is  of  prime 
physiological  importance,  valves  are  present  in  many  veins.  These 
are  semilunar  folds  of  the  internal  coat  projecting  into  the  lumen  in 
such  a  direction  as  to  favour  the  flow  of  blood  towards  the  heart, 
but  to  check  its  return.  In  some  veins,  as  the  venae  cavae,  the  pulmonary 
veins,  the  veins  of  most  internal  organs,  and  of  bone,  there  are  no  valves ; 
in  the  portal  system  they  are  rudimentary  in  man  and  the  great  majority 
/  of  mammals.  The  valves  are  especially  well  marked  in  the  lower  limbs, 
1  where  the  venous  circulation  is  uphill.  When  a  valve  ceases  to  perform 
•  its  function  of  supporting  the  column  of  blood  between  it  and  the 
valve  next  above,  the  foundation  of  varicose  veins  is  laid;  the  valve 
immediately  below  the  incompetent  one,  having  to  bear  up  too  great 
a  weight  of  blood,  tends  to  yield  in  its  turn,  and  so  the  condition  spreads. 
The  smallest  veins,  or  venules,  are  very  like  the  smallest  arteries,  or 
arterioles,  but  somewhat  wider  and  less  muscular.  The  transition 
from  the  capillaries  to  the  arterioles  and  venules  is  not  abrupt,  but 
may  be  considered  as  marked  by  the  appearance  of  the  non-striped 
muscular  fibres,  at  first  scattered  singly,  but  gradually  becoming  closer 
and  more  numerous  as  we  pass  away  from  the  capillaries,  until  at  length 
they  form  a  complete  layer. 

In  the  heart  the  muscular  element  is  greatly  developed  and  differ- 
entiated. Both  histologically  and  physiologically  the  fibres  seem  to 
stand  between  the  striated  skeletal  muscle  and  the  smooth  muscle.  In 
the  mammal  the  cardiac  muscular  fibres  are  generally  described  as 
made  up  of  short  oblong  cells,  devoid  of  a  sarcolemma,  often  branched, 
and  arranged  in  anastomosing  rows,  each  cell  having  a  single  nucleus 
in  the  middle  of  it.  But  it  has  recently  been  shown  that  the  muscle 
fibrils  run  right  through  the  apparent  cell  boundaries,  and  form  a  con- 
tinuous sheet  of  tissue  anastomosing  in  every  direction.  The  fibres 
are  transversely  striated,  but  the  striae  are  not  so  distinct  as  in  skeletal 
muscle.  A  sarcolemma  is  not  absent,  although  it  is  more  delicate 
than  in  skeletal  muscle,  and  perhaps  of  a  different  nature.  Many 
fibres  pass  from  one  auricle  to  the  other,  and  from  one  ventricle  to  the 
other. 

In  the  frog's  heart  the  muscular  fibres  are  spindle-shaped,  like  those 
of  smooth  muscle,  but  transversely  striated,  like  those  of  skeletal 
muscle.  From  the  sinus  to  the  apex  of  the  ventricle  there  is  a  con- 
tinuous sheet  of  muscular  tissue. 


ANATOMICAL  AND  PHYSICAL  DATA  83 

The  problems  of  the  circulation  are  partly  physical,  partly  vital. 
Some  of  the  phenomena  observed  in  the  blood-stream  of  a  living 
animal  can  be  reproduced  on  an  artificial  model ;  and  they  may  justly 
be  called  the  physical  or  mechanical  phenomena  of  the  circulation. 
Others  are  essentially  bound  up  with  the  properties  of  living  tissues; 
and  these  may  be  classified  as  the  vital  or  physiological  phenomena  of 
the  circulation.  The  distinction,  although  by  no  means  sharp  and 
absolute,  is  a  convenient  one — at  least,  for  purposes  of  description; 
and  as  such  we  shall  use  it.  But  it  must  not  be  forgotten  that  the 
physiological  factors  play  into  the  sphere  of  the  physical,  and  the 
physical  factors  modify  the  physiological.  Considered  in  its 
physical  relations,  the  circulation  of  the  blood  is  the  flow  of  a  liquid 
along  a  system  of  elastic  tubes,  the  bloodvessels,  under  the  influence 
of  an  intermittent  pressure  produced  by  the  action  of  a  central 
pump,  the  heart.  But  the  branch  of  dynamics  which  treats  of  the 
movement  of  hquids,  or  hydrodynamics,  is  one  of  the  most  difficult 
parts  of  physics,  and  even  in  the  physical  portion  of  our  subject  we 
are  forced  to  rely  chiefly  on  empirical  methods.  It  would,  therefore, 
not  be  profitable  to  enter  here  into  mathematical  theory,  but  it  may 
be  well  to  recall  to  the  mind  of  the  reader  one  or  two  of  the  simplest 
data  connected  with  the  flow  of  liquids  through  tubes: 

Torricelli's  Theorem. — Suppose  a  vessel  filled  with  water,  the  level 
of  which  is  kept  constant;  the  velocity  with  which  the  water  will 
escape  from  a  hole  in  the  side  of  the  vessel  at  a  vertical  depth  h  below 
the  surface  will  he  v=  >j2gh,  where  g  is  the  acceleration  produced  by 
gravity.*  In  other  words,  the  velocity  is  that  which  the  water  would 
have  acquired  in  falling  in  vacuo  through  the  distance  h.  This  formula 
was  deduced  experimentally  by  Torricelli,  and  holds  only  when  the 
resistance  to  the  outflow  is  so  small  as  to  be  negligible.  The  reason  of 
this  restriction  will  be  easily  seen,  if  we  consider  that  when  a  mass 
m  of  water  has  flowed  out  of  the  opening,  and  an  equal  mass  m  has 
flowed  in  at  the  top  to  maintain  the  old  level,  everything  is  the  same 
as  before,  except  that  energy  of  position  equal  to  that  possessed  by 
a  mass  w  at  a  height  h  has  disappeared.  If  this  has  all  been  changed 
into  kinetic  energy  E,  in  the  form  of  visible  motion  of  the  escaping 
water,  then  lE.  =  \mv^=mgh,  i.e.,  v=  \^2gh.  If,  however,  there  has  been 
any  sensible  resistance  to  the  outflow,  any  sensible  friction,  some  of 
the  potential  energy  (energ)^  of  position)  will  have  been  spent  in  over- 
coming this,  and  will  have  ultimately  been  transformed  into  the  kinetic 
energy  of  molecular  motion,  or  heat. 

Flow  of  a  Liquid  through  Tubes. — Next  let  a  horizontal  tube  of  uni- 
form cross-section  be  fitted  on  to  the  orifice.  The  velocity  of  outflow 
will  be  diminished,  for  resistances  now  come  into  play.  WhcMi  the 
liquid  flowing  through  a  tube  wets  it,  the  layer  next  the  wall  of  the 
tube  is  prevented  by  adhesion  from  moving  on.  The  particles  next 
this  stationary  layer  rub  on  it,  so  to  speak,  and  are  retarded,  although 
not  stopped  altogether.  The  next  layer  rubs  on  the  comparatively 
slowly  moving  particles  outside  it,  and  is  also  delayed,  althougli  not 
so  much  as  that  in  contact  with  the  immovable  layer  on  the  walls  of 

*  I.e..  the  amount  adtled  per  second  to  the  velocity  of  a  faUing  body 
(g'-=32feet). 


84 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


the  tube.  In  this  way  it  comes  about  that  every  particle  of  the  liquid 
is  hindered  by  its  friction  against  others — those  in  the  axis  of  the  tube 
least,  those  near  the  periphery  most — and  part  of  the  energy  of  position 
of  the  water  in  the  reservoir  is  used  up  in  overcoming  this  resistance, 
only  the  remainder  being  transformed  into  the  visible  kinetic  energy 
of  the  liquid  escaping  from  the  open  end  of  the  tube. 

If  vertical  tubes  be  inserted  at  different  points  of  the  horizontal 
tube,  it  will  be  found  that  the  water  stands  at  continually  decreasing 
heights  as  we  pass  away  from  the  reservoir  towards  the  open  end  of 
the  tube.  The  height  of  the  liquid  in  any  of  the  vertical  tubes  indicates 
the  lateral  pressure  at  the  point  at  which  it  is  inserted;  in  other  words, 
the  excess  of  potential  energy,  or  energy  of  position,  which  at  that 
point  the  liquid  possesses  as  compared  with  the  water  at  the  free  end, 
where  the  pressure  is  zero.  If  the  centre  of  the  cross-section  of  the 
free  end  of  the  tube  be  joined  to  the  centres  of  all  the  menisci,  it  will 
be  found  that  the  line  is  a  straight  line.  The  lateral  pressure  at  any 
point  of  the  tube  is  therefore  proportional  to  its  distance  from  the  free 
end.  Since  the  same  quantity  of  water  must  pass  through  each  cross- 
section  of  the  horizontal  tube  in  a  given  time  as  flows  out  at  the  open 
end,  the  kinetic  energy  of  the  liquid  at  every  cross-section  must  be 

constant  and  equal  to  hmv^, 
where  v  is  the  mean  velocity 
(the  quantity  which  escapes  in 
unit  of  time  divided  by  the 
cross-section)  of  the  water  at 
the  free  end. 

Just  inside  the  orifice  the 
total  energy  of  a  mass  m  of 
water  is  tngh;  just  beyond  it 
at  the  first  vertical  tube,  mgh' 
+  lmv^,  where  h'  is  the  lateral 
pressure.  On  the  assumption 
that  between  the  inside  of  the 
orifice  and  the  first  tube  no 
energy  has  been  transformed 
into  heat  (an  assumption 
the  more  nearly  correct  the 
smaller  the  distance  between 
it  and  the  inside  of  the  orifice  is  made),  we  have  mgh  =  mgh'  +  lmv^, 
i.e.,  lmv-^mg{h-h').  In  other  words,  the  portion  of  the  energy  of 
position  of  the  water  in  the  reservoir  which  is  transformed  into  the 
kinetic  energ}^  of  the  water  flowing  along  the  horizontal  tube  is  measured 
by  the  difference  between  the  height  of  the  level  of  the  reservoir  and 
the  lateral  pressure  at  the  beginning  of  the  horizontal  tube — that  is, 
the  height  at  which  the  straight  line  joining  the  menisci  of  the  vertical 
tubes  intersects  the  column  of  water  in  the  reservoir.  Let  H  represent 
the  height  corresponding  to  that  part  of  the  energy  of  position  which 
is  transformed  into  the  kinetic  energy  of  the  flowing  water.  H  is  easily 
calculated  when  the  mean  velocity  of  efflux  is  known.  For  v^  x/2gH 
by  Torricelli's  theorem  (since  none  of  t]ie  energy  corresponding  to  H 


Fig.  26. — Diagram  to  illustrate  Flow  of 
Water  along  a  Horizontal  Tube  connected 
with  a  Reservoir. 


is  supposed  to  be  used  up  in  overcoming  friction),  or  H 


^g 


At  the 


second  tube  the  lateral  pressure  is  only  h".  The  sum  of  the  visible 
kinetic  and  potential  energy  here  is  therefore  \mv''  +  mgh".  A  quantity 
of  energy  mg{h'  ~  h")  must  have  been  transformed  into  heat  owing  to 
the  resistance  caused   by  fluid  friction  in  the  portion  of  the  horizontal 


ANATOMICAL  AND  PHYSICAL  DATA  85 

tube  between  the  first  two  vertical  tubes.  In  general  the  energy  of 
position  represented  by  the  lateral  pressure  at  any  point  is  equal  to 
the  energy  used  up  in  overcoming  the  resistance  of  the  portion  of  the 
path  beyond  this  point. 

Velocity  of  Outflow. — It  has  been  found  by  experiment  that  v,  the 
mean  velocity  of  outflow,  when  the  tube  is  not  of  very  small  calibre, 
varies  directly  as  the  diameter,  and  therefore  the  volume  of  outflow 
as  the  cube  of  the  diameter.  In  fine  capillary  tubes  the  mean  velocity 
is  proportional  to  the  square,  and  the  volume  of  outflow  to  the  fourtli 
power  of  the  diameter  (Poiseuille).  If,  for  example,  the  linear  velocity 
of  the  blood  in  a  capillary  of  10  /x  in  diameter  is  h  mm.  per  sec,  it  will 
be  four  times  as  great  (or  2  mm.  per  sec.)  in  a  capillary  of  20  /x  diameter, 
and  one-fourth  as  great  (or  ^  mm.  per  sec.)  in  a  capillary  of  5  /x  diameter, 
the  pressure  being  supposed  equal  in  all.  The  volume  of  outflow  per 
second  is  obtained  by  multiplying  the  cross-section  by  the  linear 
velocity.  The  cross-section  of  a  circular  capillary,  10  /x  in  diameter, 
is  IT  (5  X  yjJjjij)^  =,  say,  \-^}r,i)  sq.  mm.  The  outflow  will  be  i^lwa'^^ 
—  usooo  ^"^-  mm.  per  sec.  The  outflow  from  the  capillary  of  .'.o  /x 
diameter  would  be  sixteen  times  as  muQh,  from  the  5  /x  capillary  only 
one-sixteenth  as  much.  Some  idea  of  the  extremely  minute  scale 
on  which  the  blood-flow  through  a  single  capillar^'  takes  place  may 
be  obtained  if  we  consider  that  for  the  capillary  of  10  /x  diameter  a 
flow  of  ^7-^00  cub.  mm.  per  sec.  would  scarcely  amount  to  i  cub.  mm 
in  six  hours,  or  to  i  c.c.  in  250  days. 

When  the  initial  energy  is  obtained  in  any  other  way  than  by  means 
of  a  '  head  '  of  water  in  a  reservoir — say,  by  the  descent  of  a  piston 
which  keeps  up  a  constant  pressure  in  a  cylinder  filled  with  liquid — 
the  results  are  exactly  the  same.  Even  when  the  horizontal  tube  is 
distensible  and  elastic,  there  is  no  difference  when  once  the  tube  has 
taken  up  its  position  of  equilibrium  for  any  given  pressure,  and  that 
pressure  docs  not  varj-. 

Flow  with  Intermittent  Pressure. — When  this  acts  on  a  rigid  tube 
everything  is   the   same   as   before.     When   the   pressure   alters,    the 
flow  at  once   comes  to   correspond   with  the   new   pressure.     Water 
thrown  by  a  force-pump  into  a  system  of  rigid  tubes  escapes  at  every 
stroke  of  the  pump  in  exactly  the  quantity  in  which  it  enters,  for 
water  is  practically  incompressible,   and   the   total   quantity  present 
at  one  time  in  the  system  cannot  be  sensibly  altered.     In  the  intervals 
between  the  strokes  the  flow  ceases;  in  other  words,  it  is  intermittent. 
It  is  very  different  with  a  system  of  distensible  and  elastic  tubes. 
During  each  stroke  the  tubes  expand,  and  make  room  for  a  portion 
of  the  extra  liquid  thrown  into  them,  so  that  a  smaller  quantity  flows  \ 
out  than  passes  in.     In  the  intervals  between  the  strokes  the  distended  I 
tubes,  in  virtue  of  their  elasticity,  tend  to  regain  their  original  calibre.  ! 
Pressure  is  thus  exerted  upon  the  liquid,  and  it  continues  to  be  forced  * 
out,  so  that  when  the  strokes  of  the  pump  succeed  each  other  with  ; 
sufficient  rapidity,  the  outflow  becomes  continuous.     This  is  the  state 
of  affairs   in   the   vascular  system.     The   intermittent   action   of   the 
heart  is  toned  down  in  the  elastic  vessels  to  a  continuous  steady  flow. 

Section  II. — The  Be.\t  of  the  He.art  in  its  Physical  or 
Mechanical  Relations. 

Events  in  the  Cardiac  Cycle. — In  the  frog's  heart  the  contraction 
can  be  seen  to  begin  about  the  mouths  of  the  great  veins  which  open 
into  the  sinus  venosus.     Thence  it  spreads  in  succession  over  the 


86  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

sinus  and  auricles,  hesitates  for  a  moment  at  the  auriculo-ventric- 
ular  junction,  and  then  with  a  certain  suddenness  invades  the 
ventricle.  In  the  mammalian  heart  the  contraction  likewise  com- 
mences, so  far  as  can  be  ascertained  by  inspection  or  the  study  of 
tracings,  in  the  region  near  the  mouths  of  the  veins  opening  into  the 
auricles.  It  will  be  seen,  when  the  question  of  the  origin  of  the 
rhythmical  beat  is  being  discussed  (p.  141),  that  the  actual  starting- 
point  is  probably  the  sinus  tissue  of  the  right  auricle  (p.  142)  near  the 
opening  of  the  superior  vena  cava,  which  is  richly  provided  with 
muscular  fibres  akin  to  those  of  the  heart.  But  the  wave  advances 
so  rapidly  that  it  is  difficult  to  trace  in  its  course  a  regular  progress 
from  base  to  apex,  although  the  ventricular  beat  undoubtedly 
follows  that  of  the  auricle,  and  in  a  heart  beating  normally  the 
electrical  change  associated  with  contraction  of  the  ventricle 
begins  at  the  base,  then  reaches  the  apex  (p.  806),  and  finally  passes 
towards  the  orifices  of  the  great  arteries. 

The  most  conspicuous  events  in  the  beat  of  the  heart,  in  their 
normal  sequence,  are:  (i)  the  auricular  contraction  or  systole,  (2)  the 
ventricular  contraction  or  systole,  each  followed  by  relaxation,  (3)  the 
pause.  The  auricles,  into  which,  and  beyond  which  into  the  ven- 
tricles, blood  has  been  flowing  during  the  pause  from  the  great 
thoracic  veins,  contract  sharply,  the  right,  perhaps,  a  little  before 
the  left.  The  contraction  begins  in  the  muscular  tissue  that 
surrounds  the  orifices  of  the  veins,  so  that  these,  destitute  of  valves 
as  they  are,  are  functionally,  at  least,  if  not  anatomically,  sealed  up 
for  an  instant,  and  regurgitation  of  blood  into  them  is  to  a  great 
extent,  if  not  entirely,  prevented.  Apparently,  complete  closure 
of  the  inferior  cava  is  unnecessary,  the  pressure  of  the  blood  in  it 
being  sufficiently  high  to  hinder  any  important  back-flow.  The 
action  of  the  circular  fibres  of  the  veins  in  closing  their  orifices  is 
reinforced  by  the  contraction  of  a  band  of  muscle  (the  tcenia  ter- 
minalis)  in  the  roof  of  the  right  auricle.  This  band  compresses 
especially  the  mouth  of  the  superior  vena  cava.  The  filling  of  the 
ventricles  is  thus  completed.  The  actual  amount  of  extra  blood 
injected  into  the  ventricles  by  the  auricular  contraction  is  not  large. 
The  ventricles  are  already  nearly  charged,  but  the  auricles,  so  to 
speak,  ram  the  charge  home.  The  ventricular  contraction  follows 
hard  on  the  relaxation  of  the  auricles.  The  mitral  and  tricuspid 
valves,  whose  strong  but  delicate  curtains  have  during  the  diastole 
been  hanging  down  into  the  ventricles  and  swinging  freely  in  the 
entering  current  of  blood,  are  floated  up  as  the  intraventricular 
pressure  begins  to  rise,  so  that,  in  the  first  moment  of  the  sudden 
and  powerful  ventricular  systole,  the  free  edges  of  their  segments 
come  together,  and  the  auriculo-ventricular  orifices  are  completely 
closed  (Fig.  98,  p.  204).  In  the  measure  in  which  the  pressure  in  the 
contracting  ventricles  increases,  the  contact  of  the  valvular  seg- 


MECHANICS  OF  THE  HEART-BEAT  87 

mcnts  becomes  closer  and  more  extensive;  and  their  tendency  to 
belly  into  the  auricles  is  opposed  by  the  pull  of  the  chordge  tendineae, 
whose  slender  cords,  inserted  into  the  valves  from  border  to  base,  are 
kept  taut,  in  spite  of  the  shortening  of  the  ventricles  by  the  con- 
traction of  the  papillary  muscles.  The  arrangement  and  connec- 
tions of  the  muscular  fibres  of  the  heart  are  such  that  during  the 
auricular  systole  the  auriculo-ventricular  groove  moves  towards  the 
base  of  the  heart,  while  during  the  systole  of  the  ventricles  it  moves 
towards  the  apex,  which  constitutes  a  relatively  fixed  point  on 
account  of  the  mutual  action  of  the  numerous  fibres  which  converge 
here  and  constitute  the  '  whorl.'  The  line  joining  the  apex  and 
the  origin  of  the  aorta  does  not  shorten  when  the  ventricles  contract, 
but  all  parts  of  the  heart  are  drawn  towards  this  line.  The  apex  is, 
therefore,  pushed  forwards,  while  the  rest  of  the  ventricular  surface 
is  being  drawn  inwards.  During  the  systole,  the  ventricles  change 
their  shape  in  such  a  way  that  their  combined  cross-section — which 
in  the  relaxed  state  is  a  rough  ellipse  with  the  major  axis  from  right 
to  left — becomes  approximately  circular,  and  they  then  form  a  right 
circular  cone.  As  soon  as  the  pressure  of  the  blood  within  the  con- 
tracting ventricles  exceeds  that  in  the  aorta  and  pulmonary  artery 
respectively,  the  semilunar  valves,  which  at  the  beginning  of  the 
ventricular  systole  are  closed,  yield  to  the  pressure,  and  blood  is 
driven  from  the  ventricles  into  these  arteries. 

The  ventricles  are  more  or  less  completely  emptied  during  the 
contraction,  which  seems  still  to  be  maintained  for  a  short  time  after 
the  blood  has  ceased  to  pass  out.  The  contraction  is  followed 
by  sudden  relaxation.  The  intraventricular  pressure  falls.  The 
lunules  of  the  semilunar  valves  slap  together  under  the  weight  of  the 
blood  as  it  attempts  to  regurgitate,  the  corpora  Arantii  seal  up  the 
central  chink,  and  the  aorta  and  pulmonary  artery  are  thus  cut  off 
from  the  heart.  Then  follows  an  interval  during  which  the  whole 
heart  is  at  rest,  namely,  the  interval  between  the  end  of  the  relaxa- 
tion of  the  ventricles  and  the  beginning  of  the  systole  of  the  auricles. 
This  constitutes  the  pause.  The  whole  series  of  events  is  called  a 
cardiac  cycle  or  revolution  (see  Practical  Exercises,  p.  199). 

It  will  be  easily  understood  that  the  time  occupied  by  any  one  of 
the  events  of  the  cardiac  cycle  is  not  constant,  for  the  rate  of  the 
heart  is  variable.  If  we  take  about  70  beats  a  minute  as  the  average 
normal  rate  in  a  man,  the  ventricular  systole  will  occupy  about 
0'3  second;  the  diastole,*  including  the  ventricular  relaxation,  about 

*  The  term  '  diastole  '  is  variously  used,  as  meaning  the  pause,  the  pause 
plus  the  period  during  which  relaxation  is  occurring,  or  the  period  of  re- 
laxation alone.  We  shall  employ  it  in  the  second  sense.  Henderson  refers 
to  the  period  during  which  the  ventricular  muscle  is  at  rest,  from  the  end  of 
its  relaxation  to  the  onset  of  the  auricular  systole,  as  the  'diastasis'  and  the 
period  during  which  the  relaxation  is  taking  place  as  the  'diastole,'  a  termin- 
ology which  seems  worthy  of  general  adoption. 


88  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

0-5  second.  The  systole  of  the  auricle  is  one-third  as  long  as  that  of 
the  ventricle. 

This  rhythmical  beat  of  the  heart  is  the  ground  phenomenon  of 
the  circulation.  It  reveals  itself  by  certain  tokens — sounds,  surface- 
movements  or  pulsations,  alterations  of  the  pressure  and  velocity  of 
the  blood,  changes  of  volume  in  parts — -all  periodic  phenomena, 
continually  recurring  with  the  same  period  as  the  heart-beat,  and  all 
fundamentally  connected  together.  And  if  we  hold  fast  the  idea 
that  when  we  take  a  pulse-tracing,  or  a  blood-pressure  curve,  or  a 
plethysmographic  record,  we  are  really  investigating  the  same  fact 
from  different  sides,  we  shall  be  able,  by  following  the  cardiac  rhythm 
and  its  consequences  as  far  as  we  can  trace  them,  to  hang  upon  a 
single  thread  many  of  the  most  important  of  the  physical  phenom- 
ena of  the  circulation. 

The  Sounds  of  the  Heart. — When  the  ear  is  applied  to  the  chest,  or 
to  a  stethoscope  placed  over  the  cardiac  region,  two  sounds  are 
heard  with  every  beat  of  the  heart.  They  follow  each  other  closely, 
and  are  succeeded  by  a  period  of  silence.  The  dull  booming  '  first 
sound  '  is  heard  loudest  in  a  region  which  we  shall  afterwards  have 
to  speak  of  as  that  of  the  '  cardiac  impulse  '  (p.  90) ;  the  short,  sharp, 
'  second  sound  '  over  the  junction  of  the  second  right  costal  cartilage 
with  the  sternum. 

The  heart-sounds  can  be  registered  by  plncing  over  the  chest  a 
microphone  receiver  connected  with  a  string  galvanometer.  The 
magnified  sounds  are  translated  into  electrical  changes  which  cause 
movements  of  the  fibre  of  the  galvanometer,  and  the  movements  are 
photographed  on  a  travelUng  plate  (Einthoven).  The  record  is  called 
a  cardiophonogram.  When  this  is  studied,  a  third  sound  can  be 
detected,  and  it  is  probable  that  it  is  present  in  all  persons,  although  it 
is  as  a  rule  inaudible  to  auscultation.  It  occurs  early  in  diastole  very 
shortly  after  the  second  sound.  In  those  persons  in  whom  it  is  audible 
it  is  most  distinct  over  the  region  of  cardiac  impulse.  It  is  described 
as  softer  and  of  lower  pitch  than  the  second  sound  (Thayer). 

There  has  been  much  discussion  as  to  the  cause  of  the  first  sound. 
That  a  sound  corresponding  with  it  in  time  is  heard  in  an  excised 
bloodless  heart  when  it  contracts  is  certain;  and  therefore  the  first 
sound  cannot  be  exclusively  due,  as  some  have  asserted,  to  vibra- 
tions of  the  auriculo-ventricular  valves  when  they  are  suddenly 
lendered  tense  by  the  contraction  of  the  ventricles,  for  in  a  bloodless 
heart  the  valves  are  not  stretched.  Part  of  the  sound  must  accord- 
ingly be  associated  with  the  muscular  contraction  as  such. 

Again,  the  fact  that  the  first  sound  is  heard  during  the  whole,  or 
nearly  the  whole,  of  the  ventricular  systole  is  against  the  idea  that 
it  is  exclusively  due  to  the  vibrations  of  membranes  like  the  valves, 
which  would  speedily  be  damped  by  the  blood  and  rendered  in- 
audible. But  while  there  is  good  reason  to  believe  that  the  vibra- 
tion of  the  suddenly-contracted  ventricles  is  the  fundamental  factor, 
the  shock  sets  up  vibrations  also  in  the  blood,  the  chest-wall,  and 


MECHANICS  OF  THE  HEART-BEAT  89 

perhaps  the  resonant  tissue  of  the  lungs.  Further,  as  we  shall  see 
later  on  (p.  734),  the  sound  caused  by  a  contracting  muscle  readily 
calls  forth  sympathetic  resonance  in  the  ear,  and  the  peculiar  boom- 
ing character  of  the  first  sound  may  be  due  to  the  superposition  of 
these  various  resonance  tones  upon  the  muscular  note.  But,  in 
addition,  the  vibration  of  the  auriculo-ventricular  valves  un- 
doubtedly contributes  to  the  production  of  the  sound,  and  some 
observers  have  been  able  to  distinguish  in  the  first  sound  the  valvular 
and  the  muscular  elements,  the  former  being  higher  in  pitch  than  the 
latter,  but  a  minor  third  below  the  second  sound.  In  the  excised 
empty  heart  the  deeper  tone  of  the  first  sound  is  alone  heard,  while 
the  higher  note  is  elicited  when  in  a  dead  heart  the  auriculo-ventric- 
ular valves  are  suddenly  put  under  tension  (Haycraft).  When  the 
mitral  valve  is  prevented  from  closing  by  experimental  division  of 
the  chordse  tendines,  or  by  pathological  lesions,  the  first  sound  of 
the  heart  is  altered  or  replaced  by  a  '  murmur.'  This  evidence  is 
not  only  important  as  regards  the  phj^siological  question,  but  of 
great  practical  interest  from  its  bearing  on  the  diagnosis  of  cardiac 
disease.  It  may  be  added  that  the  point  of  the  chest-wall  at  which 
the  first  sound  is  most  easily  recognized  is  also  the  point  at  which  a 
changed  sound  or  murmur  connected  with  disease  of  the  mitral  valve 
is  most  distinctly  heard.  The  sound  is,  therefore,  best  conducted 
from  the  mitral  valve  along  the  heart  to  the  point  at  which  it  comes 
in  contact  with  the  wall  of  the  chest.  Changes  in  the  first  sound  con- 
nected with  disease  of  the  tricuspid  valve  are  heard  best,  in  the  com- 
paratively rare  cases  where  they  can  be  distinctly  recognized,  in  the 
third  to  the  fifth  interspace,  a  little  to  the  right  of  the  sternum. 

The  second  sound  is  caused  by  the  vibrations  of  the  semilunar 
valves  when  suddenly  closed, '  the  recoiUng  blood  forcing  them  back, 
as  one  unfurls  an  umbrella,  and  with  an  audible  check  as  they 
tighten  '  (Watson).  The  sharpness  of  its  note  is  lost,  and  nothing 
but  a  rushing  noise  or  bruit  can  be  heard,  when  the  valves  are  hooked 
back  and  prevented  from  closing.  It  is  altered,  or  replaced  by  a 
murmur,  when  the  valves  are  diseased.  As  there  is  a  mitral  and  a 
tricuspid  factor  in  the  first  sound,  so  there  is  an  aortic  and  a  pul- 
monary factor  in  the  second.  .  The  place  where  the  second  sound  is 
best  heard  (over  the  junction  of  the  second  right  costal  cartilage  and 
sternum)  is  that  at  which  any  change  produced  by  disease  of  the 
aortic  valves  is  most  easily  recognized.  The  sound  is  conducted  up 
from  the  valves  along  the  aorta,  which  comes  nearest  to  the  surface 
at  this  point.  Changes  connected  with  disease  of  the  pulmonary 
valves  are  mcfst  readily  detected  over  the  second  left  intercostal 
space  near  the  edge  of  the  sternum,  for  here  the  pulmonary  artery 
most  nearly  approaches  the  chest-wall.  The  first  sound  is  '  systolic  ' 
— that  is,  it  occurs  during  the  ventricular  systole;  the  second  is 
'  diastolic,'  beginning  at  the  commencement  of  the  diastole 


90 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


Various  explanations  of  the  third  sound  have  been  given,  but,  as 
the  authors  who  have  studied  it  are  not  even  agreed  as  to  whether  it 
is  produced  at  the  auriculo-ventricular  orifices  or  at  the  aortic  and 
pulmonary  orifices,  it  would  not  be  useful  to  discuss  them  at  present. 
The  Cardiac  Impulse. — A  surface-movement  is  seen,  or  an  impulse 
felt,  at  every  cardiac  contraction  in  various  situations  where  the 
heart  or  arteries  approach  the  surface.  The  pulsation,  or  impulse, 
of  the  heart,  often  styled  the  apex-beat,  is  usually  most  distinct  to 
sight  and  touch  in  a  small  area  lying  in  the  fifth  left  intercostal 
space,  between  the  mammary  and  the  parasternal  line,*  and  gener- 
ally, in  an  adult,  about  an  inch  and  a  half  to  the  sternal  side  of  the 
former.  It  is  due  to  the  systolic  hardening  of  the  ventricles,  which 
are  here  in  contact  with  the  chest-wall,  the  contact  being  at  the 
same  time  rendered  closer  by  th^'-  change  of  shape,  and  by  a  slight 

movement  of  rotation  of 
the  heart  from  left  to  right 
during  the  contraction 
(Practical  Exercises, 
p.  205).  When  the  left 
ventricle  is  in  contact  with 
the  chest  at  the  position  of 
the  apex-beat,  as  is  usually 
the  case,  an  important 
element  in  the  impulse  is 
the  actual  forward  thrust 
of  the  apex.  When  the 
apex-beat  corresponds  in 
position  with  the  right 
ventricle,  there  is  no 
actual  forward  movement, 
although  the  hardening  of 
the  ventricle  may  be  felt  as  a  tlirust  by  the  finger.  Even  in  health 
the  position  of  the  impulse  varies  somewhat  with  the  position  of 
the  body  and  the  respiratory  movements.  In  children  it  is  usually 
situated  in  the  fourth  intercostal  space.  In  disease  its  displacement 
is  an  important  diagnostic  sign,  and  may  be  very  marked,  especially 
in  cases  of  effusion  of  fluid  into  the  pleural  cavity.  It  is  sometimes, 
though  not  invariably,  a  httle  lower  in  the  standing  than  in  the 
sitting  position,  and  shifts  an  inch  or  two  to  the  left  or  right  when 
the  person  hes  on  the  corresponding  side. 

Various  instruments,  called  cardiographs,  have  been  devised  for 
magnifying  and  recording  the  movements  produced  by  the  cardiac 
impulse.     Marey's  cardiograph  (Fig.  27)  consists  essentially  of  a  small 

*  The  mammary  line  is  ^n  imaginary  vertical  line  supposed  to  be  drawn 
on  the  chest  through  the  aiddle  point  of  the  clavicle.  It  usually,  but  not 
necessarily,  passes  through  tne  nipple.  The  parasternal  line  is  the  vertical 
line  lying  midway  between  the  mammary  line  and  the  corresponding  border 
of  the  sternum. 


Fig.  27. — Diagram  of  Marey's  Cardiograph. 


MECHANICS  OF  THE  HEART-  BEAT  91 

chamber,  or  tambour,  filled  with  air,  and  closed  at  one  end  by  a  flexible 
membrane  carrying  a  button,  which  can  be  adjusted  to  the  wall  of  the 
chest.  This  receiving  tambour  is  connected  by  a  tube  with  a  recording 
tambour,  the  flexible  plate  of  which  acts  upon  a  lever  writing  on  a 
travelling  surface — a  uniformly-rotating  drum,  for  example — covered 
with  smoked  paper.  Any  movement  communicated  to  the  button 
forces  in  the  end  of  the  tambour  to  which  it  is  attached,  and  thus 
raises  the  pressure  of  the  air  in  it  and  in  the  recording  tambour;  the 
flexible  plate  of  the  latter  moves  in  response,  and  the  lever  transfers 
the  movement  to  the  paper.  The  tracing,  or  cardiogram,  obtained  in 
this  way  shows  a  small  elevation  corresponding  to  the  auricular  systole, 
succeeded  by  a  large  abrupt  rise  corresponding  to  the  beginning  of 
the  first  sound,  and  caused  by  the  ventricular  systole.  This  ventricular 
elevation  is  the  essential  portion  of  the  curve;  it  is  alone  felt  by  the 
palpating  hand,  and  the  auricular  elevation  is  often  absent  from  the 
cardiogram  in  man.  The  rise  is  maintained,  with  small  secondary 
oscillations,  for  about  o-;5  of  a  second  in  a  tracing  from  a  normal  man, 
then  gives  way  to  a  sudden  de- 
scent, that  marks  the  relaxation 
of  the  ventricles,  the  beginning 
of  the  second  sound,  and  the 
closure  of  the  semilunar  valves. 
An  interval  of  about  0-5  second 
elapses  before  the  curve  begins 
again  to  rise  at  the  next  auricukir 
contraction. 

Such  was  the  interpretation 
which  Chauveau  and  Marey  put 
upon  their  tracings.  Although 
neither  their  results  nor  their 
deductions  from  them  have  ^^S-  28,— Cardiogram  taken  with  Marey's 
escaped  the  criticism  of  succeed-  Cardiograph.  A,  auricular  systole; 
ing  investigators,  it  is  doubtful         1:     ventricular     systole ;     D.    diastole. 

whether    anv    adeauate    reason         ^^^  ^"°'''  ^^^"^^  ^^^  direction  in  which 
wnetner    any    aaequate    reason         ^j^^  tracing  is  to  be  read, 
has   been    brought   forward   for 

discarding  them,  and  Chauveau  has  furnished  further  proofs  of  their 
accuracy.  The  difficulties  that  beset  the  subject  are  great,  for  the 
cardiogram  is  a  record  of  a  complex  series  of  events.  The  very  rapid 
variation  of  pressure  within  the  ventricles,  the  change  of  volume  and 
of  shape  of  the  heart,  the  slight  change  of  position  of  its  apex,  must 
all  leave  their  mark  upon  the  curve,  which  is  besides  distorted  by  the 
resistance  of  the  elastic  chest-wall,  the  inertia  of  the  recording  lever, 
and  the  compression  of  the  air  in  the  connecting  tubes.  It  is  only  by 
comparing  in  animals  the  cardiographic  record  with  the  changes  of 
blood-pressure  in  the  heart  and  arteries  that  our  present  degree  of 
knowledge  of  the  human  cardiogram  has  been  attained.  Could  we 
register  directly  the  fluctuations  of  pressure  in  the  interior  of  the  human 
heart,  the  cardiographic  method  would  be  rarely  employed.  For 
clinical  purposes  the  receiving  tambour  can  be  advantageously  replaced 
by  a  small  glass  funnel  or  a  small  metal  cup,  the  open  end  of  which  is 
applied  without  a  membrane  over  the  cardiac  impulse,  the  stem  being 
connected  with  the  recording  tambour.  In  cases  in  which  the  right 
ventricle  is  in  contact  with  the  chest-wall  at  the  position  of  the  apex- 
beat  the  cardiogram  is  '  inverted  ' — that  is  to  say,  the  chest-wall  is 
drawn  in  during  systole  and  protruded  during  diastole  of  the  ventricles. 
Inversion  of  the  cardiogram  is,  therefore,  not  an  infallible  sign  of  the 
pathological  condition  known  as  adherent  pericardium  (Mackenzie). 


92 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


Endocardiac  Pressure.— The  function  of  the  heart  is  to  niaintain 
an  excess  of  pressure  in  the  aorta  and  pulmonary  artery  sufficient  to 
overcome  the  friction  of  the  whole  vascular  channel,  and  to  keep  up 
the  flow  of  blood.  So  long  as  the  semilunar  valves  are  closed,  most 
of  the  work  of  the  contracting  ventricles  is  expended  in  raising  the 
pressure  of  the  blood  within  them.  At  the  moment  when  blood 
begins  to  pass  into  the  arteries,  nearly  all  the  energy  of  this  blood  is 
potential;  it  is  the  energy  of  a  Hquid  under  pressure.  During  a 
cardiac  cycle  the  pressure  in  the  cavities  of  the  heart,  or  the  endo- 
cardiac pressure,  varies  from  moment  to  moment,  and  its  variations 

afford  important 
data  for  the  study 
of  the  mechanics  of 
the  circulation. 

Manometers.  — For 

the  study  of  the  endo- 
cardiac pressure,  the 
ordinary  mercurial 
manometer  (p.  no) 
is  unsuitable,  since, 
owing  to  the  rela- 
tively great  amount 
of  work  required  to 
produce  a  given  dis- 
placement of  the  mer- 
cury, it  does  not 
readily  follow  rapid 
changes  of  pressure, 
and  the  mercurial 
column,  once  dis- 
placed, continues  for 
a  time  to  execute 
vibrations  of  its  own, 
which  are  compoun- 
ded with  the  true  oscillations  of  blood-pressure.  But  by  introducing 
in  the  connection  between  the  manometer  and  the  heart  a  valve  so 
arranged  as  to  oppose  the  passage  of  blood  towards  the  heart,  while  it 
favours  its  passage  towards  the  manometer,  the  maximum  pressure 
attained  in  the  cardiac  cavities  during  the  cycle  may  be  measured  with 
considerable  accuracy.  When  the  valve  is  reversed  the  apparatus 
becomes  a  minimum  manometer.  In  this  way  it  has  been  found  that 
in  large  dogs  the  pressure  in  the  left  ventricle  may  rise  as  high  as  230 
to  240  mm.  of  mercury,  and  sink  as  low  as  -  30  to  -  50  mm. ;  while  in 
the  right  ventricle  it  may  be  as  much  as  70  mm.,  and  as  little  as 
—  25  mm.  In  the  right  auricle  a  maximum  pressure  of  20  mm.  of 
mercury  has  been  recorded,  and  a  minimum  pressure  of  —  10  mm.  or 
even  less.  But  these  results  were  obtained  under  somewhat  exceptional 
experimental  conditions,  and  the  normal  maximum  pressures  in  the 
heart  cavities  in  man  are  probably  not  so  high,  especially  in  the  right 
auricle  and  ventricle. 

Our  knowledge  of  the  maximum  and  minimum  pressure  attained 
in  the  cavities  of  the  heart,  even  if  it  were  far  more  precise  than  it 
actually  is,  would  only  carry  us  a  little  way  in  the  study  of  the  endo- 
cardiac pressure-curve,  for  it  would  merely  tell  us  how  far  above  the 


Fig.  29. — Curves  of  Endocardiac  Pressure  taken  with 
Cardiac  Sounds.  Aur.,  auricular  curve;  Vent.,  ven- 
tricular curve;  AS,  period  of  auricular  systole,  in- 
cluding relaxation;  VS,  of  ventricular  systole, including 
relaxation;  D,  pause. 


MECHANICS  OF  THE  HEART-BEAT 


93 


T.  ^^ 

Fig.  30. — Diagram  of  Hurthle's  Elastic  Mano- 
meter. T,  small  chamber  covered  by  mem- 
brane; I.  tube  communicating  with  interior 
of  heart;  L.  compound  lever  to  magnify  the 
movements  of  the  membrane. 


base-line  of  atmospheric  pressure  the  curve  ascends,  and  how  far  below 
the  base-line  it  sinks.  To  exhaust  the  problem,  we  require  to  have 
tracings  of  the  exact  form  of  the  curve  for  each  of  the  cavities  of  the 
heart,  and  to  know  the  time-relations  of  the  curves  so  as  to  be  able  to 
compare  them  with  each  other,  and  with  the  pressure-curves  of  the  great 
arteries  and  great  veins.  To  obtain  satisfactory  tracings  of  the  swiftly- 
changing  endocardiac  pressure 
is  a  task  of  the  highest  techni- 
cal difficulty,  and  it  is  only  in 
very  recent  years  that  it  has 
been  accomplished,  with  any  ap- 
proach to  accuracy  by  the  use 
of  elastic  manometers,  in  which 
the  blood-pressure  is  counter- 
balanced, riot  by  the  weight  of 
a  column  of  liquid,  as  in  the 
mercurial  manometer,  but  by 
the  resistance  to  compression 
of  a  small  column  of  air  or  the 
tension  of  an  elastic  disc  or  of 
a  spring.  Modifications  in  the 
nature  and  dimensions  of  the  elastic  resistance  of  the  recording  apparatus 
and  of  the  size  of  the  cavity  have  produced  successive  improvements,  as, 
e.g.,  in  the  manometers  of'^Hiirthle  (Fig   30). 

The  penetrating  analysis  of  the  principles  of  manometer  construction 
by  Frank  has  recently  stimulated  renewed  investigation  of  the  whole 
subject  with  the  aid  of  instruments  whose  movements  are  optically  re- 


Fig.  31. — Diagram  of  Opticad  Manometer  (Wiggers). 
A  is  a  vertical  glass  tube  surmoimted  by  a  hollow 
brass  cylinder,  B,  which  contains  a  stopcock,  C. 
whose  lumen  comes  into  apposition  with  a  plate, 
a,  having  a  small  opening  in  it.  By  opening  the 
stopcock  more  or  less,  the  pulsations  will  be  '  damped ' 
to  a  smaller  or  greater  extent.  Above  a  the  cylinder 
ends  in  a  segment  capsule  b  (i.e.,  a  capsule  cut  away 
at  one  side)  3  mm.  in  diameter,  covered  with  rubber 
dam.  Upon  this  a  small  piece  of  celluloid  carrying 
a  little  mirror,  c,  is  fastened,  so  that  it  pivots  on  the 
chord  side  of  the  capsule.  Over  the  capsule  and  its 
recording  mirror  is  mounted  a  support  bearing  an 
inclined  reflecting  mirror,  E,  adjustable  about  a 
horizontal  axis  by  a  screw,  so  that  the  image  of  the 
I  ecording  mirror  appears  within  it.  Upon  this 
miage  a  strong  light  is  focussed.  The  incident  rays 
are  doubly  reflected,  as  shown  in  the  figure,  and  the 
movements  of  the  capsule  are  thus  greatly  magnified. 
The  beam  of  light  is  photographed  on  a  moving 
plate. 


corded  on  a  photographic  plate,  so  as  to  eliminate  all  unnecessary  fric- 
tion. Fig.  31  is  a  diagram  of  the  manometer  devised  by  Wiggers  on 
this  principle. 

Hiirthle's  spring  manometer  consists  of  a  small  drum  covered  with 
an  indiarubber  membrane,  loosely  arranged  so  as  not  to  vibrate  with 
a  period  of  its  own.  The  drum  is  connected  with  the  heart  or  with 
a  vessel,  and  the  blood-pressure  is  transmitted  to  a  steel  spring  by 
means  of  a  light  metal  disc  fastened  on  the  membrane.     The  spring 


94  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

acts  on  a  writing  lever.  The  instrument  is  so  constructed  that  for  a 
given  change  of  pressure  the  quantity  of  liquid  displaced  is  as  small 
as  possible,  and  it  is  on  this  that  its  capacity  to  follow  sudden  varia- 
tions of  pressure  chiefly  depends.  The  manometer  is  connected  with 
the  cavity  of  the  heart  by  an  appropriately  curved  cannula  of  metal 
or  glass,  which,  after  being  filled  with  some  liquid  that  prevents  co- 
agulation (Practical  Exercises,  p.  209),  is  pushed  through  the  jugular 
vein  into  the  right  auricle  or  ventricle,  or  through  the  carotid  artery 
and  aorta  into  the  left  ventricle.  Some  observers  fill  only  the  cannula 
with  fluid,  and  leave  the  capsule  of  the  elastic  manometer  and  as  much 
of  the  connections  as  possible  full  of  air.  Others  fill  the  whole  system 
with  liquid.  And  around  the  question  of  the  relative  merits  of  '  trans- 
mission '  by  liquid  and  by  air  has  raged  a  controversy  which,  however, 
now  shows  signs  of  coming  to  an  end.  For  there  is  reason  to  suppose 
that  the  character  of  the  curves  obtained  is  modified  among  other 
circumstances  by  the  manner  in  which  the  pressure  is  transmitted,  as 
it  is  certainly  modified  by  the  dimensions  and  mass  of  the  moving  parts 
and  the  method  of  recording.  As  Wiggers  has  pointed  out,  the  differ- 
ences in  the  records  obtained  by  different  observers,  even  with  the  latest 
methods  of  optical  registration,  are  determined  largely  by  the  sensitive- 
ness and  degree  of  damping  of  the  manometer. 

The  Ventricular  Pressure-Curve. — Thus,  the  pressure-curve  of  the 
ventricle,  according  to  most  of  those  who  have  employed  mano- 
meters with  liquid  transmission  and  small  inertia  of  the  moving 
parts  (Fig.  33),  remains  after  the  first  abrupt  rise,  which  undoubtedly 
corresponds  to  the  ventricular  systole,  well  above  the  abscissa  line 
for  a  considerable  time,  and  then  descends  somewhat  less  suddenly 
than  it  rose.  This  systolic  '  plateau,'  although  usually  broken  by 
minor  heights  and  hollows,  which  may  be  partly  due  to  inertia  oscilla- 
tions of  the  liquid  or  the  recording  apparatus,  would  indicate  that 
the  ventricular  pressure,  after  its  first  swift  rise,  maintained  itself  at 
a  considerable  height  throughout  the  greater  part  of  the  systole.. 
The  tracings  yielded  by  most  of  the  manometers  with  air  trans- 
mission show  the  same  suddenness  in  the  first  part  of  the  upstroke 
and  the  last  part  of  the  descent — ^that  is,  the  same  abruptness 
in  the  beginning  of  the  contraction  and  the  end  of  the  relaxa- 
tion. But  they  differ  totally  in  the  intermediate  portion  of  the 
curve,  which,  climbing  ever  more  gradually  as  it  nears  its  apex, 
remains  but  a  moment  at  the  maximum,  then  immediately  descend- 
ing forms  a  '  peak,'  and  not  a  plateau.  It  ought  to  be  distinctly 
understood,  however,  that  the  use  of  the  term  '  plateau  '  must  not  be 
taken  to  imply  that  the  pressure  remains  constant  and  the 'curve 
parallel  to  the  abscissa  during  this  interval. 

Wiggers,  using  the  optical  method  of  recording  the  pressure- 
curve  in  the  right  ventricle  (p.  93),  finds  that  when  the  auricular 
pressure  and  the  pressure  in  the  pulmonary  artery  are  normal  the 
curve  of  intraventricular  pressure  may  be  divided  into  (i)  an  auric- 
ular period;  (2)  a  period  of  rising  pressure  while  the  ventricle  is 
contracting  and  its  cavity  is  closed  by  the  auriculo- ventricular  and 
semilunar  valves;  (3)  an  ejection  period  during  which  the  pressure 


MECHANICS  OF  THE  HEART-BEAT 


95 


stiir rises,  reaches  a  summit,  and  then  slowly  falls;  and  (4)  a  relaxa- 
tion period  (Fig.  32). 

Without  entering  further  into  a  technical  discussion,  we  may  say 


Cu'otifi 


V  .  ^[\ 


h  [ 


rig.  32. — Intraventricular  Pressure  Curves  with  Optical  Recording  (Wiggers).  Three 
types  of  normal  curves  are  reproduced,  taken  with  manometers  of  different 
degrees  of  sensitiveness.  The  second  at  the  left-hand  side  was  taken  with  the 
least  sensitive,  a — b.  auricular  systolic;  b — d,  isometric  period,  during  which 
the  auriculo-ventricular  and  the  semilunar  valves  cire  both  closed;  d — f,  ejection 
period ;  after  /,  diastole. 

the  bulk  of  the  evidence  goes  to  show  that  the  plateau  is  not,  as  the 
advocates  of  the  peak  have  claimed,  an  artificial  phenomenon,  but 
does  in  reality  correspond  to  that  continuation  of  the  systole  of  the 


\ihh/\\\'^\\\i^'Mfymmy^\^^ 


Fig-  33- — Simultaneous  Record  of  Pressure  in  Left  Ventricle  (V)  and  Aorta  (.A). 
(Hiirthle.)  The  tracings  were  taken  with  elastic  manometers;  o  indicates  a 
point  just  before  the  closure  of  the  mitral  valve;  i,  the  opening  of  the  semilunar 
valve;  2,  beginning  of  the  relaxation  of  the  ventricle;  3,  the  closure  of  the  semi- 
lunar valve;  4,  the  opening  of  the  mitral  valve.  The  ventricular  curve  shows 
a  '  plateau.' 

ventricle,  that  dogged  grip,  if  we  may  so  phrase  it,  which  it  seems  to 
maintain  upon  the  blood  after  the  greater  portion  of  it  has  bet-n 
expelled. 


96  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

This  conclusion  is  essentially  in  accordance  with  the  results  of 
Chauveau  and  Marey,  obtained  long  ago  by  means  of  their  '  cardiac 
sound,'  which  was  in  principle  an  elastic  manometer. 

It  consisted  of  an  ampulla  of  indiarubber,  supported  on  a  frame- 
work, and  communicating  with  a  long  tube,  which  was  connected  with 
a  recording  tambour.  The  ampulla  was  introduced  into  the  heart  (of 
a  horse)  through  the  jugular  vein  or  carotid  artery  in  the  way  already 
described.  Sometimes  a  double  sound  was  employed,  armed  with 
two  ampullae,  placed  at  such  a  distance  from  each  other  that  when 
one  was  in  the  right  ventricle  the  other  was  in  the  auricle  of  the  same 
side.  Each  ampulla  communicated  by  a  separate  tube  in  the  common 
stem  of  the  instrument  with  a  recording  tambour,  and  the  writing 
points  of  the  two  tambours  were  arranged  in  the  same  vertical  line. 
When  any  change  in  the  blood-pressure  takes  place,  the  degree  of 
compression  of  the  ampullae  is  altered,  and  the  change  is  transmitted 
along  the  air-tight  connections  to  the  recording  tambours. 

On  most  of  the  endocardiac  pressure  tracings  taken  with  modern 
manometers,  whether  the  curves  belong  to  the  type  of  the  peak  or  of 
the  plateau,  no  sudden  change  of  curvature,  no  nick,  or  crease,  or 
undulation  reveals  the  moment  of  opening  or  closure  of  any  valve. 
This  has  been  considered  by  some  writers  a  striking  tribute  to  the 
smooth  working  of  the  cardiac  pump.  There  is  reason  to  think, 
however,  that  the  smoothness  of  the  curve  is  still  in  some  degree 
artificial,  and  on  some  of  the  records  obtained  by  optical  methods 
(Fig.  32)  indications  of  changes  of  curvature,  associated  with  the 
'  action  of  the  valves,  may  be  observed.  But  even  in  the  absence  of 
such  indications,  by  experimentally  graduating  a  pair  of  elastic 
manometers,  and  obtaining  with  them  simultaneous  records  of  the 
pressure  in  auricle  and  ventricle,  or  by  using  a  '  differential '  mano- 
meter, in  which  the  pressures  in  two  cavities  are  opposed  to  each 
other,  so  that  the  movement  of  the  membrane  corresponds  to  their 
difference,  we  can  calculate  at  what  points  of  the  ventricular  curve 
the  pressure  is  just  greater  than  and  just  less  than  the  pressure  in  the 
auricle.  The  first  point,  it  is  evident,  will  correspond  to  the  instant 
at  which  the  mitral  or  tricuspid  valve,  as  the  case  may  be,  is  closed, 
and  the  second  to  the  instant  at  which  it  is  opened.  And  in  like 
manner,  by  comparing  the  pressure-curve  of  the  aorta  with  that  of 
the  left  ventricle,  the  moment  of  opening  and  closure  of  the  semi- 
lunar valves  may  be  determined  (Figs.  33  and  34).  According  to  the 
best  observations,  the  closure  of  the  semilunar  valves  takes  place  at 
a  time  corresponding  to  a  point  on  the  upper  portion  of  the  descend- 
ing limb  of  the  intraventricular  curve. 

On  the  blood-pressure  curve  of  the  aorta,  simultaneously  registered, 
the  corresponding  point  is  near  the  bottom  of  the  so-called  '  aortic  ' 
notch  (p.  105)  which  precedes  the  dicrotic  elevation.  For  clinical 
purposes,  in  man  the  moment  of  closure  of  the  semilunar  valves 
(denoted  by  the  abbreviation  S.C.  point)  may  be  taken  as  0-03  second 
before  the  bottom  of  the  aortic  notch  in  sphygmographic  tracings 
from  the  carotid,  this  being  approximately  the  average  time  occupied 


MECHANICS  OF  THE  HEART-BEAT  $7 

by  the  pulse-wave  in  travelling  from  the  aorta  to  the  carotid.  The 
S.C.  point,  the  A.O.  point,  or  moment  of  opening  of  the  auriculo- 
ventricular  valves,  and  the  I  eginning  of  the  ventricular  systole,  are 
three  important  points  of  reference  in  the  measurement  and  inter- 
pretation of  pulse-tracings  in  clinical  work.  The  A.O.  point  in  man 
may  be  taken  as  a  point  '  0-03  second  in  advance  of  the  summit  of 
the  dicrotic  wave  '  on  the  carotid  pulse-tracing  (Lewis).  But  this  is 
the  most  difficult  of  the  three  standard  points  to  determine  clinically 
with  anything  like  accuracy. 

The  study  of  the  curves  of  endocardiac  pressure  enables  us  to  add 
precision  in  certain  points  to  the  description  of  the  events  of  the 
cardiac  cycle  which  we  have  already  given,  and,  as  regards  the 
ventricles,  to  divide  the  cycle  into  four  periods: 

(i)  A  period  during  ■which  the  pressure  is  lower  in  the  ventricles  than 
either  in  the  auricles  or  the  arteries,  and  the  auric ulo-ventricular  valves 
are  consequently  open,  and  the  semilunar  valves  closed.  This  is  the 
period  of  '  filling  '  of  the  heart,  or  the  pause. 

(2)  A  period,  beginning  with  the  ventricular  systole,  during  which  the 
pressure  is  increasing  abruptly  in  the  ventricles,  while  they  are  as  yet 
completely  cut  off  from  the  auricles  on  the  one  hand  and  the  arteries  on 
the  other  by  the  closure  of  both  sets  of  valves.  This  is  the  period  of 
'  rising  pressure,'  during  which  the  ventricles  are,  so  to  say,  '  getting  up 
steam.'  The  interval  between  the  beginning  of  the  ventricular  systole 
and  the  opening  of  the  semilunar  valves  is  termed  the  '  presphygmic  ' 
interval. 

(3)  A  period  during  which  the  pressure  in  the  ventricles  overtops  that 
in  the  arteries,  and  the  semilunar  valves  are  open,  while  the  auriculo- 
ventricular  valves  remain  shut.  This  is  the  period  of  '  discharge  '  or 
'  sphygmic  '  period. 

(4)  A  period  during  which  the  pressure  in  the  ventricles  is  again  less 
than  the  arterial,  while  it  still  exceeds  the  auricular  pressure,  a)id  both 
sets  of  valves  are  closed.  This  is  the  period  of  rapid  relaxation.  The 
interval  between  the  closure  of  the  semilunar  and  the  opening  of  the 
auriculo-ventricular  valves  is  sometimes  called  the  '  post-sphygmic  ' 
interval. 

Of  the  four  periods,  the  second  and  fourth  are  exceedingly  brief. 
The  third  is  relatively  long  and  constant,  being  but  slightly  depen- 
dent on  either  the  pulse-rate  or  the  pressure  in  the  arteries.  The 
duration  of  the  first  period  varies  inversely  as  the  frequency  of  the 
heart ;  with  the  ordinary  pulse-rate  it  is  the  longest  of  all. 

From  records  taken  in  a  person  with  a  defect  in  the  chest-wall  which 
rendered  the  heart  accessible  the  following  results  were  obtained  as 
to  the  duration  of  the  various  events  of  the  cardiac  cycle :  First  and 
fourth  periods  together,  0-445 ;  third  period,  0-254;  second  period  (pre- 
sphygmic interval),  0-051  second,  the  pulse-rate  being  80  a  minute 
(Tigerstedt).  In  another  case  with  a  similar  defect  the  first  period 
lasted  0-32,  the  fourth  period  (post-sphygmic  interval)  0-06,  the  second 
and  third  periods  together  0-4,  and  the  auricular  systole  o-i  second, 
the  pulse-rate  being  66. 

7 


98  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

The  Auricular  (and  Venous)  Pressure-Curve.— The  fluctuations  of 
pressure  in  the  auricles,  although  confined  within  narrower  hrnits 
than  in  the  ventricles,  are  of  equal  interest.  They  have  been  studied 
in  considerable  detail  both  in  animals  and  by  indirect  methods  iri 
man.  No  fewer  than  three  distinct  elevations  or  '  positive  waves,| 
separated  or  followed  by  three  depressions  or  '  negative  waves,' 
have  been  described  on  the  curve  of  intra-auricular  pressure.  ■ 

The  first  elevation  corresponds  to  the  systole  of  the  auricle.  The 
second  coincides  with  the  onset  of  the  ventricular  systole,  and  is 


Fig.  34. — Schematic  Comparison  of  Pressure  Curves  in  the  Auricle  (or  Superior 
Vena  Cava),  the  Ventricle  and  the  Aorta  in  the  Dog  (Fredericq).  In  the  auricular 
curve  are  to  be  distinguished  ab,  the  first  positive  or  presystolic  wave,  corre- 
sponding to  the  auricular  systole  (a  wave);  bb'  or  be,  second  positive  wave  or 
£rst  systolic  wave,  which  corresponds  with  the  beginning  of  the  ventricular 
systole  (c  wave);  b'cd,  the  steep  negative  wave  of  which  the  beginning  corre- 
sponds to  the  opening  of  the  semilunar  valves;  def,  the  third  positive  wave 
(t)  wave),  more  or  less  serrated,  ending  at/,  the  point  of  opening  of  the  auriculo- 
ventricular  valves;  fg,  a  negative  wave  corresponding  to  the  relaxation  of  the 
ventricle.  The  time  is  indicated  along  the  abscissa  in  tenths  of  a  second,  the 
pressure  along  the  vertical  axis  at  the  left  in  mm.  of  mercury. 

probably  due  to  the  sudden  bulging  of  the  auriculo-ventricular  valve 
into  the  auricle,  or  even  to  a  slight  regurgitation  of  blood  from  the 
ventricle  through  the  valve  before  it  has  completely  closed.  The 
cause  of  the  third  elevation,  which  occurs  during  the  period  occupied 
in  the  ventricular  pressure-curve  by  the  plateau,  is  less  clearly  made 
out.     In  man,  the  events  taking  place  in  the  right  auricle  during  its 


MECHANICS  OF  THE  HEART-BEAT 


99 


systole  can  be  followed  to  some  extent  by  recording  the  venous  pulse 
in  the  jugular  veins,  especially  the  internal  jugular,  at  the  root  of  the 
the  neck  (Fig.  36).  Successful  tracings  can  be  obtained,  not  only  in 
certain  pathological  conditions,  but  in  many  normal  individuals,  and 
it  is  probably  only  a  matter  of  improved  technique  to  obtain  them 
in  all.  The  jugular  venous  pulse-tracing,  like  the  intra-auricular 
pressure-curve,  shows  in  general  three  well-marked  elevations  and 
three  depressions,  and  there  is  good  evidence  that,  broadly  speaking, 
these  features  of  the  jugular  curve  corre- 
spond as  regards  their  origin  with  the 
changes  of  pressure  in  the  auricle. 

Identical  features  are  observed  on  records 
of  the  normal  venous  pulse  taken  from  veins 
of  dogs  near  the  heart,  and  on  records  of  the 
pulse  taken  by  a  sound  in  the  oesophagus. 
The  oesophagus  pulse  is  related  to  the  pul- 
sation of  the  left  auricle,  the  venous  pulse  to 
the  changes  of  pressure  in  the  right  auricle. 
The  first  elevation,  called  the  a  (auricular) 
or  p  (presystolic)  wave,  begins  with,  and  is 
the  result  of,  the  auricular  systole.  It  is 
probably  produced  by  stasis  in  the  veins  due 
to  the  contraction  of  the  auricle,  as  well  as 
to  the  effect  of  the  impact  of  the  auricular 
systole.  The  downstroke  on  the  curve  which 
succeeds  this  first  elevation  corresponds  to 
the  first  negative  wave  or  presystolic  fall, 
which  is  due  to  the  auricular  relaxation .   This 

Fig.  35. — Schema  of  Events  in  the  Cardiac  Cycle, 
in  Relation  to  the  Venous  Pulse  (Ewing).  i,  Tracing 
from  Vena  Cava,  showing  presystolic  rise  and  fall, 
PR.  PF  (a  wave)  ;  SR,  systolic  rise  and  fall 
(c  wave);  O',  first  onflow  wave  and,  DR.  diastolic 
rise  and  fall  (v  wave);  O*.  second  onflow  wave; 
2,  auricular  myogram  (tracing  of  contraction  of 
auricle);  3,  ventricular  myogram  (tracing  of  con- 
traction of  ventricle);  4.  record  of  the  movement 
of  the  auriculo-ventricular  septum;  5.  ventricular 
volume  curve  (plethysmographic  curve  of  dis- 
charge of  the  ventricles) ;  6,  curve  of  aortic  pressure; 
7,  intraventricular  pressure -curve. 

fall  of  pressure  is  terminated  by  a  rise — the  second  positive  wave — which 
begins  at  the  same  moment  as  the  ventricular  systole,  and  is  the  ex- 
pression on  the  venous  pulse-curve  of  that  second  elevation  of  the 
intra-auricular  pressure  whose  probable  cause  has  already  been  found 
in  the  sharp  protrusion  of  the  auriculo-ventricular  valve  into  the 
auricular  cavity  under  the  stress  of  the  ventricular  systole  while  the 
semilunar  valve  are  still  closed.  In  addition  to  the  actual  bulging  of 
the  auriculo-ventricular  valves,  the  impact  of  the  sudden  contraction 
of  the  ventricle  on  its  contents  transmitted  through  the  valve  to 
the  contents  of  the  auricle  may  aid  in  producing  the  rise  of  venous 
pressure.     The  second  elevation  has  been  termed  the  c  wave  by  certain 


loo  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

writers,  who  studied  it  on  jugular  tracings,  because  they  supposed  it 
to  be  simply  transmitted  from  the  pulse  in  the  adjacent  carotid  artery. 
This,  however,  has  been  shown  to  be  erroneous,  although  it  is  true 
enough  that  pulsations  transmitted  from  the  great  arteries  of  the 
thorax  and  neck  may  augment  or  distort  the  second  elevation  of  the 
venous  pulse.  It  has  been  proposed  that  the  second  positive  wave 
should  be  called  the  s  (systolic)  wave.  It  lasts  practically  throughout 
the  presphygmic  period  of  the  ventricular  systole ;  the  opening  of  the 
semilunar  valves,  as  indicated  by  the  appearance  of  the  pulse  in  the 
innominate  artery,  occurs  just  before  the  end  of  the  second  elevation 
(Porter,  Ewing.  etc.).  The  rapid  discharge  of  the  ventricle  through  the 
open  semilunar  valves,  and  its  consequent  diminution  in  size,  especially 
in  its  longitudinal  diameter,  is  associated  with  a  dilatation  of  the 
auricular  cavity  and  a  fall  of  intra-auricular  pressure  which  is  expressed 
on  the  venous  pulse-curve  as  the  downstroke  succeeding  the  second 
positive  wave.  As  the  second  positive  wave  is  termed  the  '  systolic 
rise,'  this  second  negative  wave  may  be  designated  the  systolic  fall  of 
venous  pressure.     About  the  end  of  the  first  third  of  the  ventricular 


Fig.  36. — Simultaneous  Record  of  Jugular  Pulse,  Ventricular  Contraction,  Auricular 
Contraction,  and  Carotid  Pulse  in  Dog  (Cushny  and  Grosh).  a,  c,  v,  the  three 
elevations  ot  the  jugular  pulse.     Time-trace,  fifths  of  a  second. 

systole  the  second  negative  wave  gives  place  to  the  third  positive  wave, 
the  ascent  of  which  is  rather  gradual  owing  to  the  steady  inflow  of 
blood  into  the  auricle  from  the  great  veins,  which  gradually  raises  the 
intra-auricular  pressure.  Towards  the  end  the  rise  is  accentuated  by 
the  return  of  the  base  of  the  ventricle  to  the  position  occupied  by  it  in 
diastole.  According  to  Ewing,  this  third  positive  wave,  the  v  wave 
of  Mackenzie,  really  consists  of  two  waves,  the  first  of  which  he  terms 
the  '  first  onflow  wave  '  or  0  wave,  and  the  second  the  '  diastolic  rise  ' 
or  d  wave.  This  last  is  terminated  by  the  third  negative  wave  or 
diastolic  fall  of  venous  pressure ,  coincident  with  the  re-establishment  of 
a  free  passage  for  the  blood  from  the  auricle  to  the  ventricle  after  the 
relaxation  of  the  latter  and  the  opening  of  the  auriculo-ventricular 
valves. 

Some  difference  of  opinion  exists  as  to  how  the  changes  of  pressure 
in  the  auricle  are  propagated  into  the  veins,  although  there  seems  to 
be  little  reason  to  suppose  that  in  normal  persons  any  actual  re- 
gurgitation of  blood  takes  place.  But  be  this  as  it  may,  the  jugular 
curve,  when  properly  interpreted,  affords  valuable  information  as  to 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      loi 

the  action  of  the  auricle,  information  of  the  same  kind  as  that 
afforded  by  the  arterial  pulse-tracing  and  the  cardiogram  as  to  the 
action  of  the  ventricle.  In  the  interpretation  of  the  venous  pulse- 
tracings,  a  simultaneous  record  of  the  radial  or,  better,  the  carotid 
pulse  or  of  the  apex-beat  is  always  important,  and  often  indispens- 
able, for  it  enables  the  time  of  onset  of  the  ventricular  systole  to  be 
marked  upon  the  phlebogram  (the  venous  trace),  and  this  facihtates 
the  identification  of  the  a  wave,  which  must  immediately  precede, 
and  the  c  or  s  wave,  which  should  coincide  with  the  beginning  of  the 
contraction  of  the  ventricle.  The  student  must,  however,  be  warned 
that  the  proper  interpretation  of  such  tracings  in  the  study  of  cardiac 
disease  is  often  difficult  and  requires  special  knowledge  and  training.* 

Suction  Action  of  the  Ventricle. — We  have  already  said  that  a 
negative  pressure  may  be  detected  in  the  cardiac  cavities  by  means  of 
a  special  lorni  of  mercurial  manometer.  This  is  confirmed  by  an 
examination  of  the  tracings  written  by  good  elastic  manometers,  for 
the  curves  of  both  ventricles  may  often  descend  below  the  line  of 
atmospheric  pressure.  The  cause  of  this  negative  pressure  has  been 
much  discussed.  In  part  it  may  be  ascribed  to  the  aspiration  of  the 
thoracic  cage  when  it  expands  during  inspiration  (p.  225).  But  since 
the  pressure  in  a  vigorously-beating  heart  may  still  become  negative, 
when  the  thorax  has  been  opened,  and  the  influence  of  the  respiratory 
mov^ements  eliminated,  we  must  conclude  that  the  recoil  of  the  some- 
what narrowed,  or  at  least  distorted,  auriculo-ventricular  rings,  and  of 
elastic  structures  in  the  walls  of  the  ventricles,  exerts  of  itself  a  certain 
suction  upon  the  blood.  This,  however,  is  not  an  important  factor  in 
the  maintenance  of  the  circulation. 


Section  III. — Physical  or  Mechanical  Phenomena  of  the 
Circulation  in  the  Bloodvessels. 

The  Arterial  Pulse. — At  each  contracton  of  the  heart  a  quantity  of 
blood,  probably  varying  within  rather  wide  limits  (p.  139),  is  forced 
into  the  already  full  aorta.  If  the  walls  of  the  bloodvessels  were 
rigid,  it  is  evident  (p.  85)  that  exactly  the  same  quantity  would  pass 
at  once  from  the  veins  into  the  right  auricle.  The  work  of  the 
ventricle  would  all  be  spent  within  the  time  of  the  systole,  and  only 
while  blood  was  being  pumped  out  of  the  heart  would  any  enter  it. 
Since,  however,  the  vessels  are  extensible,  some  of  the  blood  forced 
into  the  aorta  during  the  systole  is  heaped  up  in  the  arteries,  beyond 
which,  in  the  narrow  arterioles  and  in  the  capillary  tract,  with  its 
relatively  great  surface,  the  chief  resistance  lies.  The  arteries  are 
accordingly  distended  to  a  greater  extent  than  before  the  systole, 
and,  being  elastic,  they  keep  contracting  upon  their  contents  until 
the  next  systole  over-distends  them  again.  In  this  way,  during  the 
pause,  the  walls  of  the  arteries  are  executing  a  kind  of  elastic  systole, 

*  The  necessary  details  must  be  sought  in  such  works  as  Mackenzie's 
'  Diseases  of  the  Heart,' 


102  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

and  driving  the  blood  on  into  the  capillaries.  The  work  done  by  the 
ventricle  is,  in  fact,  partly  stored  up  as  potential  energy  in  the  tense 
arterial,  wall,  and  this  energy  is  being  continually  transformed  into 
work  upon  the  blood  during  the  pause,  the  heart  continuing,  as  it 
were,  to  contract  by  proxy  during  its  diastole.  Thus,  the  blood 
progresses  along  the  arteries  in  a  series  of  waves,  to  which  the  name 
of  '  blood-waves  '  or  '  pulse-waves  '  may  be  given.     Wherever  the 

1  pulse-wave  spreads  it  manifests  itself  in  various  ways — by  an  increase 
of  blood-pressure,  an  increase  in  the  mean  velocity  of  the  blood-flow, 
an  increase  in  the  volume  of  organs,  and  by  the  visible  and  palpable 
signs  to  which  the  name  of  pulse  is  commonly  given  in  a  restricted 
/  sense.  The  intermittence  in  the  flow  with  which  the  pulse-wave  is 
necessarily  associated  is  at  its  height  at  the  beginning  of  the  aorta. 
In  middle-sized  arteries,  such  as  the  radial,  it  is  still  well  marked,  but 
it  dies  away  as  the  capillaries  are  reached,  and  only  under  special 
conditions  passes  on  into  the  veins,  where,  however,  as  has  just  been 
mentioned,  pulsatory  phenomena  of  a  different  origin  may  be  detected. 
The  pulse  was  well  known  to  the  Greek  physicians,  and  used  by 
them  to  a  certain  extent  as  an  indication  in  practical  medicine. 
Harvey  demonstrated  with  some  clearness  the  relation  of  the  pulse 
to  the  contraction  of  the  heart,  but  Thomas  Young  was  the  first  to 
form  a  proper  conception  of  it  as  the  outward  token  of  a  wave  prop- 
agated from  heart  to  periphery. 

When  the  finger  is  placed  over  a  superficial  artery  like  the  carotid, 
the  radial,  or  the  temporal,  a  throb  or  beat  is  felt,  which,  without 
measurement,  seems  to  be  exactly  coincident  with  the  cardiac 
impulse.  In  certain  situations  the  pulse  can  be  seen  as  a  distinct 
rhjkhmical  rise  and  fall  of  the  skin  over  the  vessel.  The  throbbing 
of  the  carotid,  especially  after  exertion,  is  familiar  to  everyone,  and 
the  beat  of  the  ulnar  artery  can  be  easily  rendered  visible  by  extend- 
ing the  hand  sharply  on  the  wrist.  When  the  pulse  is  felt  by  the 
;  finger,  it  is  not  the  expansion,  but  the  hardening  of  the  wall  of  the 
i  vessel,  due  to  the  increase  of  arterial  pressure,  that  is  perceived;  and 
!  even  a  superficial  artery,  when  embedded  in  soft  tissues  so  that  it 
cannot  be  compressed,  gives  no  token  of  its  presence  to  the  sense  of 
touch.  Sometimes  an  artery  is  longitudinally  extended  by  the 
pulse-wave,  and  this  extension  may  be  far  more  conspicuous  than 
the  lateral  dilatation.  This  is  particularly  seen  when  one  point  of 
the  vessel  is  fixed  and  a  more  distal  point  offers  some  obstruction  to 
the  blood-flow,  as  at  a  bifurcation  or  in  an  artery  which  has  been 
hgatured  and  divided. 

By  means  of  the  sphygmograph,  the  lateral  movements  of  the 
arterial  wall,  or,  rather,  in  man,  the  movements  of  the  skin  and  other 
tissues  lying  over  the  bloodvessel,  can  be  magnified  and  recorded. 

It  would  be  very  unprofitable  to  enumerate  all  the  sphygmographs 
which  ingenuity  has  invented  and  found  names  for.     The  first  attempt 


MECHANICS  OF  THE  CIRCULATION  IN  THE    VESSELS       103 


I'ig-  37- — Scheme  of  Marey's  Sphygmo- 
graph.  A,  toothed  wheel  connected  with 
axle  H.  and  gearing  into  toothed  upright 
B;  C.  ivory  pad  which  rests  over  blood- 
vessel and  is  pressed  on  it  by  moving  G. 
a  screw  passing  through  the  spring  J ; 
E.  writing-lever  attached  to  axle  H,  and 
moved  by  its  rotation.  E  writes  on  D.  a 
travelling  surface  moved  by  cloclavork  F. 


to  magnify  the  movements  of  the  pulse  was  made  by  loosely  attaching 

a  thin  fibre  of  glass  or  wax  to  the  skin  with  a  little  iard,  in  order  to 

demonstrate  the  venous  pulse  which  appears  under  certain  conditions. 

In  all  modem  sphygmographs  there  is  a  part,  usually  button-shaped, 

which  is  pressed  over  the  artery  by  means  of  a  spring,  as  in  Marey's 

and   Dudgeon's  sphj^gmographs, 

or  by  a  weight,  or  by  a  column  of 

liquid.     In  Marey's   instrument, 

the  button  acts  upon  a  toothed 

rod  gearing  into  a  toothed  wheel, 

to  which  a  lever,  or  a  system  of 

levers,  is  attached.    The  lever  has 

a  writing-point  which  records  the 

movement  on  a  smoked  plate,  or 

a    plate    covered    with   smoked 

paper,  drawn  uniformly  along  by 

cloclcwork  (Figs.  37,  100).  Special 

forms  of  sphygmographs  (poly- 
graphs) have  been  devised,  which, 

by  the  addition  of  one  or  more 

recording  tambours,   permit  the 

simultaneous  record  of  movements  from  two  or  more  points  of  the 

vascular  system — for  example,  the  radial  artery  and  the  jugular  vein, 

or  the  radial  or  carotid  artery,  jugular  vein,  and  the  apex  of  the  heart. 

In  rare  cases,  with  de- 
fect of  the  chest  wall, 
a  tracing  may  be  ob- 
tained even  from  the 
aorta  (Fig.  40). 

In  a  normal  arterial 
pulse-tracing  (Fig.  38) 
the  ascent  or  ana- 
crotic limb  is  abrupt 
and  unbroken ;  the 
descent  or  katacrotic 
limb  is  more  gradual, 
and  is  interrupted  by 
one,  two,  or  even 
three  or  more,  second- 
ary wavelets.  The 
most  important  and 
constant  of  these  is 
the  one  marked  3, 
which  has  received  the 
name  of  the  dicrotic 
wave.  Usually  less 
marked,  and  some- 
times absent,    is  the 


Fig.  38. — Pulse-Tracings,  i,  primary  elevation ;  2,  predi- 
crotic  or  first  tidal  wave  ;  3,  dicrotic  wave.  The 
depression  between  2  and  3  is  the  dicrotic  or  aortic 
notch;  3  is  better  marked  in  B  than  in  A.  C.  dicrotic 
pulse  with  low  arterial  pressure;  D,  pulse  with  high 
arterial  pressure — smnmit  of  primary  elevation  in  the 
form  of  an  ascending  plateau.  E,  systolic  anacrotic 
pulse;  the  secondary  wavelet  a  occurs  during  the 
upstroke  corresponding  to  the  ventricular  systole. 
F,  presystolic  anacrotic  pulse;  a  occurs  just  before 
the  systole  of  the  ventricle.  In  this  rarer  form  of 
anacrotism,  a  may  sometimes  be  due  to  the  auricular 
systole  when  the  aortic  valves  are  incompetent. 


wavelet  2  between  the  dicrotic  elevation  and  the  apex  of  the  curve. 
It  is  generally  termed  the  predicrotic  wave.  Oscillations,  due  to 
vibrations    of    the   recording   apparatus,  appear  on   many  pulse- 


I04 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


Fig.  39.  —  Pulse  -  Tracings 
from  Different  Arteries 
(v.  Frey).  T,  temporal; 
R.  radial ;  P,  artery  of  foot. 


tracings,  and  it  is  important  to  recognize  their  cause,  so  that  no 
weight  may  be  given  to  them. 

In  the  explanation  of  the  pulse-tracing,  a  fundamental  fact  to  be 
borne  in  mind  is  the  elasticity  of  the  vessels.     When  an  incompres- 
sible fluid  like  water  is  injected  by  an  intermittent  pump  into  one  end 
of  an  elastic  tube  a  wa\e  is  set  up,  which  is  transmitted  to  the  other 
end  of  the  tube.     It  is  a  positive  wave — that 
is,  it  causes  an  increase  of  pressure  and  an 
expansion  of   the   tube  wherever  it  arrives; 
and  if  a  series  of  levers  be  placed  in  contact 
with   the    tube,    they  will   rise  and   sink    in 
succession  as  the  wave  passes  them.     After 
the  passage  of  this  primary  wave  the  walls  of 
'  the  tube,  instead  of  coming  instantly  to  rest 
in  their  original  position,  regain  it  by  a  series 
of  oscillations,  first  shrinking  too  much,  then 
expanding  too  much,  but  at  each  movement 
coming  nearer  to  the  position  of  equiubrium. 
Each  vibration  of  the  elastic  wall  is  of  course 
accompanied  by  a  change  of  pressure  in  the 
contents  of  the  tube.     This  change  of  pressure 
runs  along  the  tube  as   a   wave;    and    such 
waves,  succeeding  the  primarj-  one,  may  be 
called  secondary  waves  of  oscillation.     These 
secondary  waves  will  be  set  up  in  an  elastic 
system  whether  the  distal  end  of  the  system 
be  closed  or  open.     But  if  it  is  closed,   or 
sufficiently  obstructed   without   being   actu- 
ally closed,  secondary  waves  of  another  kind  may  also  be  generated, 
I  the  primary  wave  on  arriving  at  the  distal  end  being  reflected  there. 
I  The  reflected  wave  running  back  towards  the  central  end  may  there 
1  again  undergo  reflexion,  and  pass  out  once  more  towards  the  distal  end 
las  a  centrifugal,  twice-reflected  wave.     When  the  liquid  ceases  to  enter 
jthe  tube  at  the  end  of  the  stroke,  a  wave  of  diminished  pressure — a 
negative  wave — is  generated  at  the  central 
lend,  and  is  propagated  to  the  distal  end, 
fwhere  it  may  be  reflected  just  like  the  posi- 
tive wave. 

Although  under  certain  conditions  the 
dicrotic  wave  is  so  marked  that  the  double 
beat  of  the  pulse  was  discovered  and 
named  by  physicians  long  before  the  in- 
vention of  any  sphygmograph,  perhaps 
no  physiological  question  has  been  more 
'discussed  or  is  less  understood  than  the 
mechanism  of  its  production.  Two 
points,  however,  seem  to  be  clear :  (i)  That 
it  is  a  centrifugal,  and  not  a  centripetal,  wave — that  is  to  say,  it 
travels  away  from,  and  not  towards,  the  heart ;  (2)  that  the  aortic 
semilunar  valves  have  something  to  do  with  its  origin. 

It  is  not  a  centripetal  wave,  for  in  tracings  taken  at  all  parts  of  the 
arterial  path,  no  matter  what  the  distance  from  the  heart  and  the 


Fig.  40.  —  Pulse-Curve  from 
Human  Aorta  (after  Tiger- 
stedt). 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      105 

capillaries  {e.g.,  the  origin  of  the  carotid  and  the  radial  at  the  wrist),! 
the  dicrotic  wave  is  separated  by  the  same  interval  from  the  begin- 1 
ning  of  the  primary  elevation.  This  can  only  be  explained  by 
supposing  that  it  has  the  same  point  of  origin,  and  travels  with  the 
same  velocity  and  in  the  same  direction  as  the  primary  wave.  It  is 
not,  then,  a  wave  reflected  directly  from  the  peripheral  distribution 
of  the  artery  from  which  the  pulse-tracing  is  taken. 

Some  writers  have  contended  that  it  is  a  centrifugal  twice-reflected 
wave,  and,  indeed,  traces  of  such  waves  may  be  detected  in  the  vessels 
of  newly-killed  animals  when  changes  of  pressure  of  the  same  order 
of  magnitude  as  the  arterial  pulse  are  artificially  produced  by  a  pump 
and  recorded  by  elastic  manometers  connected  with  the  interior  of 
an  artery.  It  has  been  supposed  that  these  secondary  waves  are 
reflected  first  from  peripheral  points  at  which  the  blood-flow  is  particu- 
larly obstructed  (the  bifurcations  of  the  larger  arteries,  and  the  small 
arteries  and  capillaries  in  general),  and  that,  running  towards  the  heart, 
they  are  again  reflected  outwards  from  the  semilunar  valves.  It  has 
been  urged  in  support  of  this  view  that  in  very  small  animals  (guinea- 
pigs)  no  dicrotic  elevation  occurs  on  the  pulse-tracing,  since  the  path 
which  the  reflected  wave  has  to  follow  is  so  short  that  it  arrives  at  the 
root  of  the  aorta  before  the  primary  elevation  is  over.  But  this 
argument  is  by  no  means  conclusive,  and,  indeed,  the  great  difference 
in  the  distance  from  the  heart  of  the  numerous  points  at  which  reflection 
must  take  place  is  one  of  the  chief  difficulties  of  the  hypothesis.  For 
it  is  not  easy  to  understand  how  the  reflected  fragments  of  the  primary 
wave,  arriving  at  different  intervals  at  the  heart,  can  be  integrated  into 
the  single  considerable  dicrotic  elevation. 

The  explanation  that  best  takes  account  of  the  facts  and  renders 
most  clear  the  role  of  the  semilunar  valves  is  somewhat  as  follows: 
When  the  systole  abruptly  comes  to  an  end  and  the  outflow  from  the 
ventricle  ceases,  the  column  of  blood  in  the  aorta  tends  still  to  move 
on  in  virtue  of  its  inertia,  and  a  diminution  of  pressure,  accom- 
panied by  a  corresponding  contraction  of  the  aorta,  takes  .place 
behind  it,  just  as  a  negative  wave  is  set  up  in  the  central  end  of  the 
elastic  tube  when  the  stroke  of  the  pump  is  over.  At  the  same 
moment,  and  while  the  semilunar  valves  are  still  for  an  instant  in- 
completely closed,  the  diminution  of  pressure  in  the  beginning  of  the 
aorta  is  intensihed  by  the  aspiration  of  the  relaxing  ventricle,  which 
sucks  the  blood  back  against  the  valves,  and  draws  them  a  little  way 
into  its  cavity.  A  negative  wave,  therefore — a  wave  of  diminished 
pressure,  represented  in  the  pulse-curve  by  the  '  aortic  notch  ' — 
travels  out  towards  the  periphery.  The  diminution  of  pressure  is 
quickly  followed  by  a  rebound,  as  always  happens  in  an  elastic 
system.  The  recoiling  blood  meets  the  closed  semilunar  valves. 
The  aorta  expands  again,  and  the  expansion  is  propagated  once  more 
along  the  arteries  as  the  dicrotic  elevation.  It  is  possible  that  this 
elevation  may  be  reinforced  by  a  reflected  wave  produced  in  the 
manner  described. 


io6  THE  ClhCULATION  OF  THE  BLOOD  AND  LYMPH 

When  the  semilunar  valve  becomes  incompetent  in  disease,  or  is 
rendered  insufficient  in  animals  by  the  artificial  rupture  of  one  or 
more  of  its  segments,  the  dicrotic  wave,  as  will  be  readily  understood 
from  the  manner  in  which  it  is  produced,  either  disappears  altogether 
or  is  markedly  enfeebled.  But  apart  from  any  anatomical  lesion  or 
functional  defect  in  the  aortic  valves,  the  prominence  of  the  wave 
varies  with  a  great  number  of  circumstances,  some  of  which  are  in  a 

I  measure  understood,  while  others  remain  obscure.  It  varies  in  par- 
ticular with  the  abruptness  of  discharge  of  the  ventricle  and  the  ex- 
tensibility of  the  arteries.  The  conditions  are  usually  favourable  when 
the  arterial  pressure  is  low,  for  the  blood  then  passes  quickly  from  the 
ventricle  into  the  arteries,  which,  already  only  moderately  tense,  are 
easily  dilated  by  the  primary  wave,  then  sharply  collapse,  and  are  again 
abruptly  distended  when  the  dicrotic  wave  arrives.  And,  in  fact,  an 
exaggeration  of  the  dicrotic  wavelet  may  be  artificially  produced  by 
[  nitrite  of  amyl  (Fig.  102,  p.  207),  a  drug  which  lessens  the  blood-pressure 
I  by  dilating  the  small  arteries.  Muscular  exercise  (Fig.  loi,  p.  207), 
running  or  bicycling,  for  instance,  has  a  similar  effect  on  the  sphygmo- 
gram,  although  the  explanation  can  scarcely  be  the  same,  since  the  blood- 
pressure  mounts  rapidly  when  moderate  exercise  begins,  and  only 
gradually  falls  during  its  continuance,  with  an  abrupt  decline  to  normal 
or  below  it  on  cessation  of  work  (Bowen).  The  increase  in  the  pulse- 
rate  may  have  something  to  do  in  this  case  with  the  exaggeration  of  the 
dicrotism,  which  is  very  frequently,  although  by  no  means  invariably, 
associated  with  a  rapidly-beating  heart,  and  therefore  is  often  seen  in 
fever.  On  the  other  hand,  in  certain  diseases  associated  with  a  high 
arterial  pressure,  the  dicrotic  elevation  almost  disappears.  Ather- 
omatous arteries,  being  very  inextensible,  do  not  allow  a  dicrotic  pulse. 
Since  the  pulse  represents  a  periodical  increase  and  diminution  in 
the  amount  of  distension  of  an  artery  at  any  point,  the  line  joining 
all  the  minima  of  the  pulse-curve  will  vary  in  its  height  above  the 
base-line,  or  line  of  no  pressure,  according  to  the  amount  of  permanent 
distension,  i.e.,  permanent  blood-pressure,  which  the  heart  in  any  given 
circumstances  is  able  to  maintain.  Any  circumstance  that  tends  to 
lessen  the  permanent  distension  will  cause  a  fall  of  the  line  of  minima, 
and  any  circumstance  tending  to  increase  the  distension  will  cause  that 
line  to  rise.  If,  for  example,  the  arm  be  raised  while  a  pulse-tracing 
is  being  taken  from  the  wrist,  the  line  of  minima  falls  because  the 
permanent  pressure  in  the  radial  artery  is  diminished. 

The  form  of  the  pulse-curve  varies  in  the  different  arteries,  and 
therefore  in  making  comparisons  the  same  artery  should  be  used. 
When  the  wave  of  blood  only  enters  an  artery  slowly,  the  ascending 
part  of  the  curve  will  be  oblique.  This  is  normally  the  case  in  a 
pulse-curve  of  a  distant  artery,  such  as  the  posterior  tibial.  The 
height  of  the  wave  is  also  less  than  in  an  artery  nearer  the  heart,  such 
as  the  carotid,  or  even  the  axillary,  where  the  primary  elevation  is 
relatively  abrupt  (Fig.  39,  p.  104). 

Anacrotic  Pulse. — As  a  rule,  the  ascent  of  the  tracing  is  unbroken 
by  secondary  waves,  but  in  certain  circumstances  these  may  appear 
on  it.  This  condition,  which,  when  well  marked  at  any  rate,  may 
be  considered  pathological,  is  called  anacrotism  (Fig.  38).  It  is  seen 
when  the  discharge  of  the  left  ventricle  into  the  aorta  is  slow  and 
difficult — e.g.,  in  cases  where  the  orifice  of  the  aorta  has  been 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS       107 

narrowed  from  disease  of  the  semilunar  valves  (aortic  stenosis). 
Since  this  condition  is  associated  with  hypertrophy  and  dilatation 
of  the  left  ventricle,  the  slow  emptying  of  the  ventricle  is  partly  due 
to  the  greater  quantity  of  blood  which  it  contains.  In  whatever 
way  the  delay  in  the  emptying  of  the  ventricle  is  brought  about,  the 
most  probable  explanation  of  the  anacrotic  pulse  is  that  the  delay 
affords  time  for  one  or  more  secondary  waves  to  be  developed  in  the 
arterial  system  before  the  summit  of  the  curve  has  been  reached,  and 
that  these  are  superposed  upon  the  long-drawn  primary  elevation. 
In  aortic  insufficiency,  where  the  left  side  of  the  heart  is  never  cut  off 
entirely  from  the  aorta,  the  auricular  impulse  is  sometimes  marked 
on  the  pulse-curve  as  a  distinct  elevation;  and  this  gives  rise  to  a 
peculiar  kind  of  anacrotic  pulse,  especially  in  the  arteries  nearest  the 
heart  (Fig.  38,  F,  p.  103). 

Frequency  of  the  Pulse. — In  health,  the  working  of  the  cardiac 
pump  is  so  smooth  and  apparently  so  self-directed  that  it  needs  a 
certain  degree  of  attention  to  perceive  that  the  rate  of  the  stroke  is 
not  absolutely  constant.  It  is,  in  reaUty,  affected  by  many  internal 
conditions  and  external  influences. 

At  the  end  of  foetal  life  the  rate  is  given  as  144  to  133;  from  birth 
till  the  end  of  the  first  year,  140  to  123 ;  from  10  to  15  years,  91  to  76 ; 
from  20  to  25  years,  73  to  69.  It  remains  at  this  till  60  years,  and 
increases  again  somewhat  in  old  age.*  At  all  ages  the  pulse  is  some- 
what quicker  in  the  female  than  in  the  male,  the  excess  amounting  to 
about  8  beats  a  minute.  So  that  if  we  take  the  average  rate  for  a 
man  (in  the  sitting  position)  as  72,  the  average  for  a  woman  will  be 
80.  The  difference  is  partly  due  to  the  fact  that  the  average  man 
is  taller  than  the  average  woman;  and  it  is  known  that  in  persons  of 
the  same  sex  and  age  the  pulse-rate  has  an  inverse  relation  to  the 
stature.  But  there  may  be,  in  addition,  a  real  sexual  difference. 
It  must  not  be  forgotten  that  a  certain  number  of  perfectly  healthy 
persons,  who  may  even  be  noted  for  their  powers  of  physical  en- 
durance, have  an  habitually  slow  pulse,  not  above  50  in  the  minute. 
The  position  of  the  body  exercises  a  slight,  but  relatively  constant, 
influence  on  the  rate,  which  is  greater  in  the  standing  than  in  the 
sitting  posture,  and  greater  in  the  latter  than  in  the  recumbent 
position.  And  this  is  true  even  when  muscular  action  is  as  far  as 
possible  eliminated  by  fastening  the  person  to  a  board.     The  pulse 

*  It  must  be  remembered  that  these  numbers  are  merely  averages.  Some 
healthy  individuals  have  a  much  lower  pulse-rate  than  72  per  minute,  and 
some  a  rate  considerably  greater.  Thus,  while  the  average  pulse-rate  (taken 
in  the  sitting  position)  of  87  healthy  (male)  students,  whose  ages  ranged  from 
18  to  36  years,  was  73,  the  extreme  variation  was  from  54  to  89.  In  the 
standing  position  the  average  was  80,  and  the  variations  64  to  105.  In 
the  supine  position,  average  69,  and  variations  48  to  98.  After  a  short  spell 
of  muscular  exercise  (generally  running  up  and  down  some  flights  of  stairs) 
the  average  in  the  standing  position  was  119,  the  variations  75  to  164.  and 
the  average  increase  32. 


io8  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

is  further  affected  by  the  respiratory  movements,  especially  when 
they  are  exaggerated  in  forced  breathing,  being  accelerated  during 
each  inspiration  (p.  287).  It  is  also  increased  by  the  taking  of  food, 
and  especially  of  alcoholic  stimulants,  by  muscular  exercise,  in  fever 
and  many  other  pathological  conditions,  and  by  a  high  external 
temperature.  A  warm  bath,  for  example,  causes  a  very  distinct 
acceleration  of  the  heart;  and  Delaroche  found  that  in  air  at  the 
temperature  of  65°  C  his  pulse  went  up  to  160.  A  cold  bath  may 
depress  the  pulse-rate  to  60,  or  even  less.  During  sleep  it  may  fall 
to  50.  It  is  greatly  influenced  by  psychical  events,  and  that  in  the 
direction  either  of  an  increase  or  a  decrease.  Finally,  it  ought  to  be 
remembered  as  of  some  practical  importance  that  the  pulse-rate  in 
women  and  children,  but  particularly  in  the  latter,  is  less  steady 
than  in  men,  and  more  apt  to  be  affected  by  trivial  causes.  And  it 
is  a  good  general  rule  to  let  a  short  interval  elapse  after  the  finger  is 
laid  on  the  artery  before  beginning  to  count  the  pulse,  so  that  the 
acceleration  due  to  the  agitation  of  the  patient  may  have  time  to 
subside. 

Rate  of  Propagation  of  the  Pulse-Wave. — When  pulse-tracings  are 
taken  simultaneously  at  two  points  of  the  arterial  system  unequally 
distant  from  the  heart,  by  two  sphygmographs  whose  writing-points 
move  in  the  same  vertical  straight  line,  it  is  found  that  the  ascent 
of  the  curve  begins  later  at  the  more  distant  than  at  the  nearer  point. 
Since  waves  like  the  pulse- wave  travel  with  approximately  the  same 
velocity  in  different  parts  of  an  elastic  system  like  the  arterial '  tree,' 
this  '  delay  '  must  be  due  to  the  difference  in  the  length  of  the  two 
paths.  The  difference  in  length  can  be  measured;  the  time- value  of 
the  '  delay  '  can  be  deduced  from  the  rate  of  movement  of  the  re- 
cording surface;  dividing  the  length  by  the  time,  we  arrive  at  the 
rate  of  propagation  of  the  pulse-wave.  The  average  rate  has  been 
found  to  be  about  7  metres  per  second  in  man  in  the  arteries  of  the 
upper  limb,  and  8  metres  in  those  of  the  lower  limb,  the  difference 
being  due  to  the  smaller  distensibihty  of  the  latter.  In  sleep  the 
velocity  diminishes  almost  a  metre  a  second.  It  increases  in  arterio- 
sclerosis, where  the  distensibility  of  the  arteries  is  diminished,  and 
in  chronic  nephritis  with  hypertrophy  of  the  heart,  in  which  the 
blood-pressure  is  increased.  The  mean  velocity  of  the  pulse- wave 
is  about  the  same  as  the  speed  of  a  moderately  fast  steamship  (say, 
17  miles  an  hour),  but  less  than  that  of  a  wave  of  the  sea  in  a  strong 
gale.  The  velocity  of  the  pulse-wave  must  not  be  confounded  with 
that  of  the  blood-stream  itself,  which  is  not  one-thirtieth  as  great. 
A  ripple  passes  over  the  surface  of  a  river  at  its  own  rate — a  rate 
that  is  independent  of  the  velocity  of  the  current.  The  passage  of 
the  ripple  is  not  a  bodily  transference  of  the  particles  of  water  of 
which  at  any  given  moment  the  wave  is  composed,  but  the  propaga- 
tion of  a  change  of  relative  position  of  the  particles.     The  mere  fact 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      109 

that  the  ripple  can  pass  upstream  as  well  as  down  is  sufficient  to 
illustrate  this.  The  pulse- wave  does  not,  however,  correspond  in 
every  respect  to  a  ripple  on  a  stream,  for  the  bodily  transfer  of  the 
blood  depends  upon  the  series  of  blood- waves  which  the  heart  sets 
travelUng  along  the  arteries.  Every  particle  of  blood  is  advanced, 
on  the  whole,  by  a  certain  distance  with  every  pulse-wave  in  which 
for  the  time  it  takes  its  place.  But  no  particle  continues  in  the 
front  of  the  pulse-wave  from  beginning  to  end  of  the  arterial  system. 
The  '  delay  '  or  '  retardation  '  of  the  pulse  (the  interval,  say,  between 
the  beginning  of  the  ascent  of  the  carotid  and  radial  curves)  is 
practically  constant  in  the  same  individual,  not  only  in  health,  but 
also  in  most  diseases.  But  the  retardation  is  markedly  increased 
when  the  pulse-wave  has  to  pass  through  a  portion  of  an  artery 
whose  lumen  is  either  greatly  widened  (in  aneurism)  or  greatly 
constricted  (in  endarteritis  obliterans). 

The  Blood- Pressure  Pulse  in  the  Arteries. — In  man  it  is  only 
possible  to  trace  the  pulse- wave  along  the  arteries  by  movements  of 
the  walls  of  the  vessels  transmitted  through  the  overlying  tissues. 
In  animals  the  changes  of  pressure  that  occu*"  in  the  blood  itself  can 
be  directly  registered,  and  these  changes  may  be  spoken  of  as  the 
blood-pressure  pulse.  At  bottom,  as  already  pointed  out,  the 
phenomenon  is  exactly  the  same  as  that  we  have  been  dealing  with 
in  our  study  of  the  external  pulse.  We  are  only  now  to  follow,  by 
a  more  direct,  and  in  some  respects  a  more  perfect  method,  the  same 
wave  of  blood  along  the  same  channel. 

Measurement  of  the  Arterial  Blood-Pressure. — Hales  was  the  first  to 
measure  the  blood-pressure.  This  he  did  by  connecting  a  tall  glass 
tube  with  the  crural  artery  of  a  horse.  The  height  to  which  the  blood 
rose  in  the  tube  indicated  the  pressure  in  the  vessel.  Poiseuille,  nearly 
half  a  century  later,  applied  the  mercury  manometer,  which  had  already 
been  used  in  physics,  to  the  measurement  of  blood-pressure.  Ludwig 
and  others  improved  this  method  by  making  the  manometer  self- 
registering  by  means  of  a  float  in  the  open  limb,  supporting  a  style 
which  writes  on  a  revolving  drum,  or  kymograph.  (For  the  method 
of  taking  a  blood-pressure  tracing,  see  p.  208.) 

For  reasons  already  mentioned,  the  mercurial  manometer  is  better 
suited  for  measuring  the  mean  blood-pressure,  or  for  recording  changes 
in  the  pressure  which  last  for  some  time,  than  for  following  the  rapid 
variations  of  the  pulse-wave.  For  the  latter  purpose,  one  of  the  class 
of  elastic  manometers  is  required  (p.  93). 

A  blood-pressure  tracing  taken  from  an  artery  with  a  manometer 
of  this  sort  yields  the  truest  picture  of  the  pulse-wave  which  it  is 
possible  to  obtain,  because  the  reproduction  of  it  is  the  most  direct. 
The  fact  that  such  a  tracing  shows  a  close  agreement  with  the  trace 
of  a  good  sphygmograph  properly  applied  to  the  corresponding  artery 
on  the  other  side  is  a  striking  proof  of  the  general  accuracy  of  the 
sphygmographic  method  for  physiological  purposes,  and  enables  us  to 
guide  ourselves  in  transferring  to  man,  in  whom,  of  course,  the  sphyg- 
mograph can  alone  be  used,  the  information  derived  from  direct 
manometric  observations  in  animcds. 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


For  the  same  reason  it  is  unnecessary  to  discuss  the  manometric 
tracings,  as  regards  the  pulsatory  phenomena,  in  all  their  details. 
It  will  be  sufficient  to  say  that,  while  the  form  of  the  blood-pressure 
pulse-curve  varies  with  the  mean  blood-pressure,  the  dicrotic  wave 
is  always  marked  on  it,  preceded  by  one  or  more  oscillations  falling 
within  the  period  of  the  systole,  and  followed  by  one  or  more  within 
the  period  of  the  diastole.  When  the  blood-pressure  is  low,  the  first 
or  primary  elevation  is  the  highest  of  the  whole  curve  (Fig.  42).  When 
the  blood-pressure  is  high,  the  maximum  falls  later  coinciding  with 

one  of  the  secondary 
systolic  waves,  but 
always  preceding  the 
dicrotic  wave;  and  the 
curve  assumes  an  ana- 
crotic character. 

That  all  the  secondary 
oscillations,  including  the 
dicrotic  wavelet,  are  cen- 
trifugal, and  not  centrip- 
etal, may  be  shown,  just 
as  in  the  sphygmographic 
method,  by  recording  the 
blood-pressure  simultane- 
ously at  two  points  of  the 
arterial  system  at  differ- 
ent distances  from  the 
heart — e.g.,  in  the  crural 
and  carotid  arteries.  The 
secondary  waves  are 
found,  by  measuring  the 
tracings,  to  reach  the 
more  distal  point  later 
than  the  more  central. 

The  increase  of  pres- 
sure during  the  systole, 
as  indicated  by  the  height 
of  the  primary  elevation, 
is  always  very  large,  much 
larger  than  it  appears  in  a 
tracing  taken  with  a  mer- 
cury manometer.  In  the 
rabbit  this  pulsatory  variation  is  one-third  to  one-fourth  of  the  minimum 
pressure.  In  the  dog  it  is  still  greater,  owing  to  the  slower  rate  of  the 
heart,  and  often  amounts  to  50  mm.  of  mercury,  while  under  favourable 
conditions  (low  minimum  pressure  and  slowly  -  beating  heart)  the 
systolic  increase  of  pressure  may  be  actually  more  than  double  the 
minimum  (Hiirthle).  Fick  found  also,  by  means  of  his  spring  man- 
ometer, that  the  pulsatory  variations  of  blood-pressure  were  greater 
than  the  respiratory  variations  (p.  283),  although  in  the  records  of 
the  mercury  manometer  the  reverse  appears  often  to  be  the  case. 
Landois,  too,  in  the  course  of  experiments  in  which  a  divided  artery 
was  allowed  to  spout  against  a  moving  surface,  and  to  trace  on  it  a 
sort  of  pulse-curve  painted  in  blood  (a  ha;mautogram  as  it  is  called). 


Fig.  41. — Arrangement  for  taking  a  Blood-Pressure 
Tracing.  M,  manometer;  Hg,  mercury;  F,  float 
armed  with  writing-point ;  A,  thread  attached  to 
a  wire  projecting  from  the  drum  and  supporting 
a  small  weight.  The  thread  keeps  the  writing- 
point  in  contact  with  the  smoked  paper  on  the 
drum.  B  is  a  strong  rubber  tube  connecting  the 
manometer  with  the  artery;  C,  a  pinchcock  on 
the  rubber  tube,  which  is  taken  off  when  a  tracing 
is  to  be  obtained. 


MECHANICS  OF  THE  CIRCULATION  IN  THE  VESSELS      iii 


observed  -that  the  rate  of  escape  of  the  blood  was  nearly  50  per  cent, 
greater  during  the  systole  than  during  the  pause  of  the  heart.  The 
existence  of  tlie  dicrotic  wave  on  this  tracing  was  long  looked  on  as  the 
best  proof  that  it  was  not  an  artificial  phenomenon. 

The  wave  of  increased  pres- 
sure, as  it  runs  along  the  arterial 
system,  carries  with  it  wherever 
it  arrives  an  increase  of  potential 
energy.  But  this  excess  of  po- 
tential energy  is  continually  being 
worn  down,  owing  to  the  friction 
of  the  vascular  bed ;  and  although 
in  the  comparatively  large  arteries 
the  loss  of  energy  is  not  great,  it 
rapidly  increases  as  the  arteries 
approach  their  termination,  and 
begin  to  break  up  into  the  narrow 
arterioles  which  feed  the  capillary 
network.  For  not  only  is  the  ratio 
of  the  total  surface  to  the  total 
cross-section,  and  therefore  the 
friction,  increased  with  every 
bifurcation,  but  the  mere  change 
of  direction  and  division  of  the 
wave  cannot  take  place  without 
loss  of  energy.  For  this  reason 
the  fluctuations  of  blood-pres- 
sure are  greater  in  the  large  arteries  near  the  heart  than  in  arteries 
smaller  and  more  remote.  In  the  wide  and  much-branched  capillary 
bed  the  pulse-wave  disappears  altogether,  and  the  blood-pressure 
becomes  relatively  constant  or  permanent.     And  it  is  for  some 

purposes  convenient  to  look  upon 
the  blood-pressure  in  the  arteries  as 
made  up  of  a  permanent  element, 
with  pulsatory  oscillations  super- 
posed on  it.  Since  no  portion  of  the 
arterial  system  is  more  than  partially 
emptied  in  the  interval  between  two 
blood-waves,  the  minimum  or  per- 
manent pressure  is  always  positive 
— i.e.,  always  above  that  of  the  atmosphere,  the  beats  of  the  heart 
succeeding  each  other  so  rapidly  that  the  successive  waves  over- 
lap or  '  interfere,'  and  are  only  separated  at  their  crests. 

If  the  heart  is  stopped  while  a  blood-pressure  tracing  is  being 
taken — and  we  shall  sec  later  on  how  this  can  be  done  (p.  157) — the 
minimum  hne  of  the  tracing  goes  on  falhng  towards  the  zero-Une. 


Fig.  42. — Curves  of  Blood-Pressure  taken 
with  a  Spring  Manometer  from  the 
Carotid  Artery  of  a  Dog  (Hvirthle). 
When  I  was  taken  the  blood-pressare 
was  high;  2  corresponds  to  a  medium. 
3  to  a  low,  and  4  to  a  very  low,  blood- 
pressure;  p  is  the  primary  elevation 
— this  and  the  succeeding  elevations 
between  p  and  a  are  called  systolic 
waves;  the  systolic  waves  are  followed 
by  a  marked  elevation  d,  which  corre- 
sponds to  the  dicrotic  wave. 


Fig.  43.  —  Blood  -  Pressure  Tracing. 
The  horizontal  straight  line  inter- 
secting the  curves  is  the  line  of 
mean  pressure. 


112  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

When  the  heart  begins  beating  again,  the  pressure-curve  rises,  not 
by  a  continuous  ascent,  but  by  successive  leaps,  each  corresponding 
to  a  beat  of  the  heart,  and  each  overtopping  its  predecessor,  till  the 
old  line  of  minimum  or  of  mean  pressure  is  again  reached. 

The  mean  arterial  blood-pressure  is  the  permanent  pressure  plus 
one-half  of  the  average  pulsatory  oscillation.  In  a  blood-pressure 
tracing  the  line  of  permanent  pressure  joins  all  the  minima;  the  line 
of  maximum  pressure  joins  all  the  maxima ;  the  line  of  mean  pressure 
is  drawn  between  them  in  such  a  way  that,  of  the  area  included 
between  it  and  the  blood-pressure  curve,  as  much  lies  above  as  below 
it  (Fig.  43).  As  has  been  said,  a  tracing  taken  with  a  mercury  man- 
ometer gives  approximately  the  mean  blood-pressure.  Each  beat  of 
the  heart  is  represented  on  it  by  a  single  elevation  of  variable  size, 
sometimes  not  amounting  to  more  than  one-twentieth  of  the  height 
of  the  curve  above  the  line  of  zero  or  atmospheric  pressure,  but  some- 
times much  larger.  The  oscillations  due  to  the  heart-beat  are 
superposed  upon  much  longer,  and  often,  as  registered  in  this  way, 
larger  waves,  caused  by  the  movements  of  respiration.  So  much 
having  been  said  by  way  of  definition,  we  have  now  to  consider  the 
amount  of  the  mean  arterial  pressure,  the  variations  which  it  under- 
goes, and  the  factors  on  which  its  maintenance  depends. 

As  to  its  amount,  it  will  be  sufficiently  accurate  to  say  that  in  the 
systemic  arteries  of  warm-blooded  animals  in  general  (including 
birds),  and  of  man  in  particular,  the  mean  pressure  does  not,  under 
ordinary  conditions,  descend  much  below  100  mm.  of  mercury,  nor 
rise  much  above  200  mm. ;  while  in  cold-blooded  animals  it  seldom 
exceeds  50  mm.,  and  may  fall  as  low  as  20  mm. 

It  does  not  seem  possible,  at  least  with  our  present  data,  to  further 
subdivide  these  two  great  groups;  nor  do  we  know  precisely  whether 
the  distinction  depends  mainly  on  morphological  or  mainly  on  physio- 
logical differences,  whether,  that  is  to  say,  the  warm-blooded  animal 
has  a  higher  blood-pressure  than  the  cold-blooded  chiefly  because  its 
vascular  system  (and  especially  its  heart)  is  anatomically  more  perfect, 
or  because  its  heart  beats  faster  and  works  harder.  It  may  be  that 
it  is  for  both  of  these  reasons  that  the  birds,  which  in  certain  other 
respects  are  more  nearly  related  to  the  reptiles  than  to  the  mammals, 
mount,  as  regards  the  pressure  of  the  blood,  into  the  mammalian  class, 
and  that  a  manometer  in  the  carotid  of  a  goose  will  rise  as  high,  or 
almost  as  high,  as  in  the  carotid  of  a  horse,  a  sheep,  or  a  dog,  while  the 
pressure  in  the  aorta  of  a  tortoise  is  no  higher  than  in  the  aorta  of  a  frog. 
But  we  know  that  the  mere  average  rate  of  the  heart  has  of  itself  com- 
paratively little  influence  on  the  blood-pressure  within  either  group, 
for  the  heart  of  a  rabbit  beats,  on  the  average,  very  much  faster  than 
the  heart  of  a  dog,  and  yet  the  arterial  pressure  in  the  dog  is  certainly 
at  least  as  great  as  in  the  rabbit.  Nor  does  the  size  of  the  body  seem 
to  have  any  definite  relation  to  the  mean  pressure,  even  in  animals 
of  the  same  species ;  and  there  is  no  reason  to  suppose  that  the  pressure 
is  materially  less  in  the  radial  artery  of  a  dwarf  than  in  the  radial  artery 
of  a  giant. 


MECHANICS  OF  THE  CIRCULATION  IN   THE    VESSELS       iij 


Measurement  of  the  Blood-Pressure  in  Man. — In  man  the  blood- 
pressure  has  been  estimated  by  adjusting  over  an  artery  an  instru- 
ment known  as  a  sphygmomanometer  or  sphygmometer,  which,  in 
its  most  modern  form,  consists  essentially  of  a  hollow  rubber  pad  or 
bag  containing  air,  and  connected  with  a  metallic  pressure  gauge  or 
a  mercurial  manometer. 

The  simplest  method  is  that  devised  by  Riva-Rocci  (Fig.  44).  An 
armlet  in  the  form  of  a  broad  rubber  bag,  supported  externally  by 
canvas  or  leather,  is  adjusted  round  the  upper  arm.  The  interior  of  the 
bag  is  connected  with  a  mercury  manometer,  and  also  with  a  strong 
rubber  bulb  provided  with  a  valve.  By  rhythmical  compression  of 
the  bulb  the  pressure  can  be  raised.  Between  the  pressure  bulb  and 
the  rest  of  the  system  is  a  thin  rubber  balloon,  which  by  its  distension 
renders  the  changes  of  pressure  more  gradual.  The  finger  of  the 
observer  is  placed  over  the  radial  artery,  and  the 
pressure  is  raised  until  the  pulse  disappears.  Then 
the  pressure  is  allowed  to  fall  gradually,  and  the 
manometer  reading  at  the  moment  when  the  pulse 
first  reappears  in  the  radial  gives  the  maximum  or 
systolic  pressure  in  the  brachial  artery. 

Instead  of  palpating  the  radial  artery,  a  stetho- 
scope may  be  placed  over  the  brachial  just  below 
the  edge  of  the  armlet,  according  to  the  method  of 
Korotkoff,  by  which,  in  addition  to  the  systolic,  the 
minimum  or  diastolic  pressure  may  be 
determined.  The  pressure  is  raised  some- 
what above  that  necessary  to  obliterate 
the  pulse,  and  then  allowed  to  fall  slowly. 
At  the  moment  when  pulsations  first 
begin  to  break  through  below  the  armlet, 
a  succession  of  sharp  taps,  synchronous 
with  the  pulse,  is  heard.  The  tapping 
sound  grows  rapidly  louder  as  the  artery 
opens  up  more  and  more,  then  abruptly 
diminishes  and  changes  its  character,  and 
gradually  disappears.  Several  phases 
have  been  distinguished  after  the  first 
maximum,  but  their  constancy  and  sig- 
nificance are  still  in  dispute.  Every- 
body agrees  that  the  pressure  shown  by  the  manometer  when  the  sound 
is  first  heard  is  the  systolic  pressure  J'his  corresponds  exactly  with 
the  systolic  pressure  as  determined  by  palpating  the  radial ;  and  it  can  be 
shown  experimentally  that  at  this  point  the  lumen  of  the  brachial  artery 
is  actually  obliterated,  and  not  merely  narrowed  to  such  a  degree  as  to 
prevent  the  passage  of  the  pulse  wave,  while  still  permitting  the  passage 
of  some  blood  (sec  Practical  Exercises,  p.  211). 

The  diastolic  pressure,  according  to  some  observers,  is  the  pressure  at 
which  the  sound  becomes  altogether  inaudible.  Thisscems  to  be  correct, 
but  others  give  it  a  higher  value — namely,  tlie  pressure  at  which  the 
abrupt  change  in  the  sound  occurs.  The  sound  seems  to  be  essentially 
due  to  vibrations  set  up  in  the  walls  of  the  artciy  and  the  structures 
in  contact  with  it  when  it  is  suddenly  opened  by  the  pulse  waves, 
although  these  may  be  intensified  and  otherwise  modified  by  the 
neighbourhood  of  the  inflated  armlet. 

The  sphygmomanometer  of  Erlangcr  (Fig.   15)  is  arranged  to  obtain 

S 


Fig 


44. — Riva-Rocci  Apparatus. 
a,  armlet;  b,  manometer  tube; 
c,  bottle  containing  mercury, 
into\s-hich  b  dips;d,  thin  rubber 
bulb;  e,  thick  rubber  bulb  for 
getting  up  pressure. 


114 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


graphic  records  of  the  pulse,  from  which  both  the  maximum  and  the 
minimum  blood-pressures  may  be  deduced.  The  mean  pressure 
cannot  be  directly  measured,  but  must  lie  much  nearer  to  the  minimum 
than  to  the  maximum,  since  the  line  of  mean  pressure  bisects  the  area 

enclosed  by  the  pulse-curve,   and 
this  area  is  broad  at  the  base  and 
narrow  at  the  apex.     The  rubber 
bag  is  applied  in  the  form  of  a  cuff 
or  armlet  to  the  arm  above  the 
elbow   over   the    brachial    artery. 
It  communicates  with  a  mercury 
manometer,  which  gives  the  pres- 
sure exerted  upon  the  arm.     It  is 
also  connected  with  a  rubber  bulb, 
B,  enclosed  in  a  glass  bulb,  G,  and 
through  a  stopcock  with  a  syringe 
bulb,   V,    provided   with  a  valve. 
The  space  between  B  and  G  com- 
municates (i)  with  the  tambour; 
(2)  with  the  exterior  through  the 
stopcock  by  the  tube  E,  and  also 
through   a   pin-point   opening    in 
the  membrane  of  the 
tambour.     While  the 
armlet   is   being  ad- 
justed the  stopcock  is 
turned    so    that    the 
rubber  bag  is  in  com- 
munication with  the 
external  air  through 
F.     The  same  is  true 
of  the  space  TS  in  the 
glass  bulb.    The  tam- 
bour is  thus  protected 
against  undue  strain 
during      adjustment. 
The  stopcock  is  now 
rotated  so  as  to  cut 
off  the  armlet 
from  the  ex- 
terior and  to 
permit    the 
entrance      of 
air  through  F  from  V, 
which  is  used  as  a  pump 
to  raise  the  pressure,  the 
space  TS  and  the  tam- 
bour being  still  in  com- 
munication    with     the 
exterior.    When  the  de- 
sired pressure  has  been 


\^. 


Fig-  45- — Sphygmomanometer  of  Erlanger. 


reached,  the  stopcock  is  turned  into  an  intermediate  position,  which 
cuts  off  both  the  armlet  and  the  space  TS  from  the  exterior,  and  the 
pulse  IS  then  transmitted  to  the  tambour  and  recorded  on  the  drum. 
By  certam  adjustments  of  the  stopcock  air  can  be  allowed  to  escape 
more  or  less  rapidly  from  the  armlet. 

To   determine    the    maximum   or   systolic   blood-pressure,    the 


air- 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS        115 


pressure  in  the  armlet  is  raised  considerably  (about  50  mm.  Hg)  above 
what  it  is  expected  to  be.  While  the  lever  is  writing  on  the  drum 
the  small  oscillations  due  to  the  impact  on  the  bag  of  the  pulse-waves 
in  the  central  portion  of  the  obliterated  artery,  the  pressure  is  gradually 
diminished  by  allowing  air  to  escape.  At  the  moment  when  the 
pressure  upon  the  arm  falls  below  the  maximum  blood-pressure,  and 
the  pulse-wave  is  first  able  to  break  through  the  brachial  artery,  the 
oscillations  of  the  lever  will  more  or  less  abruptly  increase  in  amplitude. 
The  pressure  shown  by  the  manometer  at  this  point  is  the  systolic 
blood-pressure.  To  obtain  the  minimum  or  diastolic  pressure,  the  air- 
pressure  in  the  armlet  is  raised  somewhat  (10  to  15  mm.  Hg)  above  the 
pressure  expected.  The  pressure  is  diminished  by  5  mm.  Hg  at  a  time, 
records  of  the  oscillations  being  taken  on  the  drum.  The  manometer 
reading  at  the  point  at  which  the  oscillations,  after  reaching  the  maxi- 
mum, begin  abruptly  to  diminish,  corresponds  to  the  minimum  blood- 
pressure. 

In  using  the  sphygmometer  of  Hill  and  Barnard  (Fig.  46),  the  bag 
is  inflated  with  air  till  the  pulsation  indicated  by  the  index  of  the 
pressure  gauge 
reaches  a  maxi- 
mum. The  mean 
pressure  shown 
by  the  gauge  at 
this  point  is 
approximately 
equal  to,  or  some- 
what  greater 
than,  the  mini- 
mum arterial 
pressure.  With 
this  instrument 
it  has  been  found 
that  in  the  bra- 
chial artery  the 
normal  arterial 
pressure  in  most 
healthy  young 
men  is  no  to 
130  mm.  of  mer- 
cury in  the  sitting 

posture.  When  the  person  is  resting  in  the  recumbent  posture,  the 
pressure  may  be  as  low  as  95  mm.  of  mercury.  Hard  work  and  nervous 
strain  may  raise  the  pressure  to  140  or  145  mm.  of  mercury. 

The  effect  of  muscular  exercise  upon  the  pressure  is  influenced  by 
the  nature  of  the  work.  Such  an  effort  as  the  lifting  of  a  heavy  weight 
causes  a  sudden  and  great  increase,  which  is  very  transient.  Thus, 
the  average  arterial  pressure  in  a  number  of  men  was  in  before, 
180  during,  and  no  two  to  three  minutes  after  the  lift  (McCurdy). 
The  rise  of  pressure  in  this  case  is  due  largely  to  the  marked  diminution 
of  the  calibre  of  the  bloodvessels  mechanically  produced  by  the  strong 
and  sustained  contraction  of  the  muscles.  This  increases  the  resistance 
to  the  passage  of  the  blood  along  the  arteries,  while  the  veins  arc  emptied 
by  the  pressure,  and  more  blood  thus  reaches  the  right  side  of  the  heart. 
It  is  obvious  that  the  heart  and  vessels  may  easily  be  exposed  to  an 
injurious  strain  during  such  efforts.  In  such  an  excrci.se  as  running, 
while  the  pressure  mounts  to  some  extent  at  first,  as  already  mentioned, 
the  rise   is  not  maintained,  owing  to  the  dilatation  of  the  cutaneous 


Fig.  46. — Sphygmometer  of  Hill  and  Barnard.  It  consists  of 
a  broad  armlet.  A,  which  is  strapped  round  the  upper  arm. 
On  the  inside  of  the  armlet  is  a  thin  rubber  bag  containing 
air,  and  connected  by  a  T-tube,  B,  with  a  pressure  gauge, 
C,  and  a  small  compressing  air-pump.  D,  fitted  with  a  valve. 


Ii6  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

vessels.  In  the  anterior  tibial  artery  of  a  boy  whose  leg  was  to  be 
amputated,  the  blood-pressure,  measured  by  means  of  a  manometer 
connected  directly  with  the  artery,  was  found  to  vary  from  loo  to 
i6o  mm.,  according  to  the  position  of  the  body  and  other  circum- 
stances. In  a  woman  sixty  years  old,  in  good  health,  the  following 
readings  were  obtained  with  a  sphygmomanometer: 

June  28  .         _         -         -         -  126 — 130  mm.  of  mercury. 

,,     29  -         -         -         -         -  126 — 136 

Aug.     3 132—144 

,.7 134—140 

.,12 136 — 144 

Such  measurements  on  man  show  that  the  mean  blood-pressure 
under  similar  conditions  in  one  and  the  same  artery,  and  in  one  and 
the  same  individual,  may  vary  for  a  considerable  time  only  within 
comparatively  narrow  limits. 

This  relative  constancy  of  the  general  arterial  pressure  is  the 
result  of  a  deUcate  adjustment  between  the  work  of  the  heart,  the 
resistance  of  the  vessels,  and  the  volume  of  the  circulating  liquid. 
The  quantity  of  the  blood  is  tolerably  steady  in  health,  and  con- 
siderable changes  may  be  artificially  produced  in  it  (p.  189)  without 
affecting  the  pressure  in  any  great  degree.  On  the  other  hand,  the 
work  of  the  heart  and  the  peripheral  resistance  are  highly  variable 
and  vastly  influential.  A  narrowing  of  the  arterioles  throughout 
the  body  or  in  some  extensive  vascular  tract  increases  the  peripheral 
resistance ;  and  if  the  heart  continues  to  beat  as  before,  the  pressure 
must  rise.  If  the  arterioles  are  widened,  while  the  heart's  action 
remains  unchanged,  the  pressure  must  fall.  In  like  manner  an 
increase  or  a  decrease  in  the  activity  of  the  heart,  in  the  absence  of  any 
change  in  the  peripheral  resistance,  will  cause  a  rise  or  a  fall  in  the 
blood-pressure.  But  if  a  slowing  of  the  heart  is  accompanied  by  an 
increase  in  the  peripheral  resistance,  or  a  dilatation  of  the  arterioles 
by  an  increase  in  the  activity  of  the  heart,  the  one  change  may  be 
partially  or  completely  balanced  by  the  other,  and  the  pressure  may 
vary  within  narrow  limits  or  not  at  all. 

Not  only  is  the  mean  pressure,  as  measured  in  a  large  artery, 
tolerably  constant,  but  if  recorded  simultaneously  in  two  arteries  at 
different  distances  from  the  heart,  it  is  seen  to  decrease  very  gradu- 
ally so  long  as  the  arteries  remain  large  enough  to  hold  a  cannula. 
It  is  nearly  as  high,  for  instance,  in  the  crural  artery  of  a  dog  as  in 
the  carotid.  It  is  easy  to  see  that  this  must  be  so,  for  the  resistance 
of  the  arteries  between  the  point  where  the  arterioles  are  given  off 
and  the  heart  is  only  a  small  fraction  of  the  total  resistance  of  the 
vascular  path;  and  we  have  said  (p.  84)  that  the  lateral  pressure  at 
any  cross-section  of  a  system  of  tubes  through  which  Hquid  is  flow- 
ing is  proportional  to  the  resistance  still  to  be  overcome.  This  is 
also  the  reason  why  the  pressure  is  always  much  lower  in  the  pul- 
monary artery  and  right  ventricle  than  in  the  aorta  and  left  ventricle 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      117 

(only  one-fifth  to  one-sixth  as  great),  for  the  total  resistance  of  the 
vascular  path  through  the  lungs  is  much  less  than  that  of  the 
systemic  circuit.  In  dogs  with  natural  respiration  the  pressure  in 
the  pulmonary  artery  was  found  to  vary  between  14  and  26  mm.  of 
mercury,  averaging  about  20  mm. 

The  Velocity-Pulse.— We  have  seen  that  the  blood  is  propelled 
through  the  arteries  in  a  series  of  waves  that  travel  from  the  heart 
towards  the  periphery.  The  particles  in  the  front  of  the  pulse-wave 
are  constantly  changing,  but  since  every  section  of  the  arterial  tree 
is  successively  distended,  every  section  contains  more  blood  while 
the  pulse-wave  is  passing  over  it  than  it  contained  immediately 
before.  And  since  there  is  always  a  fairly  free  passage  for  this  blood 
towards  the  periphery,  there  is  a  bodily  transfer  on  the  whole  of  a 
certain  quantity  with  every  wave. 

The  translation  of  the  blood,  instead  of  being  entirely  intermittent, 
as  it  would  be  in  a  rigid  tube  or  in  an  elastic  system  with  a  slow 
action  of  the  central  pump,  is  to  some  extent  constantly  going  on ; 
for  a  portion  of  a  blood-wave  is  always  passing  through  every  section 
of  the  arterial  channel.  Thus,  we  arrive  at  the  same  distinction  as 
to  the  onward  movement  of  the  blood  itself  as  we  previously  reached 
in  regard  to  the  blood-pressure,  the  distinction  between  the  constant 
or  permanent  factor  of  the  velocity  and  the  periodic  factor,  which 
we  may  call  the  velocity-pulse. 

The  Velocity  of  the  Blood. — By  the  velocity  or  rate  of  flow  of  a  river 
we  should  mean,  if  the  flow  were  uniform  throughout  the  whole  cross- 
section,  the  rate  of  movement  of  any  given  portion  or  particle  of  the 
water.  If  we  could  identify  a  portion  of  the  water,  we  could  determine 
the  velocity  by  measuring  the  distance  travelled  over  by  that  portion 
in  a  given  time.  If  the  velocity  was  uniform  over  the  channel,  we  coiild 
predict  the  actual  time  which  would  be  required  to  traverse  any 
fractional  part  of  the  measured  distance.  If,  however,  the  velocity 
of  the  current  changed  from  point  to  point,  then  we  could  only  deduce 
from  our  observation  the  mean  rate  of  the  river  for  the  measured  dis- 
tance. To  determine  the  actual  rate  for  any  given  portion  of  this 
distance  over  which  the  rate  was  uniform,  we  should  have  to  make  a 
separate  observation  for  this  portion  alone. 

But  as  soon  as  we  pass  from  an  ideal  frictionless  river  to  an  actual 
stream,  in  which  the  water  at  the  bottom  and  near  the  banks  flows 
more  slowly  than  that  in  the  middle  and  on  the  surface,  we  are  in  every 
case  restricted  to  the  notion  of  mean  velocity.  We  may  distinguish 
between  the  velocity  of  different  parts  of  the  current,  between  that  of 
the  mid-stream  and  the  side  current,  the  bottom  and  the  surface  layers; 
but  when  we  consider  the  river  as  a  whole,  we  take  cognizance  only 
of  tlic  mean  or  average  velocity.  And  at  any  cross-section  this  may 
be  defined  as  the  volume  of  water  passing  per  hour,  or  whatever  the 
unit  of  time  may  be,  divided  by  the  cross-section  of  the  current.  It  is 
evident  that  this  does  not  enable  us  to  determine  the  actual  velocity 
of  any  given  particle  of  the  water  at  any  given  moment  within  a 
measured  interval ;  nor  docs  it  tell  us  whether  or  not  the  average  velocity 
of  the  current  has  itself  undergone  variations  within  the  period  of 
observation. 


ii8  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

We  have  dwelt  upon  this  point  because  the  measurement  of  the 
velocity  of  the  blood,  to  which  we  must  now  turn,  involves  the  same 
considerations.  Within  the  smaller  arteries,  as  the  microscope 
shows  us,  and  as  we  should  in  any  case  expect  from  what  we  know 
of  fluid  motion,  the  blood-current,  apart  from  the  periodical  varia- 
tions in  its  velocit}^  due  to  the  action  of  the  heart,  varies  in  speed 
from  point  to  point  of  the  same  cross-section.  The  layer  next  the 
periphery  of  the  vessel,  the  so-called  peripheral  plasma-layer  or 
PoiseuiUe's  space,  moves  more  slowly  than  the  central  portion,  the 
axial  stream.  Tn  fact,  we  must  suppose  that  in  the  large  as  well  as 
in  the  small  vessels  the  layer  just  in  contact  with  the  vessel-wall  is 
at  rest,  while  the  stratum  internal  to  this  slides  on  it  and  has  its 
velocity  diminished  by  the  friction.  The  next  layer  again  slides  on 
the  last,  but  since  this  is  already  in  motion,  its  velocity  is  not  so 
much  diminished,  and  so  on.  The  velocity  must  therefore  increase 
as  we  pass  towards  the  axis  of  the  bloodvessel,  and  reach  its  maxi- 
mum there  (p.  191). 

Again,  the  velocity  must  be  altered  wherever  an  alteration  occurs 
in  the  width  of  the  bed,  that  is,  in  the  total  cross-section  of  the 
vascular  system ;  for  since  as  much  blood  comes  back  in  a  given  time 
to  the  right  side  of  the  heart  as  leaves  the  left  side,  the  same  quantity 
must  pass  in  a  given  time  through  every  cross-section  of  the  circula- 
tion. Wherever  the  total  section  of  the  vascular  tree  increases,  the 
blood-current  must  slacken;  wherever  it  diminishes,  the  current 
must  become  more  rapid.  Now,  the  total  section,  increasing  some- 
what as  we  pass  from  the  heart  along  the  branching  arteries,  under- 
goes an  abrupt  augmentation,  and  reaches  its  maximum  in  the 
capillary  region.  It  suddenly  diminishes  again  at  the  venous  end 
of  the  capillary  tract,  and  then  more  gradually  as  we  pass  heart- 
wards  along  the  veins,  but  never  becomes  so  small  as  in  the  arterial 
tract.  We  must,  therefore,  expect  the  mean  velocity  to  be  greatest 
in  the  large  arteries,  less  in  the  veins,  and  least  in  the  arterioles, 
capillaries,  and  venules.  It  must,  of  course,  be  remembered  that  the 
total  section  varies  from  time  to  time  at  any  given  distance  from  the 
heart.  The  capillary  tract  is  especially  variable  in  its  area,  and 
capillaries  full  of  blood  at  one  moment  may  be  collapsed  and  empty 
at  another,  according  to  the  changes  of  calibre  and  pressure  in  the 
arteries  which  feed  and  the  veins  which  drain  them. 

Although  in  strictness  we  are  only  at  present  concerned  with  the 
arteries,  it  will  be  well  to  consider  here  what  a  change  of  velocity  at 
any  part  of  the  vascular  channel  really  implies.  To  say  that  when 
the  channel  widens  the  velocity  diminishes  is  not  to  explain  the 
meaning  of  this  diminution.  A  diminution  of  velocity  implies  a 
diminution  of  kinetic  energy,  and  it  is  necessary  to  know  what  becomes 
of  the  energy  that  disappears.  The  stock  of  energy  imparted  by  the 
contraction  of  the  heart  to  a  given  mass  of  blood  constantly  diminishes 
as  it  passes  round  from  the  aorta  to  the  right  side  of  the  heart,  for 
friction  is  constantly  being  overcome  and  heat  generated.     This  energy, 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS        119 

as  we  have  seen,  exists  in  a  moving  liquid  in  two  forms,  potential  and 
kinetic,  the  former  being  measured  by  the  lateral  pressure,  the  latter 
varying  directly  as  the  square  of  the  velocity.  Whenever  the  velocity, 
and  therefore  the  kinetic  energy,  of  a  given  mass  of  the  blood  is 
diminished  without  a  corresponding  increase  in  the  potential  energy, 
some  of  the  total  stock  of  energy  must  have  been  used  up  to  overcome 
resistance  (p.  84). 

In  a  uniform,  rigid,  horizontal  tube,  as  has  been  already  remarked, 
the  velocity  (and  consequently  the  kinetic  energy)  is  the  same  at 
every  cross-section  of  the  tube,  while  the  potential  energy,  represented 
by  the  lateral  pressure,  diminishes  regularly  along  the  tube.  When 
the  calibre  of  the  tube  varies,  it  is  different.  Suppose,  for  instance, 
that  the  liquid  passes  from  a  narrower  to  a  wider  part,  the  velocity 
must  diminish  in  the  latter.  The  kinetic  energy  of  visible  motion 
which  has  disappeared  must  have  left  something  in  its  room.  Here 
there  are  three  possibilities:  (i)  The  kinetic  energy  that  has  disappeared 
may  be  just  enough  to  overcome  the  extra  friction  in  the  wider  part  of 
the  tube  due  to  eddies  and  consequent  change  of  direction  of  the  lines 
of  flow ;  in  this  case  the  potential  energy  of  a  given  mass  of  the  liquid 
will  be  the  same  at  the  beginning  of  the  wider  part  as  in  the  narrower 
part.  The  lost  kinetic  energy  will  have  been  transformed  into  heat. 
(2)  The  kinetic  energy  which  has  disappeared  may  be  greater  than  is 
enough  to  overcome  the  extra  resistance ;  a  portion  of  it  must,  therefore, 
have  gone  to  increase  the  potential  energy,  and  the  lateral  pressure  will 
be  greater  in  the  wide  than  in  the  narrow  part.  (3)  The  lost  kinetic 
energy  may  be  less  than  enough  to  overcome  the  extra  resistance;  in 
this  case  both  the  lateral  pressure  and  the  velocity  will  be  less  in  the 
wide  than  in  the  narrow  part.  It  has  been  experimentally  shown  that 
when  a  narrow  portion  of  a  tube  is  succeeded  by  a  considerably  wider 
portion,  and  this  again  by  a  narrow  part,  case  (2)  holds;  and  the  liquid 
may,  under  these  conditions,  actually  flow  from  a  place  of  lower  to  a 
place  of  higher  lateral  pressure. 

In  the  vascular  system  the  conditions  are  not  the  same.     The 
widening  of  t Jie  bed  which  takes  place  as  we  proceed  in  the  direction 
of  the  arterial  current  is  not  due  to  the  widening  of  a  single  trunk, 
but  to  the  branching  of  the  channel  into  smaller  and  smaller  tubes. 
In  the  larger  arteries  the  increase  of  resistance  is  so  gradual  that  both 
the  potential  and  the  kinetic  energy  diminish  only  slowly,  and  the 
lateral  pressure  and  velocity  are  not  much  less  in  the  femoral  artery 
than  in  the  aorta  or  carotid.     But  in  the  arterioles  the  friction 
increases  so  greatly  that  although  the  velocity,  and  therefore  the 
kinetic  energy,  in  the  capillary  region  is  much  less  than  in  the 
arteries,  the  amount  of  kinetic  energy  lost  is  not  upon  the  whole 
equivalent  to  the  energy  consumed  in  overcoming  the  extra  resis- 
tance; the  potential  energy  of  the  blood  is  also  drawn  upon,  and  the 
lateral  pressure  falls  sharply  in  the  capillary  region,  as  well  as  the 
velocity.     Where  the  capillaries  open  into  the  veins,  the  lateral  pres- 
sure again  sinks  abruptly,  while  the  velocity  begins  to  increase,  till  in 
the  largest  veins  it  is  probably  about  half  as  great  as  in  the  aorta. 
Where  does  the  extra  kinetic  energy  of  the  blood  in  the  veins  come 
from  ?     To  say  that  the  vascular  chaimel  again  contracts  as  the 
blood  passes  from  the  capillaries  into  the  veins,  and  that,  since  the 


120  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

same  quantity  must  flow  through  every  cross-section  of  the  channeh, 
the  velocity  must  necessarily  be  greater  in  the  narrower  than  in  the 
wider  part,  does  not  answer  the  question.  The  greater  portion  of 
the  kinetic  energy  of  the  arterial  blood  is,  as  we  have  seen,  destroyed, 
or,  rather,  changed  into  an  unavailable  form,  into  heat,  in  the  capil- 
lary region.  The  mean  velocity  of  the  blood  in  the  capillaries  is  not 
more  than  -g^  to  -^rhs  o^  ^^^  velocity  in  the  aorta;  the  kinetic  energy 
of  a  given  mass  of  blood  in  the  capillaries  cannot  therefore  be  more 
than  (ttotj-)^,  or  ^qIqq  of  its  kinetic  energy  in  the  aorta.  In  the  veins, 
taking  the  velocity  at  half  the  arterial  velocity,  the  kinetic  energy 
of  the  mass  would  be  one-fourth  of  that  in  the  aorta,  or  at  least 
10,000  times  as  great  as  in  the  capillary  region.  This  extra  kinetic 
energy  comes  partly  from  the  transformation  of  some  of  the  poten- 
tial energy  of  the  blood.  The  resistance  in  the  veins  is  very  small 
compared  with  that  in  the  capillaries;  less  of  the  potential  energy 
represented  by  the  lateral  pressure  at  the  end  of  the  capillary  tract 
is  required  to  overcome  this  resistance,  and  some  of  it  is  converted 
into  the  kinetic  energy  of  visible  motion,  the  lateral  pressure  at  the 
same  time  falling  somewhat  abruptly.  Contributory  sources  of 
kinetic  energy  in  the  veins  are  the  aspiration  caused  by  the  respira- 
tory movements  and  the  pressure  caused  by  muscular  contraction 
in  general,  which,  thanks  to  the  valves,  always  aids  the  flow  towards 
the  heart.  From  these  two  sources  new  energy  is  supplied,  to  rein- 
force the  remnant  due  to  the  cardiac  systole  (p.  133). 

Measurement  of  the  Velocity  of  the  Blood — i.  Direct  Observation. — 
(fl)  This  method  can  be  applied  to  transparent  parts  by  observing  the 
rate  of  flow  of  the  corpuscles  under  the  microscope.  But  it  is  only 
where  the  blood  moves  slowly,  as  in  the  capillaries,  that  the  method 
is  of  use.  (6)  Part  of  the  path  of  the  blood  through  a  large  vessel  may 
be  artificially  rendered  transparent  by  the  introduction  of  a  glass  tube, 
of  approximately  the  same  bore  as  the  vessel  (Volkmann).  The  tube 
is  filled  with  salt  solution,  and  the  blood  admitted  by  means  of  a  stop- 
cock at  the  moment  of  observation.  The  time  which  the  blood  takes 
to  pass  from  one  end  of  the  tube  to  the  other  is  noted,  and  the  length 
divided  by  the  time  gives  the  velocity  of  the  blood  in  the  tube.  If  the 
calibre  of  the  tube  is  the  same  as  that  of  the  artery,  this  is  also  the 
velocity  in  the  vessel;  but  if  the  calibre  is  different,  a  correction  would 
have  to  be  made.  The  method  is  not  a  good  one,  for  the  reason,  among 
others,  that  the  long  tube  introduces  an  extra  resistance. 

2.  Ludwig's  Stromuhr. — This  instrument  measures  the  quantity  of 
blood  which  passes  in  a  given  time  through  the  vessel  at  the  cross- 
section  where  it  is  inserted.  It  consists  of  a  U-shaped  tube,  with  the 
limbs  widened  into  bulbs,  but  narrow  at  the  free  ends,  which  are  con- 
nected with  a  metal  disc.  By  rotating  the  instrument,  these  ends 
can  be  placed  alternately  in  communication  with  a  cannula  in  the 
central,  and  another  in  the  peripheral,  portion  of  a  divided  artery; 
or  they  can  be  placed  so  that  none  of  the  blood  passes  through  the  bulbs, 
but  all  goes  by  a  short-cut.  One  limb  of  the  instrument  is  filled  with 
oil,  and  the  other  with  defibrinated  blood.  The  limb  containing  the 
oil  is  first  put  into  communication  with  the  central  end,  and  that  con- 
taining the  blood  with  the  peripheral  end,  of  the  artery.     The  blood 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      121 


from  the  artery  rushes  in  and  displaces  the  oil  into  the  other  limb,  the 
dcfibrinated  blood  passing  on  into  the  circulation.  As  soon  as  the  blood 
has  reached  a  certain  height,  indicated  by  a  mark,  the  instrument  is 
reversed  and  the  oil  is  again  displaced  into  the  limb  it  originally 
occupied.     This  process  is  repeated  again  and  again,  the  time  from 

beginning  to  end  of  an  experiment  being 
carefully  noted.  The  number  of  times 
the  blood  has  filled  a  bulb  in  that 
period,  the  capacity  of  the  bulb  and  the 
cross-section  of  the  vessel  being  known, 
all  the  data  required  for  calculating  the 
velocity  of  the  blood  in  the  vessel  have 
been  obtained. 

Suppose,  for  example,  that  the  cap- 
acity of  the  bulb  up  to  the  mark  is  5  c.c, 
and  that  it  is  filled  twelve  times  in  a 
minute,  the  quantity  flowing  through 
the  cross-section  of  the  artery  is  i  c.c, 
or  1,000  cub.  mm.,  per  second.  Let  the 
diameter  of  the  vessel  be  3  mm.,  then  its 

sectional  area  is  tt  x  (  -  )  =^ — ^ — ?=yo6 


..=J^  iU= 


Fig.  47. — Stromuhr  of  Ludwigand 
Dogiel.  A,  B,  glass  bulbs;  a,  a 
metal  disc,  to  which  A  and  G 
are  attached,  and  which  can  be 
rotated  on  the  disc  b;  E,  F,  can- 
nulas attached  to  b,  and  con- 
nected with  the  peripheral  and 
central  ends  of  a  divided  blood- 
vessel. At  the  beginning  of  the 
experiment,  A  and  the  junction 
between  A  and  B  are  filled  with 
oil;  B  is  filled  with  physiological 
salt  solution  or  defibrinated 
blood:  a  being  turned  into  the 
position  shown  in  the  figure,  the 
blood  passes  through  F  and  D 
into  A,  and  the  oil  is  forced  into 
B.  As  soon  as  the  blood  has 
reached  the  mark  w,  the  disc  a, 
with  the  bulbs,  is  rapidly  ro- 
tated, so  that  C  is  now  opposite 
F.  The  blood  now  passes  into 
B,  and  the  oil  is  again  driven 
into  A.  When  the  oil  has 
reached  D,  reversal  is  again 
made,  and  so  on. 


sq.  mm.     The  velocity  is 


7'o6 


•  141  mm 


per  second. 

Various  improvements  in  this  method 
have  been  made,  such  as  a  graphic  regis- 
tration of  the  reversals  of  the  stromuhr. 

3.  A  tube  or  box,  in  which  swings  a 
small  pendulum,  is  inserted  in  the  course 


Fig.  4S.— Pitot's  Tubes. 


of  the  vessel.  The  pendulum  is  deflected 
by  the  blood,  and  the  amount  of  the 
deflection  bears  a  relation  to  the  ve- 
locity of  the  stream  (Vierordt's  h^matachometer  ;  Chauveau  and  Lortet's 
much  more  perfect  dromograph)  (Fig.  41^). 

4.  Pitot's  Tubes. — If  two  vertical  tubes,  a  and  h,  of  the  form  shown  in 
Fig.  48,  be  inserted  into  a  horizontal  tube  in  which  liquid  is  flowing  in 
the  direction  of  the  arrow,  the  level  will  be  higlur  in  a  than  would  hv. 
the  case  in  an  ordinary  side-tube  without  an  elbow;  in  b  it  will  be  lower. 
For  the  moving  liquid  will  exert  a  push  on  the  column  in  a,  and  a  puU 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


on  that  in  b.  The  amount  of  this  push  and  pull  will  vary  with  the 
velocity,  so  that  a  change  in  the  latt.r  will  correspond  to  an  alteration 
in  the  difference  of  level  in  the  two  tubes.  Instruments  on  this  prin- 
ciple have  been  constructed  by  Marey  and  Cybulski,  the  former  regis- 
tering the  movements  of  the  two  columns  of  blood  by  connecting  the 
tubes  to  tambours  provided  with  writing  levers,  the  latter  by  photo- 
graphy (Fig.  50). 

5.  The  electrical  method,  described  on  p.  135, 
for  the  measurement  of  the  circulation  time,  can 
also  be  applied  to  the  estimation  of  the  mean 
velocity  of  the  blood  between  two  cross-sections 
of  the  arterial  path  which  are  separated  by  a 
sufficient  distance.  For  example,  salt  solution 
can  be  injected  into  the  left  ventricle  or  the  be- 
ginning of  the  aorta,  and  the  interval  which  it 
takes  to  reach  a  pair  of  electrodes  in  contact  with, 
say,  the  femoral  artery  determined.  Knowing 
the  distance  between  the  point  of  injection  and 
the  electrodes,  we  can  then  calculate  the  mean 
velocity. 

6.  In  the  calorimetnc  method  of  measuring  the 
quantity  of  blood  which  passes  through  such 
parts  as  the  hands  (or  feet)  in  man,  the  flow  is 
deduced  from  the  quantity  of  heat  given  off  by 
the  part  in  a  given  time,  and  the  difference  be- 
tween the  temperatures  of  the  blood  entering  and 
leaving  the  part.  The  hands  are  immersed  in  a 
large  bath  of  water  (a  few  degrees  below  arterial 
blood  temperature)  for  a  sufficient  time  to  permit 
any  change  of  temperature  of  the  parts  due  to 
the  difference  in  temperature  between  them  and 
the  water  to  be  established.  The  hands  are  then 
rapidly  transferred  to  calorimeters  previously 
filled  with  water  at  the  same  temperature  as  that 
of  the  bath.  All  the  heat  henceforth  given  off 
can  be  assumed  to  be  due  to  the  coohng  of  the 
blood  passing  through  the  hands,  since  the  small 
amount  of  heat  produced  in  the  resting  hands  is 
negligible  for  this  purpose.  The  temperature  of 
the  arterial  blood  at  the  wrist  is  taken  as  0-5°  C. 
below  that  of  the  rectum,  this  being  the  relation 
actually  found  in  a  normal  man.*  The  tempera- 
ture of  the  venous  blood  leaving  the  hand  is  taken 
as  that  of  the  calorimeter,  since  it  has  been  found 
that  blood  withdrawn  from  the  hand  veins  by 
puncture,  and  collected  with  suitable  precautions 
to  prevent  loss  of  heat  as  far  as  possible  and  to 
permit  the  calculation  of  the  unavoidable  loss, 
has    a   temperature    only    a    negligible    fraction 

of   a    degree    above    that    of    the    bath    in    which   the    hand   is   im- 
mersed.    The  flow  in  grammes  per  minute  is  obtained  from  the  formula 

H  I 

Q=      /'r_pfi\-    ~.  where  Q  is  the  quantity  of  blood,  H  the  number 

*  The  temperature  of  the  arterial  blood  at  the  wrist  was  assumed  to  be  the 
calorimeter  temperature  at  which  the  calorimeter  neither  Icses  heat  to  the  hand 
nor  g^ns  heat  from  it.  If  the  heat  production  in  the  resting  hand  is  negligible, 
this  must  correspond  to  the  temperature  of  the  entering  blood. 


Fig.  49.  —  Chauveau's 
Dromograph.  A,  tube 
connected  with  blood- 
vessel; B,  metal  cylin- 
der in  communica- 
tion with  A.  The  upper 
end  of  B  has  a  hole  in 
the  centre,  which  is 
covered  by  a  mem- 
brane, tn,  through 
which  a  lever,  C, 
passes;  C  has  a  small 
disc,  p,  at  its  end, 
which  projects  into  the 
lumen  of  A,  and  is  de- 
flected in  the  direction 
of  the  blood  -  stream 
through  A.  The  de- 
flection is  registered  by 
a  recording  tambour  i  a 
communication  by  the 
tube  E  with  a  tambour 
D,  the  flexible  mem- 
brane of  which  is  con- 
nected with  the  lever 
or  pendulum  C. 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS        123 


of  small  calories  (gramme-calories)  given  off  in  m  minutes,  T  the  tem- 
perature of  the  blood  entering  the  hand,  T'  the  temperature  of  the 
blood  leaving  the  hand,  and  5  the  specific  heat  of  blood  (0-9).  For 
purposes  of  comparison  the  volume  of  the  hands  is  measured,  and  the 
blood-flow  expressed  in  grammes  per  100  c.c.  of  hand  per  minute. 
Further  details  are  given  in  the  Practical  Exercises  (p.  218).  Fig.  51 
shows  one  of  the  calorimeters  on  its  adjustable  stand.  The  collar  of 
thick  felt  which  fits  closely  around  the  wrist,  and  prevents  loss  of  heat 
from  the  orifice  through  which  the  hand  is 
inserted,  is  shown  standing  on  the  top  of 
the  calorimeter,  as  also  the  thermometer 
with  the  small  sliding  lens,  or  '  reader.'  In 
Fig.  108,  p.  219,  the  position  of  the  subject 
with  hands  in  the  calorimeters  is  shown. 


Fig.  50. — Cybulski's  Arrangement  for  recording 
Variations  in  the  Velocity  of  the  Blood.  A,  tube 
connected  with  central,  B  with  peripheral,  end 
of  divided  bloodvessel.  The  blood  stands  higher 
in  the  tube  C  than  in  D.  A  beam  of  light  passing 
through  the  meniscus  in  both  tubes  is  focussed  by 
the  lens  L  on  the  travelling  photographic  plate  E. 
The  velocity  at  any  moment  is  deduced  from  the 
height  of  the  meniscus  in  the  two  tubes  C  and  D. 


Fig.  51. — Calorimeter  with 
stand  for  measuring 
blood-flow  in  hand. 


Of  these  methods,  3  and  4  are  alone  suited  for  the  study  of  the 
velocity-pulse,  that  is,  the  change  of  velocity  occurring  with  every 
beat  of  the  heart.  The  curves  obtanied  by  Chauveau's  dromo- 
graph  show  a  general  agreement  with  blood-pressure  tracings  taken 
by  a  spring  manometer,  and  with  records  of  the  external  pulse 
obtained  by  a  sphygmograph.  There  is  a  primary  increase  of 
velocity  corresponding  with  the  ventricular  systole,  and  a  secondary 
increase  corresponding  with  the  dicrotic  wave  (Fig.  54).  Like  all 
the  other  pulsatory  phenomena,  the  velocity-pulse  disappears  in  the 
capillaries,  and  is  only  present  under  exceptional  circumstances  in 
the  veins. 


124  THE  CIRCULATION  OF  THE  BLOOD  ANL>  LYMPH 

Fick,  from  a  comparison  of  sphygmographic  and  plethysmographic 
tracings  (p.  128),  taken  simultaneously  from  the  radial  artery  and 
the  hand,  has  demonstrated  that  in  man  the  velocity-pulse  exhibits 


Fig.  52.  Fig.  53. 

Fig.  52. — The  highest  of  the  three  curves  is  a  plethysmographic  record  taken  from 
the  hand;  the  second  curve  is  a  sphygmogram  taken  simultaneously  from  the 
corresponding  radial  artery;  the  lowest  (interrupted)  curve  is  the  curve  of  velocity 
deduced  from  a  comparison  of  the  first  two  (Fick). 

Fig.  53. — Simultaneous  plethysmographic  and  sphygmographic  tracings. 

the  same  general  characters  as  in  animals  (Figs.  52  and  53).  And 
V.  Kries  has  confirmed  Fick's  conclusions  by  actual  records  of  the 
velocity-pulse  obtained  by  means  of  an  arrangement  called  a  gas 
tachograph  (Fig.  55). 


Fig  54- — Simultaneous  Tracings  of  the  Velocity  (Upper  Curve)  and  Pressure  (Lower 
Curve)  (Lortet).  The  tracings  were  taken  from  the  carotid  artery  of  a  horse. 
The  curve  of  velocity  was  obtained  by  the  dromograph.  The  dicrotic  wave  is 
marked  on  it.  The  slightly  curved  ordinates  drawn  through  the  curves  indicate 
corresponding  points. 


This  consists  of  a  plethysmograph  connected  with  the  tube  of  a  gas- 
burner.  When  the  part  enclosed  in  the  plethysmograph  expands,  air 
issues  from  the  connecting  tube,  and  causes  an  increase  in  the  height  of 
the  flame.  When  the  part  shrinks,  air  is  drawn  in  from  the  flame, 
which  is  depressed.  Since  tlie  speed  of  tlic  blood  in  the  veins  may  be 
considered  constant  during  the  time  of  an  experiment,  the  rate  at  which 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS        125 

the  volume  of  the  part  alters  at  any  moment  is  a  measure  of  the  pulsa- 
tory change  of  velocity  in  tlie  arteries  of  the  part.  And  by  photo- 
graphing the  movements  of  the  flame  on  a  travelling  sensitive  surface, 
the  velocity-pulse  is  directly  recorded. 

The  mean  velocity,  like  the  mean  blood-pressure,  is  more  variable 
in  the  large  arteries  near  the  heart  than  in  the  smaller  and  more 
di  stant  arteries. 
Dogiel  found  in 
measurements 
taken  with  the 
stromuhr  (a  good 
instrument  for  tlic 
estimation  of  mean 
speed),  within  a 
period  of  t\\'o 
minutes,  velocities 
ranging  from  over 
200  mm.  to  under 
100  mm.  per  second 
in  the  carotid  of  the 
rabbit,  and  from  over  500  mm.  to  less  than  250  mm.  in  the  carotid  of 
the  dog.  Chauveau,  with  the  dromograph,  found  the  velocity  in  the 
carotid  of  a  horse  to  be  520  mm.  per  second  during  systole,  150  mm 
during  the  pause,  220  mm.  during  the  period  of  the  dicrotic  wave. 

It  is  probable,  however,  that,  if  these  numbers  are  at  all  accurate 
for  bloodvessels  in  the  immediate  neighbourhood  of  the  heart,  there 
must  be  a  rapid  diminution  in  the  velocity  even  while  the  arteries 
are  still  of  considerable  calibre.  For  it  has  been  found  by  the 
electrical  method  that,  in  ansesthetized  dogs  at  any  rate,  as  is  shown 
in  the  following  table,  the  mean  velocity  between  the  origin  of  the 
aorta  and  the  crural  artery  in  the  middle  of  the  thigh  is  usually  less 
than  100  mm.  per  second. 


Fig-  55- — Photographic  Record  of  the  Velocity-Pulse  ob- 
tained by  the  Gas  Tachograph  (v.  Kries).  The  upper 
curve  is  the  photographic  representation  of  the  move- 
ments of  the  flame,  and  corresponds  to  the  curve  of 
velocity. 


Distance 

Average  Time  be- 

Average 
Velocity 

Average 

Distance 

traversed  per 

No.  of 

Body- 

between  Point 

tween  Injection 

Average 

Experi- 

weight 

of  Injection  and 

and  Arrival  of  the 

Pulse-rate 

ment. 

in  Kilos. 

Electrodes, 
in  Millimetres. 

Salt  Solution,  in 
Seconds. 

per  Minute. 

in  Milli- 
metres. 

in  Milli- 
metres. 

I. 

34-55 

420 

4*62 

105 

90 -9 

51-9 

II. 

17-5 

495 

57 

69 

86-8 

75-4 

III. 

14-99 

400 

5-0 

102 

8o-o 

47-0 

IV. 

10-32 

470 

7-12 

74-5 

72-9 

58-7 

V. 

7-165 

330 

7-83 

46-3 
(weak  beat) 

42-1 

54-5 

1 

In  I.  the  injecting  cannula  was  in  the  descending  part  of  the  thoracic 
aorta,  in  V.  at  the  very  origin  of  the  aorta,  and  in  II.,  III.,  and  IV. 
in  the  left  ventricle. 


126 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


As  to  the  speed  of  the  blood  in  the  arteries  of  man,  our  data  are 
insufficient  for  more  than  a  loose  estimate.  But  it  does  not  seem 
likely  that  the  mean  velocity  of  a  particle  of  blood  in  moving  from 
the  heart  to  the  femoral  artery  can  exceed  150  mm.  per  second  for 
the  whole  of  its  path.  This  would  correspond  to  rather  more  than 
a  third  of  a  mile  per  hour.  In  the  arch  of  the  aorta  the  average 
speed  may  be  twice  as  great.  '  The  rivers  of  the  blood  '  are,  even 
at  their  fastest,  no  more  rapid  than  a  sluggish  stream.  A  red  cor- 
puscle, even  if  it  continued  to  move  with  the  velocity  with  which  it 
set  out  through  the  aorta,  would  only  cover  about  15  miles  in  twenty- 
four  hours,  and  would  require  five  years  to  go  round  the  world. 

The  average  flow  through  the  hands  of  a  healthy  young  man,  as 
determined  in  eighteen  experiments  on  different  dates  ranging  over 
two  years,  at  room  temperatures  varying  from  19°  to  27°  C,  was 
I2'8  grammes  per  100  c.c.  of  hand  per  minute  for  the  right  hand,  and 
12*3  grammes  for  the  left.  Ten  of  the  observations  on  this  man  are  con- 
densed in  the  table. 


Date. 

Temperature  of— 

Blood-flow  in  Grammes 

per  100  c.c.  of  Hand 

per  Minute. 

Room. 

Arterial 
Blood. 

Calorim, 

Right. 

Left. 

November  30,  1910  - 
December  22,  1910  - 
February  i,  191 1       - 
March  17,  191 1 
May  24,  1911    - 
Novembers,  191 1     - 
November  9,  1911     - 
November  15,  191 1  - 
December  11,  1911   - 
March  26,  1913 

20'2 
2I*I 

22-8 
2I'I 
27*0 
25-1 
24.1 
25-2 
24-5 
24-5 

36-6 
36-8 

36-9 
36-6 
36-8 
367 
367 
36-8 
36-6 
36-6 

28'0 
29.7 

30-3 
29.9 

30-9 
30-0 

30-8 
30-8 
3I-I 

31-5 

10*1 

137 
12-6 

II-8 
i8-5 

I2T 
137 

I4'0 

12-4 

147 

9-4 

12-5 
127 

II-3 

17-5 
117 

12-5 

13-8 

I2'0 

I5-I 

Since  the  great  function  of  the  circulation  in  the  skin  is  the  regulation 
of  the  temperature  of  the  body  (see  Chapter  XII.),  the  blood-flow  in 
the  hands  is,  of  course,  much  influenced  by  the  external  temperature. 
Thus,  by  far  the  greatest  flow  in  the  above  table  corresponds  to  the 
high  room  temperature  of  27°  C.  With  a  given  external  temperature, 
the  degree  of  humidity  of  the  air  also  affects  the  flow.  Under  similar 
conditions  of  external  temperature  and  daily  routine,  including  diet, 
the  hand  flow  in  one  and  the  same  individual  does  not  vary  greatly 
when  measured  at  about  the  same  hour  on  different  days.  Different 
individuals,  when  tested  under  apparently  similar  conditions,  show  a 
greater  range  in  the  blood-flow.  Some  normal  persons  know  and  say 
that  their  hands  are  habitually  cool  or  cold;  others,  like  the  man  on 
whom  the  above  results  were  obtained,  that  their  hands  are  habitually 
warm.  The  former  may  be  expected  to  show  a  relatively  small,  and 
the  latter  a  relatively  large,  flow  of  blood  through  the  hands.     It  is 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS 


127 


possible  that  such  habitual  differences  are  associated  with  differences 
in  the  total  heat  value  of  the  food  consumed  or  in  the  proportions  of 
the  various  food  substances,  especially  of  proteins  (see  p.  596), 
for  it  is  well  known  that  even  persons  engaged  in  the  same  work,  and 
living  under  similar  external  conditions,  may  differ  greatly  in  their 
dietetic  habits,  both  as  to  quantity  and  quality  of  the  food.  And  since 
the  cutaneous  circulation  is  by  far  the  most  important  factor  in  tlie 
loss  of  heat  from  the  body,  the  hearty  eaters,  other  things  being  equal, 
may  be  expected  to  have  the  largest  blood-flow  through  parts  like  the 
hands.  The  importance  of  the  flow  through  the  skin  in  the  total  hand 
flow  is  illustrated  by  the  fact  that  the  flow  per  unit  of  volume  through 
the  distal  half  of  the  hand,  which,  of  course,  has  a  large  surface  in 
proportion  to  its  volume,  is  considerably  greater  than  through  the  hand 
as  a  whole.  For  the  forearm  the  flow  per  100  c.c.  is,  in  its  turn,  much 
less  than  in  the  hand  (Hewlett) .  In  the  foot  the  blood-flow,  as  estimated 
by  the  calorimetric  method,  is  smaller  per  unit  of  volume  of  the  part 
than  in  the  hand,  the  ratio  of  foot  flow  to  hand  flow  per  100  c.c.  of  the 
part  usually  lying  in  normal  persons  between  i  to  3  and  i  to  2.  This 
is  largely  due  to  the  proportionally  greater  proportion  of  skin  in  the 
hand,  as  well  as  to  the  smaller  proportion  of  bone,  which  has  not  an 
active  circulation.  In  the  sitting  position  the  following  results  were 
obtained  for  the  flow  in  the  feet  on  the  person  whose  hand  flows  have 
been  given  above : 


Date. 

Blood-flow  in  Grammes 
Temperature  of—                    per  loo  c.c.  of  Foot 
per  Minute. 

Room. 

Arterial 
Blood. 

Calorim.l        Right. 

LefL 

May  2,  191 1     -         •         - 
May  18,  191 1  -         -         - 
June  17,1911   -         -         - 
March  26,  1913 

25-2 
26-4 
21-8 

24-5 

36-8 
36-9 

37-0 
36-5 

30-4          3-5 
31-4          3-5 
30-6          4-9 

31-4          3-9 

4-2 

4-1 

The  great  variations  in  the  vascularity  of  different  organs  and  parts, 
as  revealed  by  the  examination  of  injected  specimens  or  by  inspection 
of  the  organs  during  life,  indicate  that  there  must  be  great  differences 
in  the  blood-flow.  Observations  with  the  stromuhr  in  animals  have 
shown  that  this  is  the  case.  The  following  list  gives  the  number  of 
c.c.  of  blood  passing  per  minute  through  100  grammes  of  organ,  according 
to  the  results  of  Burton-Opitz,  Tigerstedt,  and  other  observers : 

Posterior  extremity. .  ..  5 

Skeletal  muscle  . .  . .  12 

Head  , .          . .  . .  . .  20 

Stomach         . .  . .  . .  21 

Liver  (arterial)  . .  . .  25 

Intestines      . .  . .  . .  31 

Spleen            . .  . .  • .  58 

The  Volume-Pulse. — When  the  pulse-wave  reaches  a  part  it  dis- 
tends its  arteries,  increases  its  volume,  and  gives  rise  to  what  may 
be  called  the  volume-pulse. 


Liver  (venous) 

59 

Liver  (total)    . . 

..       84 

Brain    . . 

..      136 

Kidney 

..      150 

Adrenal 

200-300 

Thyroid  gland 

560 

128 


THE  CIRCULATION  OF  THE   BLOOD  AND  LYMPH 


This  may  be  readily  recorded  by  means  of  a  plethysmograph,  an 
instrument  consisting  essentially  of  a  chamber  with  rigid  walls  which 
enclose  the  organ,  the  intervening  space  being  filled  up  with  liquid 
(Fig.  56).  The  movements  of  the  liquid  are  transmitted  either  through 
a  tube  filled  with  air  to  a  recording  tambour,  or  directly  to  a  piston  or 
float  acting  upon  a  writing  lever.  Special  names  have  been  given  to 
plethysmographs  adapted  to  particular  organs;  for  example,  Roy's 
oncometer  for  the  kidney.  The  method  has  been  successfully  applied 
to  the  investigation  of  circulatory  changes  in  man,  a  finger,  a  hand  or 
an  entire  limb  being  enclosed  in  the  plethysmograph.  With  a  fairly 
sensitive  arrangement,  every  beat  of  the  heart  is  represented  on  the 
tracing  by  a  primary  elevation  and  a  dicrotic  wave  (Fig.  57). 

The  general  appearance  of  the 
curve  is  very  similar  to  that  of  an 
ordinary  pulse-tracing,  though 
there  are  some  differences  of  detail, 
especially  in  the  time  relations.  A 
volume-pulse  has  been  actually  ob- 
served not  only  in  limbs  and  por- 
tions of  Hmbs,  but  also  (in  animals) 
in  the  spleen,  kidney  and  brain 
and  other  organs,  and  in  the  orbit. 


Fig.  56. — -Plethysmograpli  (MosST*).  M,  balanced  test-tube,  in  communication  with 
the  glass  vessel,  D,  which  contains  the  arm,  escape  of  water  being  prevented  by 
the  rubber  cuff,  A.  When  water  passes  from  vessel  D  to  M,  or  from  M  to  D, 
M  moves  down  or  up,  and  its  movements  are  recorded  by  the  writing-point  N. 
M  is  steadied  by  the  liquid  in  P,  into  which  it  dips. 

The  so-called  cardio-pneumatic  movements  also  constitute  a 
volume-pulse,  although  of  complex  origin.  This  name  is  given  to 
the  rhythmical  changes  of  pressure  accompanying  the  beat  of  the 
heart,  which  can  be  detected  in  the  air  of  the  respiratory  passages 
when  one  nostril  is  connected  with  a  recording  tambour,  or  water 
manometer,  the  other  nostril  and  the  mouth  being  closed,  and  the 
respiration  suspended  in  inspiration,  with  the  glottis  open.      Or  the 


MECHANICS  OF  THE  CIRCULATION  IN  THE  VESSELS      129 

mouth  may  be  connected  with  the  recording  apparatus,  the  nostrils 
being  closed.  One  factor  in  the  production  of  these  movements  may- 
be the  change  of  blood-volume  in  the  soft  tissues  of  the  mouth,  naso- 
pharynx, and  perhaps  also  in  the  lower  respiratory  passages  accom- 
panying the  heart-beat.  Another  factor,  and  a  more  influential  one, 
is  the  rhythmical  alteration  of  pressure  caused  directly  by  the  alter- 
nate systole  and  diastole  of  the  heart  in  the  air  contained  in  the 
lung-tissue  surrounding  it,  which  acts  as  a  kind  of  air  plethysmo- 
graph.  One  interesting  way  in  which  the  cardio-pneumatic  move- 
ments may  reveal  themselves  is  by  a  variation  with  each  beat  of  the 
heart  in  the  intensity  of  a  note  prolonged  in  singing,  especially  after 
fatigue  has  set  in.  Upon  the  whole,  the  air-pressure  falls  during 
systole,  owing  to  the  expulsion  of  blood  from  the  chest,  and  rises 
during  diastole.  The  main  cardio-pneumatic  movement  is,  there- 
fore, a  systolic  inspiration  and  a  diastolic  expiration  (Practical 
Exercises,  p.  297). 

Doubtless  the  weight  of  an  organ  would  also  show  a  pulse  correspond- 
ing to  the  beat  of  the  heart,  and  so  would  the  temperature — at  least, 
of  the  superficial  parts.     For  the  amount  of  heat  given  off  by  the  blood 


lig.  57. — Plethysmograpli  Tracing  from  Ann.  The  tracing  was  taken  by  means  of 
a  tambour  connected  with  the  plethysmograph.  The  dicrotic  wave  is  distinctly 
marked. 

to  the  skin  increases  with  its  mean  velocity,  and,  therefore,  although 
the  difference  may  not  in  general  be  measurable,  more  heat  is  pre- 
sumably given  oft  during  the  systolic  increase  of  velocity  than  during 
the  diastolic  slackening.  And  this,  along  with  other  considerations, 
suggests  that,  at  any  rate  in  certain  situations  and  under  certain  con- 
ditions, there  may  even  be  a  pulse  of  chemical  change ;  that  is,  a  slight 
and  as  yet  doubtless  inappreciable  ebb  and  flow  of  metabolism  corre- 
sponding to  the  rhythm  of  the  heart. 

The  Circulation  in  the  Capillaries. — From  the  arteries  the  blood 
passes  into  a  network  of  narrow  and  thin-walled  vessels,  the  capil- 
laries, which  in  their  turn  are  connected  with  the  finest  rootlets  of 
the  veins.  Physiologically,  the  arterioles  and  venules  must  for 
many  purposes  be  included  in  the  capillary  tract,  but  the  great 
anatomical  difference — the  presence  of  circularly-arranged  muscular 
fibres  in  the  arterioles,  their  absence  in  the  capillaries — has  its 

9 


I30  THE  CIRCULATION^  OF  THE  BLOOD  AND  LYMPH 

physiological  correlative.  The  calibre  of  the  arterioles  can  be 
altered  by  contraction  of  these  fibres  under  nervous  influences ;  the 
cahbre  of  the  capillaries,  although  it  varies  passively  with  the  blood- 
pressure,  and  is  possibly  to  some  extent  affected  by  active  con- 
traction of  the  endothelial  cells,  cannot  be  under  the  control  of  vaso- 
motor nerves  acting  on  muscular  fibres  (but  see  p.  171). 

Harvey  had  deduced  from  his  observations  the  existence  of 
channels  between  the  arteries  and  the  veins.  Malpighi  was  the  first 
to  observe  the  capillary  blood-stream  with  the  microscope,  and  thus 
to  give  ocular  demonstration  of  the  truth  of  Harvey's  brilUant 
reasoning.  He  used  the  lungs,  mesentery  and  bladder  of  the  frog. 
The  web  of  the  frog,  the  tail  of  the  tadpole,  the  wing  of  the  bat,  the 
mesentery  of  the  rabbit  and  rat,  and  other  transparent  parts,  have 
also  been  frequently  employed  for  such  investigations.  From  the 
apparent  velocity  of  the  corpuscles  and  the  degree  of  magnification, 


Fjg  58. — Diagram  to  Illustrate  the  Slope  of  Pressure  along  the  Vascular  System. 
A,  arterial;  C,  capillary;  V,  venous  tract.  The  interrupted  line  represents  the 
line  of  mean  pressure  in  the  arteries,  the  wavy  line  indicating  that  the  pressure 
varies  with  each  heart -beat.  The  line  passes  below  the  abscissa  axis  (line  of 
zero  or  atmospheric  pressure)  in  the  veins,  indicating  that  at  the  end  of  the  venous 
system  the  pressure  becomes  negative. 

it  is  easy  to  calculate  the  velocity  of  the  capillary  blood-stream. 
It  has  been  estimated  at  from  02  to  08  mm.  per  second  in  different 
parts  and  different  animals. 

The  comparative  slowness  of  the  current  and  the  disappearance 
of  the  pulse  are  the  chief  characteristics  of  the  capillary  circulation. 
The  explanation  we  have  already  found  in  the  great  resistance  of 
the  narrow  arterioles  and  the  much-branched  capillary  vessels. 
Although  the  average  diameter  of  a  capillary  is  only  about  10  ^ 
(5  to  20  fj,  in  different  parts  of  the  body),  the  number  of  branches 
is  so  prodigious  that  the  total  cross-section  of  the  systemic  capillary 
tract  has  been  estimated  at  500  to  700  times  that  of  the  aorta. 
Such  estimates  are,  of  course,  by  no  means  exact. 

The  total  cross-section  of  the  vascular  channel  gradually  widens 
as  it  passes  away  from  the  left  ventricle.     In  the  capillary  region 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      131 


it  undergoes  a  great  and  sudden  increase.  A  part  of  this  increase 
is  to  be  attributed  to  the  arterioles,  which,  although  individually 
very  narrow,  have  a  total  bed  considerably  greater  than  that  of  the 
arteries  from  which  they  spring.  Where  the  arterioles  pass  into 
the  capillaries  proper,  a  further  and  a  still  greater  and  more  abrupt 
increase  in  the  bed  occurs.  At  the  venous  end  of  this  region  the 
cross-section  is  again  somewhat  abruptly  contracted,  and  then 
gradually  lessens  as  the  right  side  of  the  heart  is  approached ;  but 
the  united  sectional  area  of  the  large  thoracic  veins  is  greater  than 
that  of  the  aorta. 

Attempts  have  been  made  to  measure  the  blood-pressure  in  the 
capillaries  by  weighting  a  small  plate  of  glass  laid  on  the  back  of  one  of 
the  fingers  behind  the  nail,  until  the  capillaries  are  just  emptied,  as 
shown  by  the  paling  of  the  skin  (v.  Kries),  or  by  observing  the  height  of 
a  column  of  liquid  that 
just  stops  the  circula- 
tion in  a  transparent 
part  (Roy  and  Graham 
Brown).  The  last- 
named  observers  found 
that  a  pressure  of  100 
to  150  mm.  of  water 
(about  7  to  II  mm. 
of  Hg)  was  needed  to 
bring  the  blood  to  a 
standstill  in  the  capil- 
laries and  veins  of  the 
frog's  web;  that  is, 
about  a  third  of  the 
blood-pressure  in  the 
frog's  aorta.  The  pres- 
sure in  the  capUlaries 
at  the  root  of  the  nail 
in    man     varies    from 

30  to  50  mm.  of  mercury,  as  estimated  by  the  method  of  v.  Kries.  But 
the  method  is  exposed  to  serious  errors.  The  method  of  measuring  the 
venous  pressure  described  on  p.  132  can  also  be  applied  to  the  capillaries, 
and  is  somewhat  more  satisfactory. 

Under  certain  conditions  the  pulse-wave  may  pass  into  the 
capillaries  and  appear  beyond  them  as  a  venous  pulse.  Thus,  we 
shall  see  that  when  the  small  arteries  of  the  submaxillary  gland  are 
widened,  and  the  vascular  resistance  lessened,  by  the  stimulation  of 
the  chorda  tympani  nerve,  the  pulse  passes  through  to  the  veins. 
And,  normally,  a  pulse  may  be  seen  in  the  wide  capillaries  of  the 
nail-bed — especially  when  they  are  partially  emptied  by  pressure — 
as  a  flicker  of  pink  that  comes  and  goes  with  every  beat  of  the  heart. 

We  have  seen  that  the  lateral  pressure  at  any  point  of  a  uniform 
rigid  tube  through  which  water  is  flowing  is  proportional  to  the  amount 
of  resistance  in  the  portion  of  the  tube  between  this  point  and  the  outlet. 
In  any  system  of  tubes  the  sum  of  the  potential  and  kinetic  energy 
must  diminish  in  the  direction  of  the  flow;  and  although  the  problem 


Fig-  59. — Relation  of  Blocd- Pressure,  Velccity,  and 
Cross-Section.  The  curv^es  P.  V,  and  S  represent  the 
blood-pressure,  velocity  of  the  blood,  and  total  cross- 
section  respectively  in  the  arteries  A,  capillaries  C. 
and  veins  V. 


132         THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

is  complicated  in  the  vascular  system  by  the  branching  of  the  channel 
and  the  variation  in  the  total  cross-section,  yet  theory  and  experiment 
agree  that  in  the  larger  arteries  the  lateral  pressure  diminishes  but 
slowly  from  the  heart  to  the  periphery,  the  resistance  being  small  com- 
pared with  the  resistance  of  the  whole  circuit.  In  the  capillary  region 
the  vascular  resistance  abruptly  increases ;  the  velocity  (and  therefore 
the  kinetic  energy)  abruptly  diminishes,  and  the  lateral  pressure  falls 
much  more  steeply  between  the  beginning  and  the  end  of  this  region 
than  between  the  heart  and  its  commencement.  In  the  veins  only  a 
small  remnant  of  resistance  remains  to  be  overcome,  and  the  lateral 
pressure  must  sink  again  rather  suddenly  about  the  end  of  the  capillary 
tract.  Fig.  59  shows  by  a  rough  diagram  the  manner  in  which  the 
pressure,  velocity  and  cross-section  probably  change  from  part  to  part 
of  the  vascular  system. 

The  Circulation  in  the  Veins. — The  slope  of  pressure,  as  we  have 
just  explained,  must  fall  rather  suddenly  near  the  beginning  and 
near  the  end  of  the  capillary  tract.  It  continues  falling  as  we  pass 
along  the  veins,  till  the  heart  is  again  reached.  In  the  right  heart, 
and  in  the  thoracic  portions  of  the  great  veins  which  enter  it,  the 
pressure  may  be  negative — that  is,  less  than  the  atmospheric 
pressure.  And  since  nowhere  in  the  venous  system  is  the  pressure 
more  than  a  small  fraction  of  that  in  the  arteries,  its  measurement 
in  the  veins  is  correspondingly  difficult,  because  any  obstruction 
to  the  normal  flow  is  apt  to  artificially  raise  the  pressure.  A  man- 
ometer containing  some  lighter  liquid  than  mercury,  such  as  water 
or  a  solution  of  sodium  citrate  or  magnesium  sulphate,  is  usually 
employed,  so  that  the  difference  of  level  may  be  as  great  as  possible. 
In  the  sheep  the  pressure  was  found  to  be  3  mm.  of  mercury  in  the 
brachial,  and  about  11  mm.  in  the  crural  vein.  Burton-Opitz 
obtained  the  following  pressures  in  dogs  (of  about  15  kilos) :  left 
facial  vein,  5-1 ;  right  external  jugular,  -  o-ii ;  central  end  of  superior 
vena  cava,  —  2*8 ;  femoral  vein,  5-4;  renal  vein,  lo-g;  portal  vein, 
8*9  mm.  of  mercury. 

Estimation  of  Venous  Pressure  in  Man. — The  venous  pressure  in  man 
has  been  estimated  by  several  observers  with  more  or  less  satisfactory 
results.  The  best-known  method  is  that  of  v.  Recklinghausen.  A 
circular  rubber  bag,  with  a  central  opening,  is  laid  over  tlie  course  of 
a  vein,  so  that  the  vein  can  be  observed  through  the  opening,  as  in 
Fig.  60.  The  bag  is  smeared  with  glycerin.  A  glass  plate  is  laid  over 
the  opening  and  held  firmly,  so  that  the  vein  and  the  surrounding  skin 
are  in  a  closed  chamber.  The  bag  is  provided  with  a  side-tube,  which 
connects  it  with  a  pump  and  a  water  manometer.  By  means  of  the 
pump  air  is  forced  into  the  bag  till  the  vein  is  just  seen  to  collapse. 
The  pressure  indicated  on  the  manometer  at  this  moment  is  taken  as 
the  pressure  in  the  vein. 

By  means  of  a  modification  in  this  method,  Eyster  and  Hooker  have 
found  that  the  pressure  in  the  small  veins  of  the  arm  or  hand  generally 
varies  between  3  and  10  cm.  of  water.  In  conditions  of  congestion  of 
the  venous  system  the  pressure  may  rise  to  20  cm.  of  water  (saj'^  15  mm. 
of  mercury)  or  more. 

In  making  this  measurement  it  is  necessary  to  take  account  of  the 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      133 


position  of  the  vein,  since  the  hydrostatic  factor  (p.  188)  in  the  venous 
pressure  is  so  important.  Thus  it  is  obvious  that  the  pressure  in  the 
veins  of  the  hand  will  be  greater  when  it  is  hanging  down  than  when 
it  is  raised  to  level  of  the  heart  or  above  it.  Accordingly,  the  actual 
readings  of  the  manometer  must  always  be  corrected  for  the  vertical 
distance  between  the  vein  and  the  heart,  the  height  of  a  column  of 
blood  equal  to  this  distance  being  deducted  from  or  added  to  the 
manometer  reading,  according  to  whether  the  vein  is  below  or  above 
the  heart  level.  F"or  practical  purposes  the  heart  level  is  supposed  to 
correspond  to  the  lower  end  of  the  sternum  (costal  angle). 

For  the  measurement  of  the  pressure  in  the  right  auricle,  the  follow- 
ing simple  and  elegant  method  has  been  given  by  Gaertner,  following 
a  suggestion  of  Frey:  He  raises  the  arm  of  the  sitting  patient,  and 
observes  a  small  vein  on  the  back  of  the  hand.  At  the  moment  when  the 
vein  collapses  the  elevation  of  the  arm  is  stopped,  and  the  vertical 
distance  between  the  vein  and  the  heart  measured.  This  expressed  in 
millimetres  of  blood  {i.e.,  approximately  of  water)  is  the  pressure  in 
the  auricle,  since  the  veins  of  the  arm  constitute  manometer  tubes 
connected  with  the  auricle. 

The  venous  pressure  being  so  low,  or,  in  other  words,  the  potential 
energy  which  the  systole  of  the  heart  imparts  to  the  blood  being  so 
greatly  exhausted 
before  it  reaches 
the  veins,  other  in- 
fluences begin  here 
appreciably  to 
affect  the  blood- 
stream : 

I.  Contraction  of 
the  Muscles.  — This 
compresess  the 
neighbouring  veins, 


Fig 

(V 


60. — Diagram  of  Measurement  of  Venous  Pressure 
Recklinghausen).     H,  back  of  hand,  with  V.  a  vein; 
B,  the  rubber  bag  with  central  opening;  T,  tube  leading 
from  bag  to  manometer  and  pump ;  G,  glass  plate. 


and  since  the  blood  is  compelled  by  the  valves,  if  it  moves  at 
all,  to  move  towards  the  heart,  the  venous  circulation  is  in  this 
way  helped. 

2.  Aspiration  of  the  Thorax.— In  inspiration  the  intrathoracic 
pressure,  and  therefore  the  pressure  in  the  great  thoracic  veins,  is 
diminished,  and  blood  is  drawn  from  the  more  peripheral  parts  of 
the  venous  system  into  the  right  heart  (p.  225). 

3.  Aspiration  of  the  Heart.— When  the  heart  after  its  contraction 
suddenly  relaxes,  the  endocardiac  pressure  becomes  negative,  and 
blood  is  sucked  into  it,  just  as  when  the  indiarubber  ball  of  a  syringe 
is  compressed  and  then  allowed  to  expand.  But  we  cannot  attribute 
any  great  importance  to  this;  and,  of  course,  it  is  only  the  relaxa- 
tion of  the  right  ventricle  which  could  directly  affect  the  venous 
circulation. 

4.  Every  change  of  position  of  the  limbs,  as  in  walking,  aids  the 
venous  circulation  (Braune),  and  this  independently  of  the  muscular 
contraction.   When  the  thigh  of  a  dead  body  is  rotated  outwards,  and 


134  2'^^'  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

at  the  same  time  extended,  a  manometer  connected  with  the  femoral 
vein  shows  a  negative  pressure  of  5  to  10  mm.  of  water.  When  the 
opposite  movements  are  made,  the  pressure  becomes  positive. 

It  follows  from  the  number  of  casually-acting  influences  which 
affect  the  blood-flow  in  the  veins  that  it  cannot  be  very  regular  or 
constant.  We  have  seen  that  in  the  great  arteries  there  is  a  con- 
siderable variation  of  velocity  and  of  pressure  with  every  discharge 
of  the  ventricle,  and  although  this  variation  is  absent  from  the 
veins,  since  normally  the  pulse,  due  to  the  ventricular  discharge, 
does  not  penetrate  into  them,  the  venous  flow  is,  nevertheless,  as  a 
matter  of  fact,  more  irregular  than  the  arterial.  So  that  if  it  is 
difficult  to  give  a  useful  definition  of  the  term  '  velocity  of  the 
blood  '  in  the  case  of  the  arteries,  it  is  still  more  difficult  to  do  so  in 
the  case  of  the  veins.  Where  voluntary  movement  is  prevented, 
one  potent  cause  of  variation  in  the  venous  flow  is  ehminated;  and 
in  curarized  animals  certain  observers  have  found  but  little  differ- 
ence between  the  mean  velocity  in  the  veins  and  in  the  corre- 
sponding arteries.  Others  have  found  the  velocity  in  the  veins 
considerably  less,  which  is  indeed  what  we  should  expect  from  the 
fact  that  the  average  cross-section  of  the  venous  system  is  greater 
than  that  of  the  arterial  system.  Burton-Opitz,  by  means  of  a 
stromuhr,  obtained  a  mean  velocity  of  147  mm.  per  second  in  the 
external  jugular  vein  of  a  13-kilo  dog. 

To  sum  up,  we  may  conclude  that,  upon  the  whole,  the  blood 
passes  with  gradually-diminishing  velocity  from  the  left  ventricle 
along  the  arteries ;  it  is  greatly  and  somewhat  suddenly  slowed  in  the 
broad  and  branching  capillary  bed;  but  the  stream  gathers  force 
again  as  it  becomes  more  and  more  narrowed  in  the  venous  channel, 
although  it  never  acquires  the  speed  which  it  has  in  the  aorta. 

Venous  Pulse. — To  complete  the  account  of  the  circulation  in  the 
veins,  it  may  be  recalled  that,  in  addition  to  the  venous  pulse 
described  on  p.  131,  which,  as  an  occasional  phenomenon,  may 
travel  through  widened  arterioles  and  capillaries  from  the  arteries 
into  the  veins,  and  therefore  in  the  direction  of  the  blood-stream, 
a  so-called  venous  pulse,  travelling  from  the  heart  against  the  blood- 
stream and  depending  on  variations  of  pressure  in  the  right  auricle, 
may  be  detected  in  the  jugular  veins  in  healthy  persons,  and  more 
distinctly  in  certain  disorders  of  the  circulation,  where  indeed  it 
may  be  evident  at  a  greater  distance  from  the  heart — for  example, 
over  the  liver  as  the  so-called  liver  pulse.  In  animals  a  venous 
pulse  of  this  nature  has  been  demonstrated  in  the  venae  cavae,  the 
jugular  vein,  and  with  a  dehcate  manometer  even  in  the  large  veins 
of  the  limbs.  It  moves  with  a  speed  of  i  to  3  metres  a  second 
(Morrow).  It  is  most  easily  observed  in  the  jugular  veins  in  man, 
because  of  their  proximity  to  the  heart.  We  have  already  pointed 
out  the  significance  of  the  study  of  this  venous  pulse  for  the  analysis 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS      135 

of  cardiac  events  (p.  100).  A  jugular  venous* pulse  of  a  perfectly 
different  origin  is  seen  in  cases  of  incompetence  of  the  tricuspid 
valve.  Here  the  chief  elevation  is  synchronous  with  the  ventricular 
systole,  and  is  caused  by  the  regurgitation  of  blood  from  the  right 
ventricle  through  the  auricle  into  the  veins.  The  so-called  '  com- 
municated venous  pulse  '  is  simply  due  to  the  proximity  of  some 
large  artery,  especially  when  enclosed  in  a  common  sheath,  whose 
pulsations  are  directly  transmitted  to  the  vein.  The  changes  of 
pressure  in  the  great  veins  accompanying  the  respiratory  move- 
ments (p.  284)  are  also  sometimes  spoken  of  as  a  venous  pulse,  but 
they  are  produced  in  a  different  way — namely,  by  the  rhythmical 
alteration  in  the  intrathoracic  pressure,  which  alternately  favours 
and  hinders  the  venous  return  to  the  heart. 

The  Circulation-Time. — Hering  was  the  first  who  attempted  to 
measure  the  time  required  by  the  blood,  or  by  a  blood-corpuscle,  to 
complete  the  circuit  of  the  vascular  system.  He  injected  a  solution  of 
potassium  ferrocyanide  into  a  vein  (generally  the  jugular),  and  collected 
blood  at  intervals  from  the  corresponding  vein  of  the  opposite  side. 
After  the  blood  had  clotted,  he  tested  for  the  ferrocyanide  by  addition 
of  ferric  chloride  to  the  serum.  The  first  of  the  samples  that  gave  the 
Prussian  blue  reaction  corresponded  to  the  time  when  the  injected  salt 
had  just  completed  the  circulation.  This  method  was  improved  by 
Vierordt,  who  arranged  a  number  of  cups  on  a  revolving  disc  below  the 
"/ein  from  which  the  blood  was  to  be  taken.  In  these  cups  samples  of 
the  blood  were  received,  and  the  rate  of  rotation  of  the  disc  being  known, 
it  was  possible  to  measure  the  interval  between  the  injection  and  appear- 
ance of  the  salt  with  considerable  accuracy.  Hermann  made  a  further 
advance  by  allowing  the  blood  to  play  upon  a  revolving  drum  covered 
with  paper  soaked  in  ferric  chloride,  and  by  using  the  less  poisonous 
sodium  ferrocyanide  for  injection. 

Even  as  thus  modified,  the  method  laboured  under  serious  defects. 
It  was  not  possible  to  make  more  than  a  single  obser\'ation  on  one 
animal,  at  least  without  allowing  a  considerable  interval  for  the  elimina- 
tion of  the  ferrocyanide,  and,  further,  the  method  was  unsuited  for  the 
estimation  of  the  circulation-time  in  individual  organs.  In  both  of 
these  respects  the  more  recently  introduced  electrical  method  presents 
considerable  advantages;  for  by  its  aid  we  can  not  only  obtain  satis- 
factory measurements  of  the  circulation-time  in  such  organs  as  the 
lungs,  liver,  kidney,  etc.,  but  we  can  repeat  them  an  inde finite  number 
of  times  on  the  same  animal. 

A  cannula,  connected  with  a  burette  (or  a  Mariotte's  bottle,  or  a 
syringe),  containing  a  solution  of  sodium  chloride  (usually  a  i'5  to 
2  per  cent,  solution),  is  tied  into  a  vessel — say  the  jugular  vein.  Sup- 
pose that  the  time  of  the  circulation  from  the  jugular  to  the  carotid  is 
required — that  is,  practically  the  time  of  the  lesser  or  pulmonary-  circu- 
lation. A  small  portion  of  one  carotid  artery  is  isolated,  and  laid  on 
a  pair  of  hook-shaped  platinum  electrodes,*  covered,  except  on  the 
concave  side  of  the  hook,  with  a  layer  of  insulating  varnish.  To 
further  secure  insulation,  a  bit  of  very  thin  sheet-indiarubbcr  is  slipped 
between  the  artery  and  the  tissues.     By  means  of  the  electrodes  the 

*  The  electrodes  can  easily  be  made  by  beating  out  one  end  of  a  piece  of 
thick  platinum  wire  to  a  breadth  of  3  or  6  mm.,  and  then  bending  the  flattened 
part  into  a  hook,  or  by  bending  pieces  of  stout  platinum  foil. 


136 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


piece  of  artery  lying  ^between  them,  with  the  blood  that  flows  in  it,  is 
connected  up  as  one  of  the  resistances  in  a  Wheatstone's  bridge  (p.  699). 
The  secondary  coil  of  a  small  inductorium,  arranged  for  giving  an  inter- 
rupted current,  and  with  a  single  Daniell  or  dry  cell  in  its  primary,  is 
substituted  for  the  battery,  and  a  telephone  for  the  galvanometer, 
according  to  Kohlrausch's  well-known  method  for  the  measurement  of 
the  resistance  of  electrolytes.  It  is  well  to  have  the  induction  machine 
set  up  in  a  separate  room  and  connected  to  the  resistance-box  by  Ijng 
wires,  so  that  the  noise  of  the  Neef's  hammer  may  be  inaudible.  The 
bridge  is  balanced  by  adjusting  the  resistances  until  the  sound  heard 
in  the  telephone  is  at  its  minimum  intensity,  the  secondary  coil  being 
placed  at  such  a  distance  from  the  primary  that  there  is  no  sign  of 
stimulation  of  muscles  or  nerves  in  the  neighbourhood  of  the  electrodes 


TKC-rvnoinC'i 


Fig.  61. — Measurement  of  the  Pulmonary  Circulation-Time  in  Rabbit  by  Injection 
of  Methylene  Blue. 

when  the  current  is  closed.  A  definite,  small  quantity  of  the  salt  solu- 
tion is  now  allowed  to  run  into  the  vein  by  turning  the  stop-cock  of  the 
burette.  It  moves  on  with  the  velocity  of  the  blood,  and  reaching  the 
artery  on  the  electrodes  causes  a  diminution  of  its  electrical  resistance 
(p.  26).  This  disturbs  the  balance  of  the  bridge,  and  the  sound  in  the 
telephone  becomes  louder.  The  time  from  the  beginning  of  the  injec- 
tion to  the  alteration  in  the  sound  is  the  circulation  -  time  between 
jugular  and  carotid.  It  can  be  read  off  by  a  .stop-watch,  or  more 
accuratelj'  by  an  electric  time-maker  writing  on  a  revolving  drum 
(Fig.  62).  Instead  of  the  telephone  a  galvanometer  may  be  used,  the 
equal  and  oppositely  directed  induction  shocks  being  replaced  by  a 
weak  voltaic  current,  and  the  platinum  by  unpolarizable  electrode^ 
(p.  705).     But  this  is  less  convenient. 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS     137 

The  circulation-time  of  an  organ  like  the  kidney  can  be  measured  by 
adjusting  a  pair  of  electrodes  under  the  renal  artery  and  another  under 
the  renal  vein,  and  reading  ofl  the  interval  required  by  the  salt  solution 
to  pass  from  the  point  of  injection  first  to  the  artery  and  then  to  the 
vein.     The  difference  is  the  circulation-time  through  the  kidney. 

For  certain  purposes,  and  particularly  for  measurements  on  small 
animals  like  the  rabbit,  or  on  organs  whose  vessels  are  too  delicate  to 
be  placed  on  electrodes  without  the  risk  of  serious  interference  with 
the  circulation,  another  method  may  be  employed  with  advantage.  It 
depends  on  the  injection  of  a  pigment,  like  methylene  blue,  which  at 
first  overpowers  the  colour  of  the  blood  and  shows  through  the  walls  of 
the  bloodvessels,,  but  is  soon  reduced  to  a  colourless  substance  (Fig.  61). 
The  details  of  the  method  are  given  in  the  Practical  Exercises  (p.  217.) 

It  may  be  said  in  general  terms  that  in  one  and  the  same  animal 
the  time  of  the  lesser  circulation  is  short  as  compared  with  the  total 
circiilation-time,  relatively  constant,  and  but  little  affected  by  changes 
of  temperature.  In  animals  of  the  same  species  it  increases  with  the 
size,  but  more  slowly,  and  rather  in  proportion  to  the  increase  of 
surface  than  to  the  increase  of  weight. 

Thus  a  dog  weighing  2  kilogrammes  had  an  average  pulmonary 
circulation-time  of  4'05  seconds,  while  that  of  a  dog  weighing  11 '8  kilos 
was  8*7  seconds,  and  that  of  a  dog  with  a  body-weight  of  18*2  kilos  only 
io*4  seconds.  It  is  probable  that  in  a  man  the  pulmonary  circulation- 
time  is  not  usually  much  less  than  12  seconds,  nor  much  more  than 
15  seconds. 

The  circulation-time  in  the  kidney,  spleen  and  hver  is  relatively 
long  and  much  more  variable  than  that  of  the  lungs,  being  easily 
affected  by  exposure  and  changes  of  temperature  (increased  by 
cold,  diminished  by  warmth). 

In  a  dog  of  13-3  kilos  weight  the  average  circulation-time  of  the 
spleen  was  10-95  seconds;  kidney,  13-3  seconds;  lungs,  8-4  seconds. 
The  circulation-time  of  the  stomach  and  intestines  is  (in  the  rabbit) 
comparatively  short,  not  exceeding  very  greatly  that  of  the  lungs, 
but  it  is  lengthened  by  exposure.  The  circulation-time  of  the 
retina  and  that  of  the  heart  (coronary  circulation)  are  the  shortest 
of  all. 

The  total  circulation-time  is  properly  the  time  required  for  the  whole 
of  the  blood  to  complete  the  round  of  the  pulmonary  and  systemic 
circulation.  But  there  are  many  routes  open  to  any  given  particle  of 
blood  in  making  its  systemic  circuit.  If  it  passes  from  the  aorta  through 
the  coronary  circulation  it  takes  an  exceedingly  short  route.  If  it  passes 
through  the  intestines  and  liver,  or  through  the  kidney,  or  through  the 
lower  limbs,  it  takes  a  long  route.  So  that  to  determine  the  total  cir- 
culation-time by  direct  measurement  we  must  know  (i)  the  quantity 
of  blood  that  passes  on  the  average  by  each  path  in  a  given  time,  and 
(2)  the  average  circulation-time  of  each  path.  If  the  average  weight  of 
blood  in  each  organ  be  represented  by  vOi,  w^,  w^,  etc. ;  and  the  average 
circulation-times  by  t^,  t^,  is,  etc. ;  and  t  be  the  total  systemic  circulation. 

t  t  t 

time;  then  w.,  ,  w.,    ,  w^    ,  etc.,  will  represent  the  quantity  of  blood 

*i        '^2  '3 

passing  through  each  organ  in  -  seconds,  since  in  the  average  circuit- 


138 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


tion-time  of  an  organ  the  whole  of  the  blood  in  it  at  the  beginning  of 
the  period  of  observation  will  have  been  exchanged  for  fresh  blood. 
But  the  whole  of  the  blood  in  the  body,  which  we  may  call  W,  passes 
once     round     the     systemic     circulation     in     t     seconds.       Therefore, 

j£,   -  _l_j^ \-w^—,  etc.,=W.     In  this  equation  everything  can  be  de. 

termined  by  experiment  except  t,  and  therefore  /  can  be  calculated. 
Adding  t  to  the  puhnonary  circulation -time,  we  arrive  at  the  tota 
circulation -time . 

Although  our  experimental  data  are  as  yet  too  meagre  to  make  the 
calculation  more  than  a  rough  approximation,  it  appears  probable  that 
in  certain  animals  the  total  circulation-time  is  five  or  six  times  as  great 
as  the  pulmonary  circulation-time.  If  the  same  ratio  holds  good  in 
man,  the  total  circulation-time  is  unlikely  to  be  much  less  than  a  minute 

or  much  greater  than  a 


T. 


j_jLjijui-n-jLJiJi_a-aJLJLJLAJi_n_^^ 


mmute  and  a  quarter. 
We  shall  see  directly 
that  this  estimate  is 
confirmed  by  data  de- 
rived from  a  different 


In  the  mean- 
may   use   it 


u 


JUlJl_ILJlJlJLJLAJlJUl-n_nJULJlJL^ 


m 


source, 
time,    we 

f)rovisionally  to  calcu 
ate  the  work  done  by 
the  heart.  Let  us  take 
for  simplicity  the  total 
circulation  -  time  as  i 
minute  in  a  70 -kilo 
man,  the  quantity  of 
blood  as  4^  kilos,*  and 
the  mean  pressure  in 
the  aorta  as  150  mm. 
of  mercury.  Up  to  the 
time  when  the  semi- 
lunar valves  are  opened, 
the  work  done  by  the 
left  ventricle  is  spent 
in  raising  the  intraven- 
tricular pressure  till  it 
is  sufficient  to  over- 
come the  pressure  in 
the  aorta.  If  a  vertical 
tube  were  connected 
with  the  left  ventricle, 
the  blood  would  rise  till 
the  column  was  of  the  same  weight  as  a  column  of  mercury  of  equal  section 
and  150  mm.  high.  This  column  of  blood  would  be  about  192  metres  in 
height.  If  a  reservoir  were  placed  in  communication  with  the  tube  at 
this  height,  a  quantity  of  blood  equal  to  that  ejected  from  the  ventricle 
would  at  each  systole  pass  into  the  reservoir;  and  the  work  which  the 
blood  thus  collected  would  be  capable  of  doing,  if  it  were  allowed  to 
fall  to  the  level  of  the  heart,  would  be  equal  to  the  work  expended  by 
the  heart  in  forcing  it  up.  Thus,  in  i  minute  the  work  of  the  left  ven- 
tricle would  be  equal  to  that  done  in  raising  4^  kilos  of  blood  to  a  height 

*  The  mean  of  the  5^  kilos  given  by  most  writers,  and  of  the  3J  kilos  gb' 
tained  by  Haldane  and  Smith  (p.  56). 


_JLJl_JLJLJLJLJl_n-JLJl_JLJLJUULJL^^ 

Fig.  62. — Time  of  the  Lesser  Circulation.  Cat  anaes- 
thetized with  Ether.  Time-trace,  seconds.  The  line 
above  the  time-trace  was  written  by  an  electro- 
magnetic signal,  the  circuit  of  which  was  closed  at 
the  moment  when  injection  of  methylene  blue  into 
the  jugular  vein  was  begun,  and  opened  at  the 
moment  when  the  change  of  colour  in  the  carotid 
was  observed.  I,  normal  circulation-time;  II,  cir- 
culation-time after  section  of  both  vagi  (much 
diminished);  III,  circulation-time  during  stimulation 
of  the  peripheral  end  of  one  vagus  (much  increased). 


MECHANICS  OF  THE  CIRCULATION  IN  THE   VESSELS       139 

of  I '92  metres — that  is,  about  864  kilogramme-metres;  in  24  hours  it 
would  be,  say,  12,450  kilogrammc-mctrcs.  Taking  the  mean  pressure 
in  the  pulmonary  artery  at  one-third  ot  the  aortic  pressure,  we  get  for 
the  daily  work  of  the  right  ventricle  about  4,150  kilogramme -metres. 
The  work  of  the  two  ventricles  is  thus  about  16,600  kilogramme-metres,* 
which  is  enough  to  raise  a  weight  of  nearly  4  pounds  from  the  bottom 
of  the  deepest  mine  in  the  world  to  the  top  of  its  highest  mountain,  or 
to  raise  the  man  himself  to  1^  times  the  height  of  the  spire  of  Strasburg 
Cathedral,  or  twice  the  height  of  the  loftiest  '  skyscraper  '  in  New  York. 
By  friction  in  the  bloodvessels  this  work  is  almost  all  changed  into  its 
equivalent  of  heat,  nearly  40,000  gramme-calories  (p.  663) .  Further,  since 
the  contraction  of  the  heart  is  always  maximal  (p.  154),  and  there  is 
reason  to  believe  that  the  quantity  of  blood  ejected  at  a  single  systole 
by  the  left  ventricle  (being  dependent  upon  the  inflow  from  the  pulmon- 
ary veins,  and  therefore  upon  the  inflow  into  the  right  side  of  the  heart 
from  the  systemic  veins)  varies  widely,  some  of  the  mechanical  effect 
of  the  contraction  must  be  wasted  when  the  quantity  is  less  than  the 
ventricle  is  capable  of  expelling. 

Output  of  the  Heart. — If  4J  kilos  of  blood  pass  through  the  heart  in 
I  minute  with  the  average  pulse-rate  of  72  per  minute,  the  quantity 

ejected  by  either  ventricle  with  every  systole  will  be  — —  =  62-5  grm., 

72 

or  a  little  less  than  60  c.c.  The  output  may  be  expressed  in  grammes 
or  cubic  centimetres  per  minute  (the  minute  volume),  or  per  second,  or 
per  beat.  It  has  been  measured  in  animals  in  several  ways — e.g.,  by 
inserting  a  stromuhr  (p.  121)  on  the  course  of  the  aorta,  or  by  recording 
the  variations  in  the  volume  of  the  heart,  or,  better,  of  the  ventricles, 
by  means  of  a  plethysmograph  (cardiometer  of  Henderson),  in  which 
the  organ  is  enclosed.  Another  method,  which  does  not  entail  the 
opening  of  the  chest,  is  to  allow  a  salt  solution  to  run  slowly,  for  a  de- 
finite number  of  seconds,  into  the  left  ventricle  through  a  tube  passed 
into  it  from  the  carotid  artery.  A  sample  of  the  mixture  of  blood  and 
salt  solution  is  collected  from  a  branch  of  the  femoral  artery,  where  its 
arrival  is  detected  by  the  change  of  electrical  resistance  (p.  135).  From 
the  amount  of  salt  solution  which  must  be  added  to  a  normal  sample 
of  blood  drawn  before  the  injection  to  make  its  conductivity  the  same 
as  that  of  the  sample  taken  during  the  passage  of  the  mixture,  the 
quantity  of  blood  with  which  the  solution  was  mixed  in  the  ventricle 
during  the  injection  can  be  approximately  determined.  By  this  method 
it  has  been  shown  in  a  series  of  experiments  on  more  than  twenty  dogs, 
ranging  in  weight  from  5  to  nearly  35  kilos,  that  the  output  of  the 
left  ventricle  per  kilo  of  body-weight  per  second  diminishes  as  the  size 
of  the  animal  increases;  and  the  relation  between  body-weight  and  out- 
put is  such  that  in  a  man  weighing  70  kilos  we  can  hardly  suppose  that 
the  ventricle  discharges,  during  bodily  rest,  more  than  105  grm.  of 
blood  per  second,  or  87  grm.  (80  c.c.)  per  heart-beat  with  a  pulse-rate 
of  72.  Putting  this  result  along  with  that  deduced  from  the  circulation- 
time,  we  can  pretty  safely  conclude  that  the  average  amount  of  blood 
thrown  out  by  each  ventricle  at  each  beat  is  not  more  than  70  or  80  c.c. 
Zuntz,  from  the  quantity  of  oxygen  absorbed  by  the  blood  in  the  lungs 
in  a  definite  short  time,  and  the  difference  between  the  oxygen  content 
of  samples  of  the  arterial  and  venous  blood,  has  estimated  the  output 
per  beat  at  60  c.c.     But  according  to  him  this  may  be  doubled  during 

•  Since  the  blood  on  expulsion  is  moving  with  a  certain  velocity,  an  addi- 
tion might  be  made  for  its  kinetic  energy.  But  this  would  only  increase  the 
total  work  by  a  small  fraction  (about  i  per  cent.). 


I40  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

severe  muscular  work,  when,  as  a  matter  of  fact,  by  the  aid  of  the 
Rontgen-rays  or  by  percussion  of  the  chest,  the  volume  of  the  heart 
may  be  shown  to  be  considerably  increased.  Tigerstedt,  on  the  basis 
of  stromuhr  measurements  in  animals,  puts  the  ventricular  output  per 
beat  in  man  at  50  to  100  c.c. ;  Plesch,  on  the  basis  of  gasometric  ob- 
servations on  man,  at  59  c.c.  Recently  Krogh,  using  a  gasometric 
method  based  on  the  absorption  of  nitrous  oxide  gas  in  the  lungs,  found 
that  the  minute  volume  during  rest  may  vary  between  wide  limits 
(2-8  to  8'7  Utres  of  blood  per  minute,  corresponding,  with  a  pulse-rate 
of  70,  to  40  c.c.  to  120  c.c.  per  beat).  During  muscular  work  there  is 
a  great  and  immediate  increase,  up  to,  it  may  be,  21-6  litres  per  minute. 
These  great  variations  in  the  output  of  the  ventricle  depend  primarily 
upon  variations  in  the  rate  of  return  of  the  blood  to  the  heart  by  the 
veins.  According  to  Henderson,  however,  such  great  variations  in  the 
output  per  beat  as  are  postulated  by  the  majority  of  physiologists  who 
have  worked  at  the  subject  do  not  occur,  and  the  fundamental  variable 
is  the  rate  of  the  beat. 

In  healthy  persons  in  whom  the  pulse-rate  is  permanently  much 
below  the  normal  (p.  107)  the  output  of  the  ventricle  per  beat  must,  of 
course,  be  correspondingly  increased.  In  a  man  with  a  pulse -rate 
always  below  40  during  rest  in  the  sitting  position,  the  flow  in  the  hands 
was  found  to  be  normal  in  amount,  and  all  the  signs  of  a  normal  delivery 
of  blood  from  the  left  ventricle  were  present.  Here  the  output  per 
beat  must  have  been  twice  the  usual  amount  during  rest. 


Section  IV. — The  Heart-Beat  in  its  Physiological 
Relations. 

So  far  we  have  been  considering  the  circulation  as  a  purely 
physical  problem.  We  have  spoken  of  the  action  of  the  heart  as 
that  of  a  force-pump,  and  perhaps  to  a  small  extent  that  of  a  suction- 
pump  too.  We  have  spoken  of  the  bloodvessels  as  a  system  of  more 
or  less  elastic  tubes  through  which  the  blood  is  propelled.  We  have 
spoken  of  the  resistance  which  the  blood  experiences  and  the  pressure 
which  it  exerts  in  this  system  of  tubes,  and  we  have  considered  the 
causes  of  this  resistance,  the  interpretation  of  this  pressure,  and  the 
physical  changes  in  the  vascular  system  that  may  lead  to  variations 
of  both.  But  so  far  we  have  not  at  all,  or  only  incidentally  and  very 
briefly,  dealt  with  the  physiological  mechanism  through  which  the 
physical  changes  are  brought  about.  We  have  now  to  see  that, 
although  the  heart  is  a  pump,  it  is  a  living  pump ;  that,  although  the 
vascular  system  is  an  arrangement  of  tubes,  these  tubes  are  alive; 
and  that  both  heart  and  vessels  are  kept  constantly  in  the  most 
delicate  poise  and  balance  by  impulses  passing  from  the  central 
nervous  system  along  the  nerves. 

In  many  respects,  and  notably  as  regards  the  influence  of  nerves 
on  it,  we  may  look  upon  the  heart  as  an  expanded,  thickened  and 
rhythmically-contractile  bloodvessel,  so  that  an  account  of  its 
innervation  may  fitly  precede  the  description  of  vaso- motor  action 
in  general 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS     14I 

fhe  Relation  of  the  Heart  to  the  Nervous  System. — A  very  simple 
experiment  is  sufficient  to  prove  that  the  beat  of  the  heart  does  not 
depend  on  its  connection  with  the  central  nervous  system,  for  an 
excised  frog's  heart  may,  under  favourable  conditions,  of  which  the 
most  important  are  a  moderately  low  temperature,  the  presence  of 
oxygen,  and  the  prevention  of  evaporation,  continue  to  beat  for  days. 
The  mammalian  heart  also,  after  removal  from  the  body,  beats  for 
a  time,  and  indeed,  if  defibrinated  blood  be  artificially  circulated 
through  the  coronary  vessels,  for  several  or  even  many  hours.  But 
although  this  proves  that  the  heart  can  beat  when  separated  from 
the  central  nervous  system,  it  does  not  prove  that  nervous  influence 
is  not  essential  to  its  action,  for  in  the  cardiac  substance  nervous 
elements,  both  cells  and  fibres,  are  to  be  found. 

The  Intrinsic  Nerves  of  the  Heart, — In  the  heart  of  the  frog 
numerous  nerve-cells  occur  in  the  sinus  venosus,  especially  near  its 
junction  with  the  right  auricle  (Remak's  gangUon).  A  branch 
from  each  vagus,  or  rather  from  each  vago-sympathetic  nerve  (for 
in  the  frog  the  vagus  is  joined  a  little  below  its  exit  from  the  skull 
by  the  sympathetic),  enters  the  heart  along  the  superior  vena  cava 
(pp.  157,  196). 

Running  through  the  sinus,  with  whose  ganghon-cells  the  true  vagus 
fibres,  or  some  of  them,  are  believed  to  make  physiological  junction 
(p.  163),  the  nerves  pursue  their  course  to  the  auricular  septum.  Here 
they  form  an  intricate  plexus,  studded  with  ganglion-cells.  From  the 
plexus  ii.erve-fibres  issue  in  two  main  bundles,  which  pass  down  the 
anterior  and  posterior  borders  of  the  septum  to  end  in  two  clumps  of 
nerve-cells  (Bidder's  ganglia),  situated  at  the  auriculo-ventricular 
groove.  These  ganglia  in  turn  give  off  fine  nerve-bundles  to  the  ven- 
tricle, which  form  three  plexuses — one  under  the  pericardium,  another 
under  the  endocardium,  and  a  third  in  the  muscular  wall  itself,  or  myo- 
cardium. From  the  last  of  these  plexuses  numerous  non-medullated 
fibres  run  in  among  the  muscular  fibres  and  end  in  close  relation  with 
them.  Similar  plexuses  of  nerve-fibres  exist  in  the  mammalian  ventricle. 
But  while  scattered  ganglion-cells  are  found  in  the  upper  part  of  the 
ventricular  wall,  most  observers  have  been  unable  to  demonstrate  any 
either  in  the  mammal  or  the  frog  in  the  apical  half.  In  the  rat's  heart, 
according  to  the  careful  observations  of  Schwartz,  true  ganglion-cells 
are  confined  to  an  area  on  the  posterior  surface  of  the  auricles,  lying 
always  under  the  visceral  pericardium.  Other  writers,  however,  have 
stated  that  ganglion -cells  do  exist  in  the  apex  both  of  the  cat's  and  of 
the  frog's  heart.  In  connection  with  the  whole  question  it  must  be 
borne  in  mind  that  in  other  organs  improved  histological  methods  have 
brought  typical  nerve-cells  to  light  in  situations  where  they  were  not 
suspected  or  were  denied  to  exist,  and,  further,  that  all  investigators 
are  not  agreed  upon  the  histological  criteria  by  wliich  ganglion-ccUs  arc 
to  be  distinguished. 

Cause  of  the  Rhythmical  Beat  of  the  Heart. — Scarcely  any  physio- 
logical question  has  excited  greater  interest  for  many  years  than  the 
mechanism  of  the  heart-beat.  Several  properties  of  the  cardiac 
tissue  ought  to  be  distinguished  in  discussing  this  question:  (i)  Its 


142  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

automatism — i.e.,  its  power  of  beating  in  the  absence  of  external 
stimuli;  (2)  its  rhythmicity — i.e.,  its  power  of  responding  to  con- 
tinuous stimulation  by  a  series  of  rhythmically  repeated  contrac- 
tions; (3)  its  conductivity — i.e.,  its  power  of  conducting  the  contrac- 
tion wave  or  the  impulse  to  contraction  once  it  has  been  set  up;  and 
(4)  the  power  of  co-ordination,  in  virtue  of  which  the  various  parts 
of  the  heart  beat  in  a  regular  sequence. 

The  excitability  of  the  cardiac  tissue — that  is,  its  power  of  appro- 
priate response  (namely,  by  contraction)  to  a  suitable  stimulus — 
does  not  particularly  concern  us  here,  since  it  is  in  no  wise  a  property 
special  to  the  heart.  Only,  as  we  shall  see  in  the  sequel,  the  time- 
relations  of  this  excitability  are  of  interest,  for  the  existence  of  a 
refractory  period — that  is,  an  interval  during  which  the  cardiac 
muscle  refuses  to  respond  to  excitation — throws  light  upon  the 
rhythmicity  of  the  heart-beat.  The  tonicity  of  the  heart — i.e.,  its 
power  of  remaining  contracted  to  a  certain  extent  in  the  intervals 
between  successive  beats — is  another  property  of  great  importance 
in  certain  aspects,  but  which  only  needs  to  be  mentioned  at  present. 

Automatism  of  the  Heart-Beat — ^Neurogenic  and  Myogenic  H5rpo- 
theses. — That  the  heart-beat  is  automatic  is  sufficiently  shown  by 
the  fact  that,  as  already  mentioned,  an  excised  and  empty  heart 
will  go  on  beating  for  a  time,  for  many  hours  or  even  for  days  in  the 
case  of  cold-blooded  animals.  When  blood,  or  even  a  suitable 
solution  of  such  inorganic  salts  as  exist  in  serum,  is  caused  to  circu- 
late through  the  coronary  vessels  of  the  excised  heart  of  a  warm- 
blooded animal,  it  also  continues  to  contract  for  a  long  time.  In 
trying  to  understand  the  real  significance  of  the  automatic  beat  of 
the  heart,  physiologists  have  endeavoured,  first,  to  compare  different 
portions  of  the  heart  as  regards  the  degree  in  which  they  possess  this 
property  of  automaticity;  and,  second,  to  associate,  if  possible,  one 
or  other  of  the  active  tissues  that  compose  the  organ,  muscle,  and 
nervous  tissue,  with  this  characteristic  property.  It  cannot  be 
pretended  that  a  final  answer  to  this  question  is  possible  at  present. 
Nor  is  the  historical  controversy  which  it  has  occasioned  perhaps  as 
important  in  itself  as  the  space  usually  devoted  to  it  in  textbooks 
might  imply.  Yet  it  is  probable  that  the  series  of  fundamental 
facts  in  the  physiology  of  the  heart  elicited  in  the  long  discussion  can 
be  best  presented,  even  for  the  purposes  of  the  elementary  student, 
as  they  were  originally  brought  forward  in  the  form  of  pros  and 
cons,  of  arguments  for  and  against  the  neurogenic  or  the  myogenic 
hypothesis.  There  is  good  evidence  that  as  in  the  amphibian 
heart  the  contraction  starts  in  the  sinus  venosus,  so  in  the  mam- 
malian heart  it  starts  in  the  sinus  tissue  of  the  right  auricle  in  the 
region  of  the  sino-auricular  node.  Attempts  have  been  made  to 
demonstrate  that  the  origination  of  the  impulses  which  are  after- 
wards conducted  to  all  parts  of  the  heart  is  normally  confined  to 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      143 

the  node  itself,  and  the  sino-auricular  node  is  by  some  authors 
denominated  the  pace-maker  of  the  heart,  the  tissue  which  sets  the 
pace  for  the  rest  of  the  organ  and  gives  the  time  to  auricles  and 
ventricles  alike.  The  experimental  results,  however,  are  by  no 
means  harmonious,  some  observers  finding  that  destruction  of  the 
region  of  the  node  causes  no  change  in  the  rate  of  the  heart-beat, 
others  that  the  beat  is  permanently  slowed.  But  even  were  we  in 
a  position  to  sharply  dehmit  a  given  region  of  the  heart  as  the  point 
at  which  the  strong  tendency  to  contraction  inherent  in  the  cardiac 
tissue  as  a  whole  first  breaks  into  an  actual  beat,  this  would  scarcely 
enable  us  to  decide  offhand  where  the  cause  of  the  automatism 
resides,  in  the  muscular  tissue  or  in  the  intrinsic  nervous  apparatus, 
because  in  nearly  all  animals  hitherto  investigated  the  muscular 
tissue,  ganglion-cells,  and  nerve- fibres  are  inseparably  intermingled. 
In  Limulus,  however,  the  horseshoe  or  king  crab,  the  cardiac 
ganglion-cells  are  collected  in  a  nerve-cord  running  longitudinally  in 
the  median  hne  along  the  dorsal  surface  of  the  segmented  heart,  and 


Fig.  63. — The  Heart  and  the  Heart  Nerves  of  Limulus:  Dorsal  View  (Carlson).  (The 
heart  is  figured  one-half  the  natural  size  of  a  large  specimen.)  aa.  Anterior 
artery;  la,  lateral  arteries;  In,  lateral  nerves;  mnc,  median  nerve-cord;  os,  ostia. 


sending  off  at  intervals  branches  to  two  lateral  cords,  and  also 
branches  which  enter  the  heart  muscle  directly  (Fig.  63).  When 
the  median  nerve-cord  is  removed,  as  can  be  done  without  injuring 
the  muscle,  the  heart  ceases  for  ever  to  beat  spontaneously.  It 
still  contracts  when  directly  stimulated,  mechanically  or  electrically, 
but  the  contraction  never  outlasts  the  stimulation.  The  automatic 
power  therefore  resides  in  the  nerve-cord  alone,  and  not  in  the 
muscle.  The  same  is  true  of  the  rhythmical  power,  for  excitation 
of  the  nerves  that  pass  from  the  median  cord  to  the  muscle  produces, 
'  not  a  rhythmical  scries  of  beats  in  the  resting,  and  an  acceleration 
of  the  rhythm  in  the  pulsating  heart,  but  a  tetanus  closely  resembling 
that  produced  in  skeletal  muscle  on  stimulation  of  a  motor  nerve  ' 
(Carlson).  Conduction  and  co-ordination  are  also  effected  in  this 
heart  through  the  nervous  mechanism,  and  essentially  through  the 
median  nerve-cord;  for  section  of  the  longitudinal  nerves  in  any 
segment  of  the  heart  abolishes  the  co-ordination  of  the  two  ends  of 
the  heart  on  either  side  of  the  lesion,  while  division  of  the  muscle 
in  any  segment  does  not  affect  the  co-ordination.  It  is  not  per- 
missible to  transfer  these  results  wholesale  to  higher  hearts,  and 


144         THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

especially  the  conclusions  as  to  rhythm,  conduction,  and  co-ordina- 
tion. Nevertheless  the  Limulus  heart  affords  one  absolutely  un- 
ambiguous example  of  a  heart  whose  rhythmical  beat  is  sustained 
by  nervous  impulses.  And  in  the  case  of  the  higher  animals  also 
facts  may  be  adduced  in  favour  of  the  neurogenic  origin  of  the  beat. 
The  isolated  auricular  appendices  of  the  mammahan  heart,  in  which 
no  ganghon-cells  have  been  found,  refuse  to  beat  spontaneously. 
If  in  the  frog  we  divide  the  sinus,  which  is  conspicuously  rich  in 
ganghon-cells,  from  the  lower  portion  of  the  heart,  it  continues  to 
pulsate.  A  fragment  from  the  base  of  the  ventricle  will  go  on 
contracting  if  it  includes  Bidder's  ganghon,  but  not  otherwise.  We 
cut  off  the  lower  two-thirds  of  the  frog's  ventricle,  the  so-called 
apex  preparation,  which  either  contains  no  ganglion-cells  or  is 
relatively  poor  in  them,  and  it  remains  obstinately  at  rest.  Further, 
if,  without  actually  cutting  off  the  apex,  we  dissever  it  physiologically 
from  the  heart  by  crushing  a  narrow  zone  of  tissue  midway  between 
it  and  the  auriculo- ventricular  groove,  we  abolish  for  ever  its  power 
of  spontaneous  rh3i:hmical  contraction.  The  frog  may  live  for 
many  weeks,  but  in  general  the  apex  remains  in  permanent  diastole. 
It  can  beicaused  to  contract  by  an  artificial  stimulus,  but  it  neither 
takes  part  in  the  spontaneous  contraction  of  the  rest  of  the  heart, 
nor  does  it  start  an  independent  beat  of  its  own. 

What  can  be  simpler  than  to  assume  that  the  sinus  beats  because 
it  has  numerous  ganglion-cells  in  its  walls,  and  that  the  apex  refuses 
to  beat  because  it  has  comparatively  few  or  none  ?  Could  we  pick 
out  the  nerve-cells  from  the  sinus,  without  injuring  the  muscular 
tissue,  as  easily  as  we  can  extirpate  the  median  nerve-cord  in 
Limulus,  we  may  well  suppose  that  it  would  lose  its  power  of  auto- 
matic contrat:tion.  And  although,  if  we  pursue  our  investigations 
a  little  farther,  facts  may  emerge  which  seem  to  contradict  the 
neurogenic  hypothesis,  the  contradiction  is  usually  only  apparent. 
Let  us  inquire,  for  instance,  what  happens  to  the  auricles  and  ven- 
tricle of  the  frog's  heart  when  the  sinus  is  cut  off.  The  answer  is 
that  as  a  rule,  while  the  sinus  goes  on  beating,  the  rest  of  the  heart 
comes  to  a  standstill,  in  spite  of  the  numerous  ganglion-cells  in  the 
auricular  septum  and  the  auriculo-ventricular  groove.  Not  only 
so,  but  if  the  ventricle  be  now  severed  from  the  auricles  by  a  section 
carried  through  the  groove,  it  is  the  former,  poor  in  nerve-cells 
though  it  be,  which  will  usually  first  begin  to  beat.  We  shall  again 
have  to  discuss  this  experiment  (p.  165).  It,  at  any  rate,  cannot  be 
interpreted  as  proving  that  the  automaticity  of  the  heart  does  not 
depend  upon  the  presence  of  ganglion-cells.  For  although  a  portion 
of  the  heart  rich  in  ganglion-cells  may,  under  the  circumstances 
mentioned,  refuse  for  a  time  to  beat,  there  is  good  evidence  that 
this  is  due  either  to  a  peculiar  condition  called  inhibition  into  which 
the  muscular  tissue  or  the  nerve-cells  of  the  lower  portions  of  the 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      145 

heart  have  been  thrown  by  the  first  section,  or  more  probably  to 
the  loss  of  the  accustomed  impulses  from  the  sinus  which  normally 
give  the  signal  for  the  auricular  contraction.  A  stronger  argument 
in  favour  of  the  myogenic  theory  is  the  fact  that  the  embryonic 
heart  beats  with  a  regular  rhythm  at  a  time  when  as  yet  no  ganglion- 
cells  have  settled  in  its  walls.  But  it  may  well  be  that  this  primitive 
automatic  power  of  the  cardiac  muscle,  absolutely  necessary  at  first, 
since  the  early  establishment  of  the  circulation  is  essential  for  the 
development  of  the  tissues  in  general  and  of  the  nervous  system  in 
particular,  falls  into  abeyance  when  the  intrinsic  cardiac  nervous 
mechanism  is  completed,  or  at  least  becomes  subordinated  to  the 
latter.  The  advocates  of  the  myogenic  theory  further  state  that 
the  isolated  bulbus  aortse  of  the  frog,  and  even  tiny  fragments  of  it, 
will  pulsate  spontaneously,  and  that  the  same  is  true  of  small 
portions  of  the  great  veins  which  open  into  the  sinus.  The  rhyth- 
mical contraction  of  the  veins  of  the  bat's  wing  has  also  been  con- 
sidered an  argument  in  favour  of  myogenic  automatism.  In  none 
of  these  cases,  however,  can  the  complete  absence  of  ganglion-cells 
be  considered  satisfactorily  demonstrated.  The  statement  that  a 
portion  of  the  apex  of  the  dog's  ventricle  continues  for  a  considerable 
time  to  beat  with  a  rhythm  of  its  own  when  connected  with  the  rest 
of  the  heart  by  nothing  but  its  bloodvessels  and  the  narrow  isthmus 
of  visceral  pericardium  and  connective  tissue  in  which  they  lie  has 
not  been  confirmed  by  all  observers.  But  even  if  it  be  accepted,  it 
can  hardly  be  used  as  a  decisive  argument  against  the  neurogenic 
theory  so  long  as  the  absence  of  ganglion-cells  from  such  a  ventricular 
strip  has  not  been  demonstrated. 

The  fact  that  under  the  influence  of  a  constant  stimulus  portions 
of  the  heart  can  be  made  to  beat  rhythmically  has  been  sometimes, 
though  erroneously,  brought  forward  as  evidence  of  myogenic 
automatism.  Thus  the  supposedly  ganglion-free  apex  of  the  frog's 
heart,  lifeless  as  it  seems  when  left  to  itself,  can  be  caused  to  execute 
a  long  and  faultless  series  of  pulsations  when  its  cavity  is  distended 
with  defibrinated  blood  or  serum,  or  certain  artificial  nutritive 
fluids,  or  even  physiological  salt  solution.  The  passage  of  a  constant 
current  through  the  preparation  may  also  start  a  regular  rhythm. 
But  apart  from  the  question  whether  nervous  elements  would  not 
be  subjected  to  the  constant  stimulus  impartially  with  the  muscular 
elements  (and  nerve-fibres,  at  any  rate,  are  acknowledged  to  be 
present),  the  beat  here  produced  ought  not  to  be  considered  as  an 
automatic  beat,  but  as  a  contraction  evoked  by  an  external  stimulus. 
Such  experiments,  in  fact,  throw  no  light  upon  the  automatism  of 
the  heart,  but  prove  clearly  its  rhythmicity — i.e.,  its  power  of 
responding  to  a  continuous  stimulus  by  regularly  recurring  con- 
tractions. While  we  are  hardly  at  present  in  a  position  to  dis- 
criminate sharply  between  the  influence  of  constant  stimulation 


145  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

upon  the  nervous  and  upon  the  muscular  elements  of  the  heart,  and 
certainly  not  in  a  position  to  deny  to  the  nervous  elements  the 
power  of  responding  to  such  stimulation  by  rhythmical  discharges, 
it  can  hardly  be  doubted  that  the  cardiac  muscle  itself  possesses 
rhythmical  power.  This  is  a  property  which  also  belongs  to  the 
smooth  muscle  of  such  tubes  as  the  ureter,  whose  rhythmical  con- 
traction is  affected  by  distension  much  as  that  of  the  heart  is,  and 
in  a  smaller  degree  even  to  ordinary  skeletal  muscle,  which  can 
contract  with  a  kind  of  rhythm  under  the  stimulus  of  a  certain 
tension  and  in  certain  saline  solutions.  But  just  as  the  primitive 
automatism  of  the  cardiac  muscle  may  have  become  subordinated 
in  the  course  of  development  to  the  automatism  of  the  nervous 
elements,  so  the  primitive  rhythmical  power  of  the  muscle  may  under 
ordinary  conditions  remain  in  abeyance  and  yet  be  capable  of 
asserting  itself  in  favourable  circumstances,  and  when  the  normal 
rhythmical  impulses  from  the  nervous  apparatus  are  withdrawn. 
In  any  case,  in  the  normally  beating  heart  the  opportunity  for  the 
exercise  of  the  rhythmical  power  of  the  muscle  does  not  arise,  at 
least  in  the  case  of  the  lower  portions  of  the  heart.  For^the  impulses 
which  (in  the  frog's  heart),  descending  from  the  sinus,  liberate  the 
contraction  of  the  auricles,  and  the  impulses  which,  descending 
from  the  auricles,  liberate  the  contraction  of  the  ventricle,  appear 
to  be  discrete,  and  not  continuous;  in  other  words,  the  lower  portions 
of  the  heart  do  not  receive  from  the  upper  portions  a  continuous 
stream  of  stimuli  to  which  they  respond  by  rhythmical  contractions, 
but  a  series  of  rhythmically  repeated  impulses,  each  of  which 
evokes  a  single  contraction.  One  of  the  best  proofs  of  this  is  that 
if  the  sinus  is  heated  the  ventricle  beats  much  more  rapidly  in 
unison  with  the  rapidly  beating  sinus  and  auricles,  while  if  the 
ventricle  itself  is  heated  no  change  takes  place  in  its  rhythm. 
Now,  if  the  ventricle  responds  to  a  constant  stimulus  by  rhythmical 
beats,  the  condition  of  the  ventricular  tissue  ought  to  affect  the  rate 
of  its  beat.  In  the  mammalian  heart,  too,  an  alteration  in  the 
temperature  of  a  definite  area  of  the  wall  of  the  right  auricle  lying 
between  the  mouths  of  the  venae  cavae  produces  a  change  in  the  rate 
of  the  whole  heart,  while  no  effect  is  caused  by  altering  the  tempera- 
ture of  any  other  portion  of  the  heart.  It  has  already  been  stated 
that  the  impulses  from  the  nerve-cord  which  maintain  the  rhythm 
in  the  Limulus  heart  are  also  discontinuous. 

Conduction  and  Co-ordination. — The  question  of  the  conduction 
of  the  excitation  over  the  heart  and  the  co-ordination  of  its  parts 
is  in  the  same  position  as  the  question  of  the  automatism  and 
rhythmicity.  In  the  horseshoe  crab,  as  already  remarked,  the 
mechanism  appears  to  be  a  nervous  one.  In  higher  hearts,  on  the 
other  hand,  facts  have  been  discovered  which  favour  each  of  the 
rival  hypotheses.     In  the  frog's  heart  the  prob  i.bility  that  the  con- 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      147 

traction  wave  is  propagated  from  fibre  to  fibre  of  the  muscle  without 
the  intervention  of  nerves  has  been  much  insisted  upon,  since  the 
muscular  tissue,  although  presenting  certain  variations  in  its 
character  in  the  different  divisions  of  the  heart  and  at  their  junctions, 
forms  a  practically  continuous  sheet  over  the  whole  organ  from 
base  to  apex.  In  support  of  this  view  has  been  brought  forward 
the  observation  that  the  delay  of  the  wave  at  the  auriculo- ventricu- 
lar groove  is  much  greater  than  it  ought  to  be  if  the  excitation  were 
transmitted  by  nerves,  since  the  velocity  of  the  nerve-impulse  is 
exceedingly  great  (p.  767) ;  and  the  further  observation  that,  when 
the  ventricle  is  caused  to  contract  by  artificial  stimulation  of  the 
auricle,  this  delay  is  appreciably  greater  when  the  stimulus  is  applied 
as  far  from  the  ventricle  as  possible  than  when  it  is  applied  as  near 
to  it  as  possible.  The  delay  has  been  attributed  to  the  '  embryonic  ' 
character  of  the  muscular  tissue  at  the  junction  of  the  sinus  with  the 
auricles  and  of  the  auricles  with  the  ventricles.  But  it  has  never 
been  demonstrated  that  muscular  fibres  with  the  histological  char- 
acters described  do,  as  a  matter  of  fact,  conduct  the  contraction 
wave  so  much  more  slowly  than  the  other  cardiac  muscular  fibres 
It  is  just  as  probable,  and  indeed  more  so,  that,  whether  the  con- 
traction travels  in  anj?-  particular  division  of  the  heart  directly  from 
muscle-fibre  to  muscle-fibre  or  not,  the  impulse  to  contraction  is 
transferred  from  each  division  of  the  heart  to  the  next  by  a  nervous 
mechanism  whose  action  is  timed  with  the  very  object  of  securing 
a  certain  interval  between  the  systoles  of  successive  divisions.  In 
any  case,  since  we  know  that  the  velocity  of  the  nerve-impulse  is 
very  different  in  difterent  varieties  of  nerves,  the  question  cannot  be 
decided  b}^  general  arguments  of  this  kind.  In  Limulus,  as  a  matter 
of  fact,  the  velocity  in  the  intrinsic  heart  nerves  is  only  one-tenth  as 
great  as  in  the  ordinary  motor  (Hmb)  nerves  of  the  animal  (Carlson). 
In  the  mammalian  heart  the  alleged  absence  of  muscular  con- 
nection between  the  auricles  and  ventricles  was  long  the  foundation 
of  the  general  belief  that  the  link  was  a  nervous  one.  Certainly 
there  is  no  dearth  of  nerves  which  might  serve  as  such  a  bridge. 
But  it  has  been  shown  (Kent,  His,  etc.)  that  in  the  mammahan 
heart,  too,  a  slender  band  of  muscular  fibres,  arising  at  a  definite 
point  (the  auriculo- ventricular  node)  near  the  coronary  sinus  on  the 
right  side  of  the  interauricular  septum  below  the  fossa  ovalis,  passes 
forwards  and  downwards  through  the  fibrous  ring  between  the 
auricles  and  ventricles  under  the  septal  cusp  of  the  tricuspid  valve. 
It  then  divides  into  two  branches,  one  for  each  ventricle,  which  run 
down  the  interventricular  septum  towards  the  apex,  spreading  out 
as  the  Purkinje  fibres  or  their  equivalent,  to  blend  at  last  with  the 
ordinary  muscle  of  the  ventricles,  and  particularly  of  the  inter- 
ventricular septum.  The  fibres  of  the  bundle  are  narrower  than  the 
other  fibres  of  the  auricles,  very  rich  in  nuclei,  and  only  slightly 


148 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


differentiated  into  fibrillae.  They  seem  to  represent  the  remains  of 
the  primitive  cardiac  tube,  which  by  the  development  of  certain 
pouches  and  twists  becomes  transformed  into  a  multi-chambered 
heart.  Their  resemblance  to  embryonic  fibres  suggests  that  they 
may  have  retained  the  primitive  capacity  of  the  mesodermic  tissue 
of  the  embryonic  heart  to  conduct,  and  even  to  originate,  the 
rhythmical  contraction.  But  while  there  is  no  decisive  evidence 
that  they  constitute  an  automatic  cardio-motor  centre,  as  some 
authors  have  supposed,  they,  or  at  least  the  narrow  bridge  of  tissue 
in  which  they  he,  do  play  an  important  part  in  the  conduction  of 
the  contraction  from  the  auricles  to  the  ventricles.     For  compres- 


Fig.  64. — Right  Auricle  and  Ventricle  of  Calf,  to  show  Auriculo-Ventricular  Band 
(Keith).  I,  central  cartilage;  2,  main  auriculo-ventricular  bundle;  3,  auriculo- 
ventricular  (A-V)  node;  4,  right  septal  division  of  the  bundle;  5,  moderator  band; 
6,  medial  or  septal  cusp  of  tricuspid  valve;  8,  coronary  sinus. 

sion  of  the  band  produces  a  block,  just  as  the  pressure  of  a  clamp 
in  the  auriculo-ventricular  groove  does  in  the  frog's  heart  (Kent). 
With  a  certain  degree  of  pressure  the  ventricle  beats  only  once  for 
two  beats  of  the  auricle,  with  greater  pressure  only  once  for  three 
or  more  auricular  beats.  With  a  still  greater  pressure  or  after 
crushing  or  section  of  the  bundle  conduction  is  abolished,  and  the 
ventricle  either  remains  at  rest  for  a  time,  as  in  the  frog's  heart,  or, 
what  is  much  more  common,  immediately  starts  beating  with  an 
independent  rhythm,  which  is  slower  than  that  of  the  auricles 
(Erlanger).  It  can  be  considered  certain  that  in  these  observations 
nerves  may  have  been  involved  in  the  block  as  well  as  the  muscle  of 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      149 

the  auriculo-ventricular  band,  since  this  band  is  richly  provided 
with  nerve-fibres  as  well  as  ganglion-cells  (Wilson).  Yet  it  is 
unlikely  that  all  the  nerves  capable  of  conducting  the  impulses  to 
contraction  should  be  gathered  into  such  a  narrow  compass,  and 
therefore  the  experiment  supports  the  view  that  the  conduction  is 


a       <v 


cb      a 


\ywAP\y\Vu^>\Ax\i 


Fig.  65.— Jugular  (Upper)  and  Carotid  (Lower)  Pulse-Tracing  from  a  Case  of  Arterio- 
sclerosis,  showing  Partial  Failure  of  Conduction  in  the  Auriculo-Ventricular 
Bundle  (Cushny  and  Grosh).  The  ventricle  only  beats  once  to  two  beats  of  the 
auricle.     Time-trace,  fifths  of  a  second. 

carried  out  in  the  muscular  tissue.  And  if  the  conduction  of  the 
fxcitation  from  auricles  to  ventricles  is  accomplished  by  a  muscular 
connection,  it  is  natural  to  suppose  that  the  co-ordination  of  sym- 
metrical portions  of  the  heart  on  either  side  of  the  loneritudinal  axis, 


Fig.  66. — Tracing  of  Jugular  (Upper)  and  Radial  (Lower)  Pulse  from  a  Man  with 
Heart-Block  (Lewis  and  Macnalty).  In  the  cycles  marked  34.  35.  and  36  the 
ventricular  contraction,  although  less  frequent  than  the  auricular,  was  initiated 
from  the  auricle.  In  the  last  two  cycles  (37  and  38)  and  the  pause  of  36  complete 
heart -block  wais  present.  On  the"  jugular  trace  the  a-c  interval  (representing 
the  interval  between  the  onset  of  the  auricular  and  ventricular  contractions)  is 
given,  and  on  the  radial  trace  the  duration  of  a  cardiac  cycle,  both  in  fifths  of  a 
second. 

the  co-ordination  in  virtue  of  which  the  two  auricles  contract 
together  and  the  two  ventricles  together,  is  also  achieved  by  the 
passage  of  impulses  through  the  muscular  tissue.  In  accordance 
with  this,  it  has  been  shown  that  the  ventricles  in  the  dog  and  cat 
continue  to  beat  in  unison,  after  the  attcn^.pt  has  been  made  to 


t5o  THE  CIRCULATION  OF  THE  BLOOD  A^D  LYMPH 

sever  any  nerves  connecting  them  by  extensive  zigzag  incisions,  so 
long  as  they  are  united  by  a  narrow  bridge  of  muscle  (Porter). 

In  disease,  interference  with  the  conduction  of  the  stimulus  from 
auricles  to  ventricles  along  the  atrio-ventricular  bundle  is  a  not  un- 
common phenomenon.  According  to  the  degree  of  interference,  the 
ventricular  contraction  may  be  simply  delayed,  or  only  a  certain  pro- 
portion of  the  auricular  contractions  (every  second,  every  third,  or 
every  fourth)  may  be  conducted  to  the  ventricle,  or,  finally,  the  block 
may  be  complete,  and  the  ventricle  then  contracts  quite  independently 
of  the  auricle,  the  stimulus  to  contraction  originating,  perhaps,  in  the 
uninjured  portion  of  the  bundle  below  the  seat  of  the  block.  These 
conditions  are  most  easily  recognized  by  comparing  tracings  simul- 
taneously obtained  from  the  jugular  vein  and  the  radial  artery  or  apex- 
beat  (p.  90).  When  the  block  is  complete  the  rate  of  the  ventricle  is 
very  slow  (about  30  in  the  minute,  or  less),  the  time  of  the  ventricular 
beat  is  clearly  unrelated  to  that  of  the  auricular,  and  the  stability  of 
the  ventricular  rhythm  is  abnormally  great,  such  circumstances  as 
usually  cause  a  marked  increase  in  the  pulse-rate- — mental  excitement, 
for  instance — affecting  it  little  or  not  at  all.     This  is  the  condition  in 


Fig.  67. — Polygraph  Tracing  fr  in  a  Case  of  True  Bradycardia  (Carter).     The  ower 
trace  is  the  radial,  the  upper  the  jugular.    Time-trace,  fifths  of  a  second. 

the  so-called  Stokes- Adams  disease.  In  some  of  these  cases  pathological 
(syphilitic)  changes  in  the  A-V  bundle  have  actually  been  discovered 
at  necropsy.  In  others  there  is  some  reason  to  believe  that  abnormal 
excitation  of  the  cardio-inhibitory  nerves  may  be  responsible  even  for 
long-continued  block,  especially  when  the  conductivity  of  the  bundle 
has  been  already  permanently  diminished. 

Cases  of  slow  heart  are  also  known  in  which  there  is  no  block  in 
the  conduction  system,  but  the  original  rhythm  of  the  auricle  is  slow 
(so-called  true  bradycardia,  Fig.  67). 

Kent  has  pointed  out  that  the  muscular  connection  between  the 
auricles  and  ventricles  is  not  single  and  confii.ed  to  the  A-V  bundle, 
but  multiple,  and  that  the  co-ordinated  action  of  the  chambers  of  the 
heart  is  to  some  extent  dependent  upon  the  integrity  of  muscular 
connections  other  than  that  which  exists  in  the  A-V  bundle.  One  of 
these  he  describes  as  the  '  right  lateral  connection,'  at  the  junction  of 
the  right  auricle,  the  right  ventricle,  and  the  tricuspid  valve,  at  the 
right-hand  margin  of  the  heart.  The  existence  of  this  additional  con- 
nection, the  importance  of  which  relatively  to  that  of  the  A-V  bundle 
need  not  be  the  same  in  every  heart,  may  explain  otherwise  puzzling 
results  both  clinical  and  experimental — e.g.,  that  sometimes  co-ordina- 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      151 

tion  between  the  ventricles  and  auricles  has  continued  after  destruction 
of  the  A-V  bundle,  while  sometimes  co-ordination  has  been  upset  by 
lesions  not  affecting  the  bundle. 

Fibrillary  Contraction. — In  the  case  of  the  warm-blooded  heart  a 
comp)letc  breakdown  of  co-ordination  occurs  under  certain  circum- 
stances, producing  the  phenomenon  known  as  fibrillary  contraction, 
or  delirium  cordis,  a  condition  in  which  each  minute  portion,  perhaps 
each  fibre,  of  the  whole  heart,  or  of  a  portion  of  it,  goes  on  contract- 
ing in  a  disorderly  manner,  quite  independently  of  the  rest.  The 
condition  is  often  seen  in  a  heart  that  has  been  exposed  for  some 
time,  particularly  in  the  ventricle,  and  can  be  induced  by  stimulating 
it  with  strong  induction  shocks  or  by  ligation  of  the  coronary 
arteries.  According  to  the  best  evidence,  the  condition  is  due  to 
the  fact  that  the  conductivity  of  the  fibrillating  muscle  is  interfered 
with  so  that  the  contraction  wave  is  prevented  from  running  its 
usual  course.  The  consequence  of  this  '  blocking  '  is  that  the 
normal  co-ordinated  action  of  the  musculature  gives  place  to  the 
confused  movement  characteristic  of  fibrillation  (Porter,  Garrey). 
There  is  no  reason  to  believe  that  fibrillary  contraction  is  connected 
with  the  loss  of  impulses  from  any  special  co-ordinating  centre,  for 
it  is  not  peculiar  to  the  heart,  but  is  typically  seen  in  the  tongue 
when  the  circulation  after  a  long  interruption  is  restored.  The 
peculiar  '  boiUng  '  movement  is  exactly  similar  to  that  observed  in 
the  heart,  probably  because  the  tongue  also  contains  fibres  running 
in  several  directions. 

The  confused  fibrillary  contractions  are  quite  ineffective  for  driving 
on  the  contents  of  the  heart.  Fibrillation  of  the  ventricle  is  therefore 
incompatible  with  life.  On  the  other  hand,  auricular  fibrillation,  far 
from  being  immediately  fatal,  is  one  of  the  most  common  of  the  chronic 
cardiac  disorders  in  man.  It  is  characterized  by  extreme  irregularity 
of  the  pulse,  due  to  the  fact  that  the  ventricles  are  played  upon  by  an 
irregular  stream  of  impulses  from  the  fibrillating  auricles  to  which  they 
respond  as  they  best  can.  The  auricular  wave  {a.  Figs.  65-67)  is  absent 
from  the  jugular  pulse-tracing,  and  the  P  wave  (Fig.  809),  corresponding 
to  the  electrical  change  produced  by  the  normally  contracting  auricles, 
is  absent  from  the  electrocardiogram.  Auricular  flutter  is  a  condition 
which  must  be  distinguished  from  auricular  fibrillation.  When  a  weak 
stimulus  is  applied  to  the  auricle  of  a  dog  or  cat,  the  auricular  beats  are 
greatly  increased  in  frequency  up  to  300  or  400  a  minute.  Although 
the  beats  are  so  rapid,  they  arc  otherwise  normal  beats.  When  the 
strength  of  the  stimulus  is  increased,  this  condition  of  flutter 
(MacWilliam)  passes  into  fibrillation.  Auricular  flutter  is  also  recog- 
nized clinically.  In  the  majority  of  cases  the  ventricle  docs  not  respond 
to  each  beat  of  the  auricle,  and  the  arterial  pulse  ia  irregular;  but  each 
aui-icular  contraction  produces  its  appropriate  effect  upon  the  electro- 
cardiogram and  often  also  upon  the  jugular  tracing  (Mackenzie). 

Without  entering  further  into  a  discussion  of  the  rival  hypotheses, 
we  may  sum  up  by  saying  that  for  one  heart  {that  of  Limulus)  the 
automatism  and  the  rhythmical  power  have  been  clearly  shoun  to  reside 


152  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

in  the  local  nervous  apparatus  ;  for  the  hearts  of  other  animals  full  and 
formal  proof  of  the  neurogenic  theory,  so  far  as  those  two  properties  of 
the  cardiac  tissue  are  concerned,  has  not  been  given.     It  is  probable, 
but  not  proven.     As  regards  the  conduction  and  co-ordination  of  the 
contraction,  the  bulk  of  the  evidence  {leaving  the  Limulus  heart  out  of 
account)  points  to  the  muscular  tissue  as  the  channel  through  which  the 
effective  impulses  pass.     The  normal  order  or  sequence  in  which  the 
different  parts  of  the  heart  contract  depends  upon  the  fact  that  the 
automatism  of  the  upper  portions  is  more  pronounced  than  that  of  the 
lower,  so  that  under  strictly  physiological  conditions  the  contraction  is 
only  propagated,  and  not  originated,  by  the  lower  parts  of  the  heart. 
When,  however,  the  signal  to  contraction  normally  given  by  the 
basal  region  is  prevented  from  reaching  the  lower  parts,  an  inde- 
pendent automatic  rhythm  of  the  latter  may  be  developed,  as  in 
the  case  of  the  mammalian  ventricle  mentioned  above.     Here  we 
may  suppose  that  the  automatic  mechanism  of  the  lower  portions 
of  the  heart  discharges  itself  as  soon  as  a  sufficient  accumulation  of 
energy  has  taken  place  in  it,  although  it  requires  a  longer  time  to 
reach  the  point  of  discharge  than  the  automatic  mechanism  of 
higher  parts,   and  therefore  is  normally  discharged  from  above. 
Under  certain  conditions  the  normal  sequence  can  be  reversed.  In  the 
heart  of  the  skate  it  is  easy,  by  stimulating  the  bulbus  arteriosus,  to 
cause  a  contraction  passing  from  bulbus  to  sinus.    The  power  of  pro- 
pagating the  contraction  may  also  be  artificially  altered.   As  already 
mentioned,  it  may  be  diminished  or  abolished  by  pressure.    The  same 
effect  may  be  produced  by  fatigue  or  cold,  while  heating  a  portion  of 
the  heart  in  general  increases  its  power  of  conducting  the  contraction. 
Chemical  Conditions  of  the  Beat. — When  we  have  localized  the 
essential  mechanism  of  the  rhythmical  beat  in  the  nervous  or  in  the 
muscular   elements,   the   question   may   still   be   asked   what   the 
chemical  and  physical  conditions  are  which  are  necessary  to  its 
maintenance.     While  it  is  known  that  a  supply  of  arterial  blood  at 
or  near  body-temperature,  and  under  a  sufficient  pressure,  is  required 
for  permanent   cardiac  contraction,   much  simpler   solutions  will 
suffice  to  maintain  the  activity  even  of  the  isolated  mammahan  heart 
for  a  considerable  time.    One  of  the  best  of  these  is  a  solution  contain- 
ing sodium  chloride,  potassium  chloride,  calcium  chloride,  and  sodium 
bicarbonate  in  the  proportions  in  which  they  exist  in  blood-serum, 
with  the  addition  of  a  small  quantity  of  dextrose  (Locke,  p.  66). 
When  this  solution,  properly  oxygenated  and  warmed,  is  circulated 
through  the  coronary  vessels  of  an  excised  rabbit's  or  cat's  heart, 
strong  and  regular  beats  may  be  observed  for  many  hours.     Some 
investigators  have  claimed  for  sodium  chloride,  and  even  for  sodium 
ions,  others  for  calcium  salts  or  calcium  ions,  a  special  role  in  the 
origination  or  maintenance  of  the  rhythmical  beat.     There  is  no 
doubt  that  strips  from  the  ventricle  of  the  tortoise  or  turtle,  which 


THE  HEART-BEAT  IN  ITS  PHYSIOLOGICAL  RELATIONS      153 

after  isolation  have  ceased  beating,  and  if  left  to  themselves  in  a 
moist  chamber  do  not  develop  rhythmical  contractions,  begin  after 
a  while  to  beat  when  immersed  in  or  irrigated  with  a  solution  of 
sodium  chloride  or  a  solution  of  cane-sugar  containing  a  little  of  that 
salt.  They  refuse  to  beat  in  any  solution  which  does  not  contain 
sodium  chloride  (Lingle).  The  addition  of  calcium  chloride  to  the 
sodium  chloride  solution,  or  preliminary  treatment  of  the  strip  with 
a  solution  of  a  calcium  salt  before  its  immersion  in  the  sodium 
chloride  solution,  hastens  the  onset  of  the  contractions,  and  increases 
the  length  of  time  for  which  they  are  kept  up  (Erlanger).  It  is 
unquestionable  that  for  the  normal  beat  of  the  heart  the  presence 
of  both  salts  is  one  of  the  necessary  conditions,  but  there  is  at 
present  no  sufficient  foundation  for  the  view  that  either  the  one  or 
the  other  acts  as  a  special  chemical  excitant  of  the  automatic 
contraction.  Still  less  necessary  is  it  to  make  this  assumption  for 
potassium.  Certain  potassium  salts  are,  of  course,  beneficial  to 
the  heart  as  to  other  tissues.  This  might  be  assumed  from  their 
presence  in  blood  and  lymph,  and  it  has  been  shown  experi- 
mentally. But  a  terrapin's  heart  will  continue  beating,  and  beating 
well  for  a  considerable  time  when  irrigated  with  a  solution  con- 
taining sodium  and  calcium  salts  alone  and  free  from  potassium. 
That  the  reaction  of  the  perfusive  fluid  is  of  great  importance  in 
connection  with  the  origination  of  rhythm  is  well  estabhshed,  and 
it  is  an  interesting  fact  that  the  limits  of  H  ion  concentration 
within  which  the  development  of  spontaneous  beats  is  possible 
differs  for  the  hearts  of  different  kinds  of  animals  (Mines),  and  even 
for  the  different  portions  of  the  frog's  heart  (Dale  and  Thacker). 
While  these  facts  illustrate  the  importance  of  the  inorganic  com- 
position of  the  nutritive  liquids  for  the  action  of  the  heart,  they 
leave  the  old  question  of  the  existence  and  the  nature  of  an  inner 
stimulus  to  the  rhythmic  contraction  very  much  where  it  was. 

Resuscitation  of  the  Heart. — Not  only  can  the  beat  of  the  freshly- 
excised  mammalian  heart  belong  maintained  by  artificial  circulation, 
but  many  hours  or  even  some  da3^s  after  somatic  death  pulsation 
may  be  restored  by  the  perfusion  of  such  a  solution  of  inorganic 
salts  as  Locke's  through  the  coronary  vessels.  Kuliabko  in  this 
way  was  able  to  restore  a  rabbit's  heart  which  had  been  kept  forty- 
four  hours  in  the  ice-chest.  Even  after  an  interval  of  three  to  five 
days  from  the  death  of  the  animal,  in  other  experiments,  pulsation 
returned  in  certain  parts  of  the  heart,  while  twenty  hours  after 
death  from  double  pneumonia  the  heart  of  a  boy  three  months 
old  was  restored,  and  went  on  beating  for  over  an  hour.  He  obtained 
also  more  or  less  complete  restoration  of  the  beat  in  the  hearts  of 
persons  dead  from  bronchitis  combined  with  peritonitis  or  menin- 
gitis, and  from  cholera  infantum,  but  was  unsuccessful  in  cases  of 
diphtheria  compHcated  with  septicaemia  or  erysipelas,  and  in  cases 


154  TtiE  CIRCULATION  OP  THE  BLOOD  AND  LYMPH 

of  pleurisy  with  effusion.  It  is  to  be  remarked,  however,  that 
although  beats  of  a  kind  can  be  obtained  a  long  time  after  death, 
they  are  either  confined  to  the  auricles  or  to  portions  of  them,  or, 
if  they  involve  the  ventricles  too,  they  are  only  shallow  and  local 
contractions,  especially  seen  in  the  neighbourhood  of  the  larger 
coronary  vessels,  and  are  utterly  inadequate  to  the  maintenance 
of  an  efficient  circulation.  The  heart  can  also  be  resuscitated  m  situ 
for  some  time  after  complete  stoppage  without  the  injection  of  any 
solution  by  clamping  the  aorta  in  the  thorax  and  practising  direct 
cardiac  massage,  the  lower  end  of  the  animal  at  the  same  time  being 
elevated  to  allow  blood  to  pass  out  of  the  engorged  abdominal  veins 
to  the  right  auricle.  The  clamping  of  the  aorta  permits  a  sufficient 
pressure  to  be  attained  for  the  filhng  of  the  coronary  arteries.  The 
injection  of  adrenalin  into  the  blood  has  also  been  recommended  as 
a  means  of  raising  the  blood-pressure  by  constricting  the  small 
arteries,  and  stimulating  the  action  of  the  cardiac  muscle.  The 
possibility  of  restoration  of  the  mammalian  heart  many  hours  after 
somatic  death  has  been  considered  by  some  a  strong  argument  for 
the  myogenic  theory  of  cardiac  automatism,  since,  they  say,  it  is 
improbable  that  ganglion-cells,  elsewhere  such  physiologically 
fragile  structures,  should  in  the  heart  retain  their  vitality  for  so 
long  a  time.  But  it  is  easy  to  overdo  this  argument,  and  we  must 
not  assume  without  proof  that  ganghon-cells  in  all  parts  of  the  body 
have  an  equal  capacity  of  survival.  Indeed,  we  know  that  there 
are  great  differences,  the  nervous  mechanism  concerned  in  respira- 
tion, e.g.,  being  capable  of  restoration  when  the  circulation  is  re- 
newed after  total  anaemia  of  the  brain  and  cervical  cord  lasting  for 
as  much  as  an  hour  (in  cats),  while  the  nervous  mechanism  con- 
cerned in  voluntary  movements  cannot  be  completely  restored  even 
after  a  much  shorter  interval.  It  is  very  probable  that  the  cardiac 
ganglia,  if  the  all-important  automatic  function  of  the  heart  depends 
upon  them,  are,  Hke  the  cardiac  muscle,  endowed  with  exceptional 
powers  of  resistance  to  those  changes  which  constitute  death. 
The  possibility  also  must  not  be  overlooked  that  the  contractions 
obtained  after  such  long  intervals  are  not  truly  automatic,  but 
similar  rather  to  the  rhythmical  beats  developed  under  the  influence 
of  pressure  in  the  frog's  apex  preparation  or  by  immersion  in  salt 
solutions  of  tortoise  ventricle  strips. 

In  addition  to  its  marked  power  of  rhythmical  contraction,  the 
cardiac  muscle  is  distinguished  from  ordinary  skeletal  muscle  by 
other  peculiarities.  It  used  to  be  considered  the  most  striking  of 
these  peculiarities  that  '  it  is  everything  or  nothing  with  the  heart  '; 
in  other  words,  that  the  heart  muscle,  when  it  contracts,  makes  the 
best  effort  of  which  it  is  capable  at  the  time;  a  weak  stimulus,  if 
it  can  just  produce  a  beat,  causing  as  great  a  contraction  as  a  strong 
stimulus.     Recent  work,  however,  has  indicated  that  this  property 


fHB  tiEART-BEAt  ih!  ITS  PHYSIOLOGICAL  RELATlOi\S      155 

is  also  possessed  by  the  skeletal  muscle- fibre.  When  a  whole  skeletal 
muscle  is  excited  either  directly  or  through  its  motor  nerve,  it  is 
true  that  throughout  a  considerable  range  increase  of  stimulus  is 
accompanied  by  an  apparent  increase  in  the  strength  of  contraction. 
But  there  is  reason  to  believe  that  this  is  because  a  larger  and  larger 
number  of  fibres  become  involved  in  the  excitation  as  the  stimulus 
is  increased,  and  not  because  each  fibre  responds  more  and  more 
strongly  (Lucas).  In  skeletal  muscle  the  fibres  are  completely 
isolated  from  each  other,  and  the  excitation  does  not  spread  from 
fibre  to  fibre,  as  happens  in  the  heart. 

Refractory  Period  and  Extra  Contraction  of  Hean  Muscle. — A 
more  characteristic  property  of  the  cardiac  muscle  tha  1  the  '  all  or 
nothing  '  law  is  that  a  true  tetanus  of  the  heart  cannor  be  obtained 
at  all,  or  only  under  very  special  conditions.  When  the  ventricle 
of  a  normally  beating  frog's  heart  is  stimulated  by  a  rapid  series  of 
induction  shocks,  its  rate  is  generally  increased,  but  there  is  no 
definite  relation  between  the  number  of  stimuli  and  the  number  of 
beats.  Many  of  the  stimuH  are  ineffective.  In  the  same  way  a 
portion  of  the  heart,  such  as  the  apex  of  the  ventricle,  when  stimu- 
lated in  the  quiescent  condition  by  an  interrupted  current,  responds 
by  a  rhythmical  series  of  beats,  and  not  by  a  tetanus.  It  is  evident 
that  the  cardiac  muscle,  like  ordinary  striped  muscle,  is  for  some 
time  after  excitation  incapable  of  responding  to  a  fresh  stimulus — 
i.e.,  there  is  a  refractory  period.  But  this  is  immensely  longer  in 
cardiac  than  in  skeletal  muscle.  When  the  phenomenon  is  analyzed, 
it  is  found  that  a  stimulus  falling  into  the  heart  muscle  between  the 
moment  at  which  the  contraction  begins  and  the  moment  at  which 
it  reaches  its  maximum  produces  no  effect — is,  so  to  speak,  ignored. 
When  the  stimulus  is  thrown  in  at  any  point  between  the  maximum 
of  the  systole  and  the  beginning  of  the  next  contraction,  it  causes 
what  is  called  an  extra  contraction.  The  extra  contraction  is 
followed  by  a  longer  pause  than  usual — a  so-called  compensatory 
pause — which  just  restores  the  rhythm,  so  that  the  succeeding 
systole  falls  in  the  ciurve  where  it  would  have  fallen  had  there  been 
no  extra  contraction  (Fig.  68). 

In  man,  extra  systoles  followed  by  compensatory  pauses  may  occur 
under  pathological  conditions,  giving  rise  to  an  important  group  of 
cardiac  irregularities.  Tlicsc  extra  systoles  may  be  cither  auricular  or 
ventricular,  the  auricle  or  the  ventricle  contracting  prematurely  without 
waiting  for  the  signal  of  the  sinus  rhythm.  The  analysis  of  pulse- 
tracings  showing  these  irregularities  has  led  to  results  of  great  physio- 
logical and  clinical  interest  (Cushny,  Mackenzie,  etc.),  but  cannot  be 
dwelt  on  here.  When  every  second  beat  is  an  extra  systole,  generally 
weaker  than  the  preceding  and  the  succeeding  normal  beat,  the  condi- 
tion is  called  pulsus  bigeminus-  The  weaker  beat  is  always  followed 
by  a  compensatory  pause  of  greater  duration  than  that  preceding  it. 
From  the  pulsus  bigeminus  must  be  distinguished  that  form  of  alterna- 
ting pulse  termed  pulsus  alternans,  in  which  every  second  beat  is  dimin- 
shed  in  size,  but  the  intervals  separating  the  beats  are  of  uniform  length. 


156 


The  circulation  of  the  blood  and  lyMPU 


The  refractory  period  is  shorter  for  strong  than  for  weak  stimuli, 
and  is  markedly  diminished  by  raising  the  temperature  of  the  heart. 
So  that  stimulation  of  the  heated  heart  with  a  series  of  strong 
induction  shocks  may  cause  a  tetaniform  condition,  if  not  a  typical 

tetanus.  The  con- 
traction of  the 
normally  beating 
heart  is  really  a 
simple  contrac- 
tion, and  not  a 
tetanus.  The 
electrical  changes 
correspond  to  a 
single  contraction 
(p.  806);  and  when 
the  nerve  of  a 
nerve-muscle  pre- 
paration is  laid 
on  the  heart,  the 
muscle  responds 
to  each  beat  by  a 
simple  twitch, 
and  not  by  tet- 
anus (p.  201). 
That  the  cardiac 
muscle  itself,  apart  from  the  intrinsic  nervous  mechanism,  shows 
the  phenomenon  of  '  refractory  state  '  has  been  shown  in  the 
Limulus  heart  after  extirpation  of  the  ganglion  (Carlson). 

Like  ordinary  skeletal  muscle,  the  cardiac  muscle  is  at  first  bene- 
fited by  contraction,  perhaps  by  an  '  augmenting  '  action  of  fatigue- 
products  such  as  carbon  dioxide  (Lee),  so  that  when  the  apex  is 
stimulated  at  regular  intervals  each  contraction  is  somewhat 
stronger  than  the  preceding  one.  To  this  phenomenon  the  name  of 
the  staircase  or  '  treppe  '  has  been  given,  from  the  appearance  of  the 
tracings  (p.  723). 


Fig.  68.  —  Refractory  Period  and  Compensatory  Pause 
(Marey).  A  frog's  heart  was  stimulated  at  a  point  corre- 
sponding to  the  nick  in  the  horizontal  line  below  each 
curve.  In  i  and  2  there  was  no  response ;  in  3  and  4  there 
was  an  extra  contraction,  succeeded  by  a  compensatory 
pause. 


Section  V. — ^The  Nervous  Regulation  of  the  Heart 
(Extrinsic  Nervous  Mechanism  of  the  Heart). 

While,  as  we  have  seen,  the  essential  cause  of  the  rhythmical  beat 
of  the  heart  resides  in  the  tissue  of  the  heart  itself,  it  is  constantly 
affected  by  impulses  that  reach  it  from  the  central  nervous  system. 
These  impulses  are  of  two  kinds,  or,  rather,  produce  two  distinct 
effects:  inhibition,  shown  by  a  diminution  in  the  rate  or  force  of  the 
heart-beat,  or  in  the  ease  with  which  the  contraction  is  conducted 
over  the  heart-wall;  and  augmentation,  or  increase  in  the  rate  or 


THE  NERVOUS  REGULATION  OF  THE  HEART 


157 


force  of  the  beat  or  in  the  conductivity.  Both  the  inhibitory  and 
th-  augmentor  impulses  arise  in  the  medulla  oblongata,  and  perhaps 
a  narrow  zone  of  the  neighbouring  portion  of  the  cord;  and  they  can 
be  artificially  excited  by  stimulation  in  this  region.  They  pursue 
their  course  to  the  heart  by  fibres  which  may  in  certain  animals  be 
mingled  together,  but  are  anatomically  distinct.  We  may,  there- 
fore, divide  the  extrinsic  or  external  nervous  mechanisrr  of  the 
heart  into  a  cardio-inhibitory  centre  with  its  efferent  inhibitory 
nerve- fibres  and  a  cardio-augmentor  centre  with  its  efferent  acceler- 
ator or  augmentor  fibres.  Both  of  those  centres,  as  we  shall  see, 
have,  in  addition,  extensive  relations 
with  afferent  nerve-fibres  from  all  parts 
of  the  body,  including  the  heart  itself. 

It  was  in  the  vagus  of  the  frog  that 
inhibitory  nerves  were  first  discovered 
by  the  brothers  Weber  seventy  years 
ago,  and  even  now  our  knowledge  of  the 
cardiac  nervous  mechanism  is  more  com- 
plete in  this  animal  than  in  any  other. 
We  shall,  therefore,  first  describe  the 
phenomena  of  inhibition  and  augmen- 
tation as  we  see  them  in  the  heart  of  the 
frog,  and  then  pass  on  to  the  mammal. 

In  the  frog  the  inhibitory  fibres  leave 
the  medulla  oblongata  in  the  vagus  nerve. 
The  augmentor  fibres  come  ofi  from  the 
upper  part  of  the  spinal  cord  by  a  branch 
from  the  third  nerve  to  the  third  sympa- 
thetic ganglion,  and  thence  find  their  way 
along  the  sympathetic  cord  to  its  junction 
with  the  vagus,  in  which  they  run,  mingled 
with  the  inliibitory  fibres,  down  to  the  heart. 

When  the  vago-sympathetic  in  the 
frog  or  toad  is  cut,  and  its  peripheral 
end  stimulated,  the  heart  in  the  vast 
majority  of  cases  is  stopped  or  slowed, 
or  its  beat  is  distinctly  weakened  without,  it  may  be,  any  marked 
slowing.  In  other  words,  the  rate  at  which  the  heart  was 
working  before  the  stimulation  is  greatly  diminished,  or  reduced 
to  zero.  Such  an  effect,  a  diminution  of  the  rate  of  working, 
we  call  Inhihition.  What  precise  form  the  inhibition  shall  take, 
whether  the  stoppage  shall  be  complete  or  partial,  and  if  partial 
whether  the  beats  shall  be  simply  weakened  without  being  slowed 
or  both  slowed  and  weakened,  appears  to  depend  partly  upon  the 
strength  of  the  stimulus  used  and  partly  upon  the  state  of  the 
heart  itself.  Some  hearts  it  may  be  impossible  to  stop  with  weak 
stimulation,  although  other  signs  of  inhibition  may  be  distinct; 


Fig.  69. — Diagram  of  Extrinsic- 
Nerves  of  Frog's  Heart  (after 
Foster).  Ill,  3rd  spinal 
nerve;  AV,  annulus  of  Vieus- 
sens;  X,  roots  of  vagus;  IX, 
glosso-pharyngeal  nerve;  V'S, 
combined  vagus  and  svinpa- 
thetic;  i,  2,  and  3,  the  ist, 
2nd.  and  3rd  sympathetic 
ganglia.  The  dcirk  line  indi- 
cates the  course  of  the  sym- 
pathetic fibres.  The  arrows 
show  the  direction  of  the  aug- 
mentor impulses. 


158  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

while  they  are  readily  stopped  by  stronger  stimulation.  In  other 
cases  the  strongest  stimulation  may  not  produce  complete  standstill. 
Again,  the  inhibitory  effect  produced  on  a  heated  heart  by  a  given 
strength  of  stimulation  of  the  vagus  may  be  greater  than  that  caused 
in  a  heart  at  the  ordinary  temperature  or  a  cooled  heart.  This  is 
especially  evident  on  the  auricular  tracings  when  these  are  recorded 
separately  from  those  of  the  ventricle.  Even  on  the  verge  of  heat 
standstill  of  the  heart  inhibition  is  easity  obtained  (Fig  71).  Some 
writers  have  assumed  that  the  different  inhibitory  effects  produced 
by  the  vagus  are  due  to  the  existence  in  it  of  separate  groups  of  fibres, 
some  affecting  only  the  rate  of  the  contraction,  others  its  strength. 


Fig.  70. — Tracing  Ir^^iu  i  rog  &  Heart.  A,  auiicular,  V,  ventricular  tracing.  Sinus 
stimulated  (primary  coil  70  mm.  from  secondary).  Heart  at  temperature 
11-2°  C.  Complete  standstill.  The  time-tracing  between  the  curves  marks 
intervals  of  two  seconds. 

others  still  the  conductivity  of  the  muscular  tissue  and  its  excita- 
bility. This  theory  has  enriched  the  vocabulary  of  physiology 
with  a  number  of  sonorous  terms  derived  from  the  Greek,  but  has 
not  otherwise  established  itself,  although  it  has  been  useful  in 
emphasizing  the  fact  that  the  inhibitory  nerves  can  influence  the 
heart-beat  in  several  distinct  ways. 

But  there  are  other  points  of  importance  to  be  noted  in  regard  to 
this  inhibition :  (i)  It  does  not  begin  for  a  Httle  time  after  stimulation 
has  begun.  In  other  words,  there  is  a  distinct  latent  period;  and 
the  length  of  this  latent  period  is  related  to  the  phase  of  the  heart's 


THE  NERVOUS  REGULATION  OF  THE  HEART 


159 


contraction  at  which  the  stimulus  is  thrown  in,  and  to  the  rate  at 
which  the  heart  is  beating.  As  a  general  rule,  the  heart  makes  at 
least  one  beat  before  it  stops. 

(2)  The  inhibition  does  not  continue  indefinitely,  even  if  stimula- 
tion of  the  nerve  is  kept  up.  Sooner  or  later,  and  usually,  in  fact, 
after  an  interval  of  a  few  seconds,  the  heart  begins  again  to  beat  if  it 
has  been  completely  stopped,  or  to  quicken  its  beat  if  it  has  only  been 
slowed,  or  to  strengthen  it  if  the  inhibition  has  only  weakened  the 
contraction,  and  it  soon  regains  its  old  rate  of  working.  Not  only 
so,  but  very  often  there  follows  a  longer  or  shorter  period  during 
which  the  heart  works  at  a  greater  rate  than  it  did  before  the  inhibi- 
tion, and  this  greater  rate  of  working  may  be  manifested  by  increased 


AuT. 


Verit. 


Fig.  71. — .Activity  of  Vagus  on  Verge  of  Heat  Standstill.  Auricular  and  ventricular 
contractions  of  toad's  heart  recorded.  Heart  at  34*5''  C,  v  50,  stimulation  of 
vagus  (distance  of  coils  50  mm.).  The  ventricle  was  already  in  heat  standstill; 
the  auricle  was  at  once  inhibited.  Then  follows  secondary  augmentation  (due 
to  the  sympathetic  fibres),  during  which  the  ventricle  also  resumes  beating. 
An  interval  of  a  minute  elapsed  between  the  first  and  second  parts  of  the 
tracing,  during  which  the  heart  remained  at  34'5''  C.  The  auricle  was  almost 
in  standstill  (contractions  can  still  be  seen  on  the  curve  with  a  lens),  when  the 
vagus  was  again  stimulated  at  v  50  with  the  same  distance  between  the  coils. 
Complete  inhibition  followed  by  secondary  augmentation. 

frequency  of  beat,  or  increased  strength  of  beat,  or  by  both.  When 
the  temperature  of  the  heart  is  low,  increased  frequency ;  when  it  is 
high,  increased  strength,  is  generally  seen  during  this  period  of 
secondary  augmentation.*  The  cause  of  this  secondary  augmentation, 
and  of  the  primary  augmentation  sometimes  seen  in  fresh  prepara- 
tions and  often  in  hearts  that  have  been  long  exposed  (Fig.  73), 
excited  much  speculation  before  it  was  known  that  sympathetic 
fibres  existed  in  the  vagus.  There  is  no  longer  any  doubt  that  it  is 
due  to  the  stimulation  of  these  accelerator  or,  as  it  is  better  to  call 

*  Augmentation  is  termed  '  secondary  '  when  it  is  preceded  by  inhibition, 
'  primary  '  when  it  is  not  so  preceded. 


i6o  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

them  (since  mere  acceleration  is  not  the  only  consequence  of  their 
stimulation),  augmentor  fibres  in  the  mixed  nerve.  For  (i)  excita- 
tion of  the  roots  of  the  vagus  proper  within  the  skull,  and  therefore 
above  the  junction  of  the  sympathetic  fibres,  causes  no  secondary 
augmentation,  or  very  little,  and  the  inhibition  lasts  far  longer  than 
when  the  mixed  trunk  is  stimulated.  (2)  Excitation  of  the  upper 
or  cephaHc  end  of  the  sympathetic  cord  before  it  has  joined  the 
vagus  causes,  after  a  relatively  long  latent  period,  marked  augmenta- 
tion. And  if  the  contractions  of  the  heart  are  registered,  the 
tracing  bears  a  close  resemblance  to  the  curve  of  secondary  augmen- 
tation following  excitation  of  the  mixed  nerve  on  the  other  side 
with  an  equally  strong  stimulus  and  for  an  equal  time.  (3)  When 
the  vago-sympathetic  is  stimulated  weakly  there  is  little  or  no 


Fig.  72. — Frog's  Heart:  Vagus  stimulated.  Temperature  of  heart  8°  C;  78  mm. 
between  the  coils.  Diminution  in  force  of  auricle  and  ventricle,  but  not  com 
plate  standstill.     Time-tracing  shows  two-second  intervals. 

secondary  augmentation.  Now,  it  is  known  that  the  augmentor 
fibres  require  a  comparatively  strong  stimulus  to  cause  any  effect 
when  they  are  separately  excited,  whereas  a  weak  stimulus  will 
excite  the  inhibitory  fibres. 

The  question  arises  at  this  point,  why  it  is  that,  when  the  inhibitory 
and  augmentor  fibres  are  stimulated  together  in  the  mixed  nerve  (and 
the  same  is  true  when  the  sympathetic  on  one  side  and  the  vagus  on 
the  other  are  stimulated  at  the  same  time),  the  inhibitory  effect  always 
comes  first,  when  there  is  any  inhibitory  effect,  while  the  augmentation 
.always  has  to  follow.  The  answer  has  sometimes  been  given,  that  the 
latent  period  of  the  augmentor  fibres  is  longer  than  that  of  the  inhibitory 
fibres.  But  although  this  is  certainly  the  case,  the  answer  is  insuffi- 
cient.    For  the  period  of  postponement  may  be  much  greater  than  the 


THE  NERVOUS  REGULATION  OF  THE  HEART  l6i 

latent  period  of  the  sympathetic  fibres  when  stimulated  by  themselves. 
The  inhibition  apparently  runs  its  course  without  being  affected  by  the 
simultaneous  augmentor  effect,  which,  lying  latent  until  the  end  of  the 
inhibition,  then  bursts  out  and  completes  its  own  curve.  It  is  not  like 
the  passing  of  two  waves  through  each  other,  but  rather  like  the  stopping 
of  one  wave  until  the  other  has  passed  by.  It  seems  as  if  augmentation 
cannot  develop  itself  in  the  presence  of  inhibition — at  least,  until  the 
latter  is  nearly  spent.  Like  a  musical-box  devised  to  play  a  series  of 
melodies  in  a  fixed  order,  and  from  which  a  particular  tune  cannot  be 
obtained  till  those  preceding  it  have  been  run  through,  the  heart,  in 
some  way  or  other,  is  arranged,  in  the  presence  of  competing  impulses 
from  its  extrinsic  nerves,  to  play  the  tunc  of  inhibition  before  the  tune 


Fig-  73- — Frog's  Heart.  A,  auricular.  V,  ventricular  tracing.  Ventricle  beating  very 
feebly.  Vagus  stimulated  (60  nun.  between  coils).  Marked  augmentation  of 
ventricular  beat. 

of  augmentation.  In  the  frog,  at  any  rate,  the  two  processes  can  hardly 
be  considered  as  antagonistic,  in  the  sense  that  a  definite  amount  of 
augmentor  excitation  can  overcome  a  definite  amount  of  inhibiton- 
excitation.  Nor  is  it  the  case  that,  when  the  heart  is  played  upon  at 
the  same  time  by  impulses  of  both  kinds,  it  pits  them  against  each  other 
and  strikes  the  balance  accurately  between  them.  It  is  possible,  how- 
ever, that  when  the  inhibitory  fibres  are  very  weakly,  and  the  augmentor 
fibres  very  strongly  stimulated,  the  amount  of  inhibition  may  be  some- 
what diminished.  In  mammals,  on  the  other  hand,  a  true  antagonism 
seems  to  exist;  and  stimulation  of  the  inhibitor^'  nerves  is  less  effccti\e 
when  the  augmcntors  are  excited  at  the  same  time.  The  cardiac  nerves 
affect  not  only  the  rate  and  force  of  the  contraction,  but  also  the  con- 

i: 


1 62 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


ductivity  of  the  heart.  Thus  in  the  frog's  heart  during  stimulation  of 
the  vagus,  the  contraction  passes  more  slowly,  and  during  stimulation 
of  the  sympathetic  more  quickly,  from  auricles  to  ventricle. 

In  mammals  (and  in  what  follows  we  shall  restrict  ourselves  chiefly 
to  the  dog,  cat,  and  rabbit,  as  it  is  in  these  animals  that  the  subject 
has  been  most  carefully  studied)  the  inhibitory  fibres  run  down  the 
vagus  in  the  neck  and  reach  the  heart  by  its  cardiac  branches.  They 
are  derived  from  the  bulbar  roots  of  the  spinal  accessory,  whose  inner 
branch  joins  the  vagus.  The  aitgmentor  fibres  leave  the  spinal  cord  in 
the  anterior  roots  of  the  second  and  third  thoracic  nerves,  and  possibly 

to  some  extent  by  the  fourth  and  fifth. 
Through  the  corresponding  white  rami 
communicantes  they  reach  the  sympa- 
thetic cord,  and  running  up  through  the 
stellate  ganglion  (first  thoracic),  and  the 
annulus  of  Vieussens,  which  surrounds 
the  subclavian  artery,  to  the  inferior 
cervical  ganglion,  they  pass  off  to  the 
heart  by  separate  '  accelerator '  branches, 
taking  origin  either  from  the  annulus  or 
from  the  inferior  cervical  ganglion.  Some 
augmentor  fibres  are  often,  if  not  always, 
present  in  the  dog's  vago-sympathetic  in 
the  neck.  It  is  especially  easy  to  demon- 
strate their  presence  five  or  six  days  after 
section  of  the  nerve,  when  the  excitability 
of  the  inhibitory  fibres  has  disappeared. 
In  the  dog  the  vagus  and  cervical  sym- 
pathetic are,  in  the  great  majority  of 
cases,  contained  in  a  strong  common 
sheath,  and  pass  together  through  the 
inferior  cervical  ganglion.  Upon  opening 
this  sheath  they  may  with  care  be  separ- 
ated, the  fibres  running  in  distinct  strands, 
and  not  mixed  together  as  in  the  vago- 
sympathetic of  the  frog.  For  some  dis- 
tance; below  the  superior  cervical  ganglion 
the  cervical  sympathetic  is  not  connected 
with  the  vagus,  and  here  the  nerves  may 
be  separately  stimulated  without  any 
artificial  isolation.  In  the  rabbit  and  some 
other  mammals,  including  man,  the  vagus 
and  sympathetic  run  a  separate  course  in 
the  neck. 


Fig.  74. — Diagram  of  Cardiac 
Nerves  in  the  Dog  (after 
Foster).  II,  III,  second  and 
third  dorsal  nerves;  SA,  sub- 
clavian artery;  AV,  annulus  of 
Vieussens;  ICG,  inferior  cer- 
vical ganglion;  CS,  cervical 
sympathetic;  i,  first  thoracic 
or  stellate  ganglion  of  the 
sympathetic;  2,  second  thora- 
cic ganglion;  Ac,  accelerator 
or  augmentor  fibres  passing 
off  towards  the  heart;  X,  roots 
of  vagus;  XI,  roots  of  spinal 
accessory;  JG,  jugular  gan- 
glion; GTV,  ganglion  trunci 
vagi;  In.,  inhibitory  fibi'es 
passing  off  towards  the  heart. 


The  effects  of  stimulation  of  the 
vagus  or  vago  -  sympathetic  in  the 
mammal  are  very  much  the  same 
as  in  the  frog,  except  that  secon- 
dary augmentation  is  in  general  less  marked,  though  often  present 
in  some  degree,  and  that  in  the  mammal  the  inhibitory  fibres  have 
a  smaller  direct  action  on  the  ventricle.  It  indeed  beats  more 
slowly  when  the  auricle  is  slowed,  but  this  is  only  because  in  the 
normally  beating  heart  the  ventricle  takes  the  time  from  the 
auricle.     The  strength  of  the  ventricular  contractions  may  be  not  at 


THE  NERVOUS  REGULATION  OF  THE  HEART 


163 


all  diminished,  even  when  the  auricle  is  beating  very  feebly  during 
inhibition.  When  the  auricle  is  completely  stopped,  which  does 
not  occur  so  readily  as  in  the  frog,  the  ventricle  also  stops  for  a 
short  time,  but  soon  begins  to  beat  again  with  an  independent 
rhythm  of  its  own.  In  the  frog  the  ventricle  is  directly  affected 
by  stimulation  of  the  vagus,  and  the  force  of  its  beats  is  diminished 
independently  of  the  inhibitory  effect'^  in  the  auricles  (Practical 
Exercises,  pp.  196,  201). 

The  inhibitory  fibres,  then,  influence  the  heart  particularly 
through  the  auricles;  they  are  par  excellence  auricular  nerves.  On 
the  other  hand,  the  accelerantes  in  all  mammals  which  have  been 
investigated  not  only  extend  to  the  ventricles,  but  are  even  mainly 
distributed  to  them. 
They  are  emphatically 
ventricular  fibres,  and 
in  accordance  with  its 
greater  mass  the  left 
ventricle  receives  more 
fibres  than  the  right. 

Stimulation  of  the 
accelerator  nerves  in 
the  dog  causes  an  in- 
crease in  the  force  of 
both  the  auricular  and 
ventricular  contraction, 
and  as  a  rule,  in  addi- 
tion, some  increase  in 
the  rate  of  the  beat. 

As  to  the  nature  of 
the  physiological  link- 
age between  the  cardiac 
nerves  and  the  mus- 
cular tissue  of  the  heart 
we  know  but  little. 
Ganglion-cells  he  on  the  course  of  the  vagus  fibres  after  they  have 
entered  the  heart,  and  although  the  view  has  been  advocated  that 
they  are  simply  stations  where  the  inhibitory  impulses  pass  from 
meduUated  to  non-medullated  fibres,  and  where  possibly  other 
anatomical  changes  and  rearrangements  occur,  they  may  be  inter- 
mediate mechanisms  which  essentially  modify  the  physiological 
impulses  falling  into  them.  It  has  been  stated  that  in  the  dog  the 
right  vagus  controls  chiefly  the  rate  of  the  heart,  and  the  left  vagus 
chiefly  the  conduction  from  auricles  to  ventricles,  and  the  suggestion 
has  been  made  that  this  is  because  the  right  vagus  has  a  special 
relation  to  the  sino-auricular  node,  in  which  impulses  are  supposed 
to  arise,  and  the  left  vagus  a  special  relation  to  the  auriculo-ven- 


Fig.  75. — Blood- Pressure  Tracings:  Rabbit.  Vagus 
stimulated  at  i.  Stimulus  stronger  in  B  than  in 
A  (Hiirtfale's  spring  manometer). 


164  ^^^  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

tricular  node,  the  upper  end  of  the  A- V  bundle,  the  main  conduction 
system  (Cohn  and  Lewis). 

The  nervi  accelerantes  are  already  non-medullated  before  they 
reach  the  heart.  The  fact  that  the  action  of  the  accelerantes  can 
be  restored  by  perfusing  the  heart  with  a  nutrient  solution  at  a 
much  longer  interval  after  somatic  death  than  the  action  of  the 
vagus  strengthens  the  suggestion  that  ganglion-cells  are  interposed 
on  the  inhibitory  though  not  on  the  augmentor  path,  without, 
however,  proving  of  itself  that  such  a  difference  exists.  In  one 
experiment  the  heart  of  an  anthropoid  ape  was  revived  when  three 
successive  periods — viz.,  four  and  a  half,  twenty-eight  and  a  half, 
and  fifty-three  hours  respectively — had  elapsed  after  the  death  of 
the  animal,  although  during  the  last  period  the  heart  had  been 
twice  frozen  hard.  The  vagus  was  shown  to  be  still  capable  of 
causing  some  inhibition  six  hours  after  death,  and  the  accelerans 
some  augmentation  as  late  as  fifty-three  hours  after  death  (Hering). 

In  the  discussions  that  have  arisen  over  the  relation  of  the  extrinsic 
to  the  intrinsic  cardiac  nervous  apparatus  appeal  has  frequently  been 
made  to  the  action  of  certain  poisons  on  the  heart. 

Thus,  after  nicotine  has  been  injected  subcutaneously,  or  painted 
directly  on  the  heart  of  a  frog,  stimulation  of  the  vago-sympathetic 
causes  no  inhibition;  it  may  cause  augmentation.  But  stimulation  of 
the  junction  of  the  sinus  and  auricle  still  causes  inhibition,  as  in  the 
normal  heart. 

Atropine  and  its  allies,  such  as  daturine,  not  only  abolish  the  inhibi- 
tory effect  of  stimulation  of  the  vagus  trunk,  but  also  that  of  stimula- 
tion of  the  junction  of  sinus  and  auricle. 

Muscarine ,  a  poison  contained  in  certain  mushrooms  (p.  197),  causes 
diastolic  arrest  of  the  heart,  which,  when  the  circulation  is  intact,  be- 
comes swollen  and  engorged  with  blood.  This  action  takes  place  in  a 
heart  already  poisoned  with  nicotine  or  one  of  its  congeners,  but  not  in 
a  heart  under  the  influence  of  atropine  or  its  allies.  And  a  heart  brought 
to  a  standstill  by  muscarine  can  be  made  to  beat  again  by  the  applica- 
tion of  atropine,  although  not  by  nicotine. 

These  facts  may  be  explained  as  follows:  Nicotine  paralyzes,  not  the 
very  ends  of  the  vagus,  but  the  ganglia  through  which  its  fibres  pass. 
Stimulation  of  the  sinus,  which  is  practically  stimulation  of  the  vagus 
fibres  between  the  ganglion-cells  and  the  muscular  fibres,  is  therefore 
effective,  although  stimulation  of  the  nerve-trunk  is  not  (Langley). 
On  the  other  hand,  the  atropine  group  paralyzes  the  nerve-endings 
themselves,  or  interferes  with  the  reception  of  the  inhibitory  impulses 
by  acting  on  a  so-called  receptive  substance  in  the  muscle  (p.  180),  so 
that  neither  stimulation  of  the  sinus  nor  of  the  nerve-trunk  can  cause 
inhibition.  Muscarine,  on  the  contrary,  stimulates  the  vagus  fibres 
between  the  nerve-cells  and  the  muscle,  or  the  actual  nerve-endings,  or 
exerts  an  inhibitory  action  on  the  muscle  itself  through  the  appropriate 
receptive  substance,  and  thus  keeps  the  heart  in  a  state  of  permanent 
inhibition,  which  is  removed  when  atropine  cuts  out  the  nerve-endings, 
or  combines  with  the  receptive  substance.  It  is  quite  in  accordance 
with  this  that  muscarine  has  no  effect  on  a  heart  whose  vagus  nerves, 
as  occasionally  happens,  have  no  inhibitory  power.  Pilocarpine  has 
very  much  the  same  action  as  muscarine. 

The  view  that  muscarine  and  atropine  can  directly  affect  the  cardiac 


THE  NERVOUS  REGULATION  OF  THE  HEART 


165 


muscle  gains  a  certain  amount  of  support  from  the  facts  that  these 
drugs  act  very  much  in  the  same  way  on  the  heart  of  the  mammalian 
embryo  (rat,  rabbit,  etc.)  before  and  after  the  development  of  its  in- 
trinsic nervous  system,  and  that  the  passage  of  an  interrupted  current 
through  the  heart  of  very  young  embryos  causes  distinct  inhibition. 
But,  as  has  already  been  pointed  out,  it  is  not  legitimate  to  transfer 
without  question  to  the  muscle  of  the  fully  developed  heart  the  proper- 
ties of  the  embr^'onic  cardiac  tissue.  And,  on  the  other  hand,  musca- 
rine fails  to  affect  the  heart  in  many  invertebrate  animals — for  instance, 
in  Daphnia  (Pickering).  Yet  it  is  probable  that,  while  the  various 
tissues  in  the  heart  possess  a  different  susceptibility  to  one  and  the 
same  drug,  if  the  dose  is  large  enough  it  may  affect  them  all.  In  the 
Limulus  heart,  where  the  question  can  be  most  easily  tested,  it  has  been 
found  that  the  selective  action  of  alkaloids,  anaesthetics,  and  various 
other  substances  on  the 
three  heart -tissues  (gang- 
lion, motor  nerve  plexus, 
and  muscle)  is  one  of 
degree  only  (Meek). 

Stannius'  Experiment.— 
Another  scries  of  pheno- 
mena, intimately  related 
to  our  present  subject, 
have  excited,  since  they 
were  first  made  known  by 
Stannius,  an  enormous 
amount  of  discussion.  The 
chief  facts  of  this  classical 
experiment  we  have  al- 
ready mentioned  (p.  144), 
and  they  are  also  described 
in  the  Practical  Exercises 
(p.  192).  They  arc  easy 
to  verify,  but  difficult  to 
interpret.  The  most  prob- 
able explanation  of  the 
standstill  caused  by  the 
first  ligature  is  that  the 
lower  portion  of  the  heart, 
when  cut  off  from  the 
sinus  in  which  the  beat  normally  originates,  needs  some  time  for  the 
development  of  its  automatic  power  to  the  point  at  which  an  indepen- 
dent rhjrthm  can  be  maintained.  The  effects  following  the  second 
Stannius  ligature  seem  to  depend  upon  the  power  of  the  ventricle  to 
develop  and  maintain  an  independent  rhythm,  but  the  contractions  are 
supposed  by  some  to  be  started  by  stimulation  of  the  muscular  tissue 
in  the  auriculo-\-entricular  groove  by  the  ligature. 

Nature  of  Inhibition  and  Augmentation. — So  far  we  have  been  dis- 
cussing the  phenomena  of  inhibition  and  augmentation  as  ultimate 
facts.  We  have  not  attempted  to  go  behind  them,  nor  to  ask  what  it 
is  that  really  happens  when  inhibitoiy  impulses  fall  into  a  heart,  which 
from  the  first  days  of  embryonic  life  has  gone  on  beating  with  a  regular 
rhythm,  and  in  the  space  of  a  second  or  two  bring  it  to  a  standstill. 
The  question  cannot  fail  to  press  itself  upon  the  mind  of  anyone  who 
has  ever  witnessed  this  most  beautiful  of  physiological  experiments; 
but  as  yet  there  is  no  answer  except  ingenious  speculations.  The  most 
plausible  of  these  is  the  tropliic  theory  of  Gaskell,  who  sees  in  the  vagus 


Fig.  yfi_ — Frog's  Heart.  Sympathetic  stimulated 
{30  mm.  between  the  coils).  Temperature  12°. 
Marked  increase  in  force.  Only  auricular  tracing 
reproduced.    Time-trace,  two-second  intervals. 


i66 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


'mm^^^^mm 


a  nerve  which  so  acts  upon  the  chemical  changes  going  on  in  the  heart 
as  to  give  them  a  trophic,  or  anabohc,  or  constructive  turn,  and  thus  to 
lessen  for  the  time  the  destructive  changes  underlying  the  muscular 
contraction.  The  augmentor  nerves,  on  the  other  hand,  are  supposed 
to  exert  a  katabolic  influence,  and  to  favour  these  destructive  changes. 
And  while,  according  to  Gaskell,  the  natural  consequence  of  inhibition 
is  a  stage  of  increased  efficiency  and  working  power  when  the  inhibition 
has  passed  away,  the  natural  complement  of  augmentation  is  a  tem- 
porary exhaustion.  But  it  must  be  remembered  that  this  distinction 
is  not  as  yet  based  upon  any  very  solid  foundation  of  actually  observed 
and  easily  interpreted  facts. 

Whatever  the  exact  mechanism  of  augmentation  may  be,  there  is 
no  basis  for  the  statement  that  the  cardio-augmentor  nerves  have 
an  action  on  the  heart  so  fundamentally  different  from  the  action  of 
motor  nerves  on  skeletal  muscle  that  they  cannot  originate  contractions 

, — _  in  a  heart  entirely  at 

jlj'i/^  rest.      Excitation  of 

the  cardio-augmentor 
nerves  can  cause  rhyth- 
mical contractions  in 
the  perfectly  quiescent 
heart  of  molluscs,  and 
a  sudden  and  prolonged 
outburst  of  beats  of 
great  force  in  the  frog's 
heart,  which  has  been 
brought  to  a  standstill 
by  cautiously  heating 
it  to  40°  to  43°  C. 
(Practical  Exercises, 
p.  192)  for  a  minute  or 
two,  or  to  a  consider- 
ably lower  tempera- 
ture, for  a  longer  time 
(Fig.  77).  A  similar 
effect  can  be  obtained 
on  the  quiescent  mam- 
malian heart  by  stimu- 
lation of  the  nervi 
accelerantes. 


28"  5 
S3G 


I  M  M  M  I  I  I  I  I  I   I  I  I  I  I  I  I  I  I  I  I  I   !  I  |-T1  I  I  I  I   I  I  I  I  I  I  I  ■ 


^'^.^'^^'VY^' 


Fig.  77. — Effect  of  Stimulation  of  Frog's  Cardiac  Sym- 
pathetic during  Complete  Standstill  of  the  Heart  at 
28-5°  C.  Upper  tracing,  auricle;  lower,  ventricle. 
To  be  read  from  right  to  left.  Time-trace,  two- 
second  intervals. 


The  Normal  Exci- 
tation of  the  Cardiac 
Nervous  Mechanism. 
— We  have  now  to  in- 
quire how  this  elaborate  nervous  mechanism  is  normally  set  into 
action.  And  we  may  say  at  once  that,  striking  as  are  the  effects 
of  experimental  stimulation  of  the  vagus  trunk  or  the  nervi 
accelerantes  in  their  course,  it  is  only  under  exceptional  cir- 
cumstances that  the  efferent  nerve-fibres,  at  any  rate  before  they 
have  entered  the  heart,  can  be  directly  excited  in  the  intact  body. 
In  certain  cases  the  pressure  of  a  tumour  or  an  aneurism  on  the 
nerve-trunks,  or,  in  the  case  of  the  accelerators,  the  progress  of  a 
pathological  change  in  the  sympathetic  ganglia  through  which  the 


THE  NERVOUS  REGULATION  OF  THE  HEART  167 

fibres  pass,  has  been  thought  to  bring  about  by  direct  stimulation 
a  slowing  or  a  quickening  of  the  pulse.  In  some  individuals  the 
vagus  has  been  excited  by  compressing  it  agaifist  a  bony  tumour 
in  the  neck;  and  by  compressing  the  nerve  against  the  vertebral 
column  it  is  possible  to  cause  inhibition  in  many  normal  persons, 
although  it  ought  to  be  stated  that  the  experiment  is  not  free  from 
danger.  But  it  is  from  the  cardio-inhibitory  and  cardio-augmcntor 
centres  in  the  medulla  oblongata  that  the  impulses  which  regulate 
the  activity  of  the  heart  are  normally  discharged.  Inhibitory  im- 
pulses are  constantly  passing  out  from  the  medulla,  for  section  of 
both  vagi  causes  almost  invariably  an  increase  in  the  rate  of  the 
heart,  at  least  in  mammals,  although  the  increase  is  less  conspicuous 
in  animals  like  the  rabbit,  whose  normal  pulse-rate  is  high,  than  in 
animals  like  the  dog,  whose  pulse-rate  is  comparatively  low.  Section 
of  one  vagus  usually  causes  only  a  comparatively  shght  increase,  for 
the  other  is  able  of  itself  to  control  the  heart.  It  is  not  certainly 
known  whether  the  augmentor  centre  in  like  manner  discharges  a 
continuous  stream  of  impulses,  or  is  only  roused  to  occasional  activity 
by  special  stimuli.  For  the  results  of  section  of  the  nervi  acceler- 
antes,  or  the  extirpation  of  the  inferior  cervical  and  stellate  gangUa, 
are  dubious  and  conflicting.  But  if  it  does  exert  a  tonic  influence 
on  the  heart,  this  is  feebler  than  the  tone  of  the  inhibitory  centre. 
As  to  the  nature  of  this  inhibitory  tone,  and  the  manner  in  which  it 
is  maintained,  we  know  but  little.  It  may  be  that  the  chemical 
changes  in  the  nerve-cells  of  the  inhibitory  centre  lead  of  themselves 
to  the  discharge  of  impulses  along  the  inhibitory  nerves.  But  there 
is  some  evidence  that,  in  the  complete  absence  of  stimulation  from 
without,  the  activity  of  the  centre  would  languish,  and  perhaps  be 
ultimately  extinguished.  For  when  the  greater  number  of  the 
afferent  impulses  have  been  cut  off  from  the  medulla  oblongata  by 
a  transverse  section  carried  through  its  lower  border,  division  of  the 
vagi  produces  little  effect  on  the  rate  of  the  heart.  Also,  when  the 
upper  cervical  cord  and  the  brain  are  resuscitated  after  a  period  of 
ansemia,  the  return  of  cardio-inhibitory  tone  is  tardy  in  comparison 
with  the  return  of  the  truly  automatic  function  of  respiration,  and 
does  not  seem  to  precede  the  opening  up  of  the  afferent  paths  to  the 
cardio-inhibitory  centre.  Indeed,  reflex  inhibition  may  be  produced 
at  a  time  when  the  inhibitory  centre  has  regained  none  of  its  tone. 
The  suggestion  is  that  the  normal  tone  of  the  centre  is  largely 
dependent  upon  reflex  impulses.  Be  this  as  it  ma^',  we  know  that 
the  activity  of  the  inhibitory  centre  is  profoundly  influenced — and 
that  both  in  the  direction  of  an  increase  and  of  a  diminution — by 
impulses  that  fall  into  it  through  afferent  nerves  and  by  stinuiU 
directly  applied  to  it.  And  we"  may  assume  that  the  same  is  true 
of  the  augmentor  centre.  The  common  statement  that  stimulation 
of  the  central  end  of  one  vagus,  the  other  being  intact,  produces 


i68  rH£  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

distinct  inhibition  does  not  hold  for  all  mammals.  In  dogs  this  is 
sometimes  the  case,  but  often  (under  anaesthesia,  at  any  rate)  there 
is  little  or  no  inhibition,  or  even  augmentation.  In  etherized  cats, 
on  the  other  hand,  some  inhibition  is  always  seen.  Of  all  the  afferent 
fibres  of  the  vagus,  the  pulmonary  fibres  produce  the  most  marke<3 
reflex  inhibition.     The  cardiac  fibres  are  much  less  effective. 

These  pulmonary  nerves  also  influence  the  respiratory  and  vaso- 
motor centres.  The  respiration  is  temporarily  arrested,  and  the 
blood-pressure  falls  through  the  dilatation  of  the  small  arteries  when 
they  are  excited.  It  is  of  interest  in  connection  with  the  subject 
of  death  during  the  administration  of  angesthetics,  that  the  afferent 
vagus  fibres  coming  from  the  alveoli  of  the  lungs  can  be  chemically 
stimulated  when  irritant  vapours,  such  as  chloroform,  hydrochloric 
acid,  ammonia,  bromine,  or  formaldehyde  are  inhaled  through  a 
tracheal  cannula,  causing  reflex  arrest  of  the  heart  and  of  the  respira- 
tory movements  and  a  fall  of  blood-pressure  through  vaso- dilatation 
(Brodie).  At  a  certain  stage  in  chloroform  anaesthesia,  before  it 
has  become  very  deep,  comparatively  trifling  causes  may  bring 
about  great  and  sudden  changes  in  the  pulse-rate,  owing  to  the 
abnormal  mobility  of  the  vagus  centre  (MacWilHam). 

The  depressor  nerve,  a  branch  of  the  vagus,  which  is  easily  found 
in  the  rabbit  as  a  slender  nerve  running  close  to  the  sympathetic 
in  the  neck,  and  a  Uttle  to  its  inner  side,  but  in  the  dog  is  usually 
blended  with  the  vago-sympathetic,  falls  into  the  same  category 
with  the  vagus  itself  as  regards  its  reflex  action  on  the  heart,  to 
which  it  bears  an  important  relation.  In  all  mammals  some  of  its 
fibres  end  in  the  wall  of  the  aorta,  but  some  of  them  may  run  down 
over  the  heart  to  the  ventricle.  Stimulation  of  its  peripheral  end 
has  no  effect,  for  the  fibres  in  it  which  influence  the  circulation  are 
afferent,  not  efferent.  But  excitation  of  its  central  end  causes  a 
marked  fall  of  blood-pressure  (p.  183),  accompanied  by,  but  not 
essentially  due  to,  a  distinct  slowing  of  the  heart.  If  the  animal  is 
not  anaesthetized,  there  may  be  signs  of  pain,  and  for  this  reason  the 
depressor  has  sometimes  been  spoken  of,  somewhat  loosely,  as  the 
sensory  nerve  of  the  heart.  The  abdominal  sympathetic  (of  the 
frog)  also  contains  afferent  fibres,  through  which  reflex  inhibition  of 
the  heart  can  be  produced  when  they  are  excited  mechanically  by  a 
rapid  succession  of  light  strokes  on  the  abdomen  with  the  handle 
of  a  scalpel. 

On  the  other  hand,  when  the  central  end  of  an  ordinary  peripheral 
ne:ve  like  the  sciatic  or  brachial  is  excited,  the  common  effect  is  pure 
augmentation  (Fig.  78),  which  sometimes  develops  itself  with  even 
greater  suddenness  than  when  the  accelerator  nerves  are  directly 
stimulated.  Occasionally,  however,  the  augmentation  is  abruptly 
followed  by  a  typical  vagus  action.  Here  the  reflex  inhibitory  effect 
seems  to  break  in  upon  and  cut  short  the  reflex  augmentor  effect. 


THE  NERVOUS  REGULATION  OF  THE  HEART  t6g 

These  examples  show  that  certain  afferent  nerves  are  especially 
related  to  the  cardio-inhibitory,  and  others  to  the  cardio-augmentor, 
centre,  or  at  least  that  the  central  connections  of  some  nerves  are 
such  that  inhibition  is  the  usual  effect  of  their  reflex  excitation, 
while  the  opposite  is  the  case  with  other  nerves.  But  it  is  im- 
probable that  the  effect  of  a  stream  of  afferent  impulses  reaching 
ihe  cardiac  centres  by  any  given  nerve  is  determined  solely  by 
anatomical  relations.  The  intensity  and  the  nature  of  the  stimulus 
seem  also  to  have  something  to  do  \vith  the  result.  For  when 
ordinary  sensory  nerves  are  weakly  stimulated,  augmentation  is 
said  to  be  more  common  than  inhibition,  'and  the  opposite  when 
they  are  strongly  stimulated.  And  while  a  chemical  stimulus,  hke 
the  inhaled  vapour  of  chloroform  or  ammonia,  causes  in  the  rabbit 


Fig  78.— Myocardiographic  Tracing  of  Cat's  Ventricle.  The  signal  line  shows  the 
point  at  which  the  central  end  of  the  brachial  nerve  was  stimulated  during 
resuscitation  of  the  animal  after  a  period  of  cerebral  anaemia.  Some  augmenta- 
tion of  the  ventricular  beat  is  seen.  The  notches  in  the  ventricular  tracing  are 
due  to  the  artificial  respiration.     Time-trace,  seconds. 

reflex  inhibition  of  the  heart  through  the  fibres  of  the  trigeminus 
that  confer  common  sensation  on  the  mucous  membrane  of  the  nose, 
the  mechanical  excitation  of  the  sensory  nerves  of  the  pharynx 
and  oesophagus  when  water  is  slowly  sipped  causes  acceleration.* 
The  stimulation  of  the  nerves  of  special  sense  is  followed  sometimes 
by  the  one  effect  and  sometimes  by  the  other.  To  complete  the 
catalogue  of  the  nervous  channels  by  which  impulses  may  reach  the 
cardiac  centres  in  the  medulla,  we  may  add  that  there  must  be  an 
extensive  connection  between  them  and  the  cerebral  cortex,  since 
every  passing  emotion  leaves  its  trace  upon  the  curve  of  cardiac 
action.  The  so-called  '  reflex  cardiac  death,'  which  is  an  occasional 
consequence  of  intense  psychical  influences  (anxiety,  fright,  etc.), 

•  In  78  healthy  students  the  average  pulse-rate   (in  the  sitting  positionj 
was  increased  from  73  to  85  per  minute  by  sipping  water. 


lyo  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

may  be  due  to  the  prolonged  excitation  of  the  cardio-inhibitory 
centre,  as  well  as  to  the  disturbance  of  other  centres  in  the  bulb  by 
the  cortical  storm.  It  is  a  remarkable  fact,  too,  and  one  that  can 
only  be  explained  by  such  a  connection,  that  although  in  the  vast 
majority  of  individuals  the  will  has  no  influence  whatever  on  the 
rate  or  force  of  the  heart,  except,  perhaps,  indirectly  through  the 
respiration,  some  persons  have  the  power,  by  a  voluntary  effort,  of 
markedly  accelerating  the  pulse.  In  one  case  of  this  kind  it  was 
noticed  that  perspiration  broke  out  on  the  hands  and  other  parts  of 
the  body  when  the  heart  was  voluntarily  accelerated.  A  rise  of 
blood-pressure  due  to  constriction  of  the  vessels  has  also  been 
observed.  The  effort  cannot  be  kept  up  for  more  than  a  short  time, 
and  the  pulse-rate  quickly  goes  back  to  normal.  It  has  been 
recently  shown  that  this  peculiar  power  is  more  common  than  has 
been  supposed,  and  that  where  it  is  present  in  rudiment  it  can  be 
cultivated,  although  it  is  a  dangerous  acquisition. 

As  an  example  of  the  direct  action  on  a  cardiac  centre  of  a 
changed  chemical  composition  of  the  blood,  we  may  cite  the 
inhibition  produced  by  injection  of  bile  into  a  vein  and  revealed 
in  the  slow  pulse  of  many  cases  of  jaundice;  and  as  an  instance 
of  the  direct  action  of  a  physical  change,  the  slowing  of  the  heart 
as  the  blood-pressure  rises  (p.  i86)  in  asphyxia  or  on  clamping  the 
aorta.  The  variation  in  the  pulse-rate  associated  with  changes 
in  the  position  of  the  body,  to  which  we  have  already  referred 
(p.  107),  is  brought  about  by  direct  stimulation  of  the  in- 
hibitory centre  by  the  increase  of  blood-pressure  in  the  medulla 
oblongata  when  a  person  who  has  been  standing  assumes  the  supine, 
or  even  the  sitting,  posture.  But  it  is  also  due  in  part  to  changes  in 
the  amount  of  muscular  contraction,  since  muscular  exercise  causes 
acceleration  of  the  heart  either  reflexly,  through  afferent  muscular 
nerves,  or  by  a  direct  effect  of  waste  products  of  the  metabolism  of 
the  muscles  on  the  cardiac  centres  in  the  bulb  or  on  the  heart  itself 

(P-275)- 

Theoretically,  quickening  of  the  heart  might  be  caused  either  by 
a  diminution  in  the  inhibitory  tone  or  by  an  increase  in  the  activity 
of  the  augmentor  centre;  and  slowing  of  the  heart  might  be  due 
either  to  a  diminution  in  the  augmentor  tone,  if  such  exists,  or  to 
an  increase  in  the  activity  of  the  inhibitory  centre.  So  that  it  is 
not  always  easy  to  interpret  such  results  as  we  have  quoted  above. 
But  it  would  appear  that  under  ordinary  conditions  the  rate  of  the 
heart  is  mainly  regulated  by  the  inhibitory  centre,  which,  within  a 
considerable  range,  can  produce  variations  in  either  direction.  The 
augmentor  mechanism  is  perhaps  merely  auxiUary  to  the  inhibitory, 
being  called  into  action  only  in  emergencies. 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      171 


Section  VI. — The  Nervous  Regulation  of  the  Bloodvessels 
(Vaso-Motor  Nervesj. 

Just  as  the  muscular  walls  of  the  heart  are  governed  by  two  sets 
of  nerve-fibres,  a  set  which  keeps  down  the  rate  of  worlang  and  a 
set  which  may  increase  it,  the  muscular  walls  of  the  vessels  are  under 
the  control  of  nerves  which  have  the  power  of  diminishing  their 
calibre  (vaso-constrictor),  and  of  nerves  which  have  the  power  of 
increasing  it  (vaso-dilator).  All  nerves  that  effect  the  caUbre  of  the 
vessels,  whether  vaso-constrictor  or  vaso-dilator,  are  included  under 
the  general  name  vaso-motor.  These  vaso-motor  nerves,  like  the 
augmentor  and  inhibitory  fibres  of  the  heart,  are  connected  with  a 
centre  or  centres,  which  in  turn  are  in  relation  with  numerous  afterent 
nerves.  It  is  convenient  to  distinguish  the  afferent  nerves  which 
cause  on  the  whole  a  vaso-constriction  and  a  consequent  increase 
of  arterial  pressure  as  pressor  nerves,  and  those  which  cause  on  the 
whole  vaso- dilatation,  with  fall  of  pressure,  as  depressor  nerves, 
reserving  the  terms  vaso-constrictor  and  vaso-dilator  for  the  efferent 
portions  of  the  reflex  arcs.  It  is  through  this  reflex  mechanism 
that  the  bloodvessels  are  mainly  influenced,  although  the  endings 
of  the  vaso-motor  nerves  in  the  smooth  muscular  fibres  or  the 
muscular  fibres  themselves  are  sometimes  directly  affected  by  sub- 
stances circulating  in  the  blood.  Proteoses,  for  instance,  cause  by 
peripheral  action  dilatation  of  the  vessels  and  a  fall  of  blood-pressure 
(p.  213);  suprarenal  extract,  or  its  active  principle,  adrenalin,  or 
epinephrin,  constriction,  with  a  rise  of  pressure  (pp.  214,  638).  Apo- 
codeine  paralyzes  the  vaso-motor  nerve-endings  after  a  preliminary 
stimulation,  and  now  adrenalin  causes  no  constriction.  Chryso- 
toxin,  an  active  principle  of  ergot,  causes  a  marked  rise  of  blood- 
pressure  b}'  stimulating  the  sympathetic  ganghon-cells  or  the  pre- 
ganglionic fibres  of  the  vaso-constrictor  path.  Vaso-motor  nerves 
control  chiefly  the  small  arteries.  They  have  no  direct  influence  on 
the  capillaries.*  Nor  has  the  existence  of  an  eft'ective  vaso-motor 
regulation  of  the  calibre  of  the  veins,  except  in  the  portal  system, 
been  proved  up  to  this  time  by  any  clear  and  unambiguous  experi- 
ment, although  there  are  grounds  on  which  it  has  been  surmised 
that  the  nervous  system  does  influence  the  '  tone  '  of  the  whole 
venous  tract.     These  grounds  will  be  mentioned  in  the  proper  place. 

*  It  is  usually  taught  that  the  capillaries,  being  devoid  of  muscular  fibres 
in  their  walls,  are  not  supplied  with  vaso-motor  fibres,  and  that  the  only  kind 
of  active  contraction  of  which  they  are  capable  is  due  to  a  process  analogous 
to  the  turgescence  of  vegetable  cells,  the  thickness  of  the  wall  being  increased 
at  the  expense  of  the  lumen,  while  the  total  cross-section  of  the  vessel  remains 
unchanged.  It  has  been  asserted,  however,  that  a  true  contraction,  in  which 
both  the  total  section  and  the  lumen  are  diminished,  may  be  caused  in  the 
capillaries  of  the  nictitating  membrane  of  the  frog  either  by  direct  stimulation 
or  by  excitation  of  vaso-motor  fibres  in  the  sympathetic  (Steinach  and  Kahn). 


172  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

Meanwhile,  before  describing  the  distribution  of  the  best-known 
tracts  of  vaso-motor  fibres  and  defining  the  position  of  the  vaso- 
motor centres,  we  must  glance  at  the  methods  by  which  our  know- 
ledge has  been  attained. 

(i)  In  translucent  parts  inspection  is  sufficient.  Paling  of  the  part 
indicates  constriction;  flushing,  dilatation  of  the  small  vessels.  This 
method  has  been  much  used,  sometimes  in  conjunction  with  (2),  in  such 
parts  as  the  balls  of  the  toes  of  dogs  or  cats,  the  ear  of  the  rabbit,  the 
conjunctiva,  the  mucous  membrane  of  the  mouth  and  gums,  the  web  of 
the  frog,  the  wing  of  the  bat,  the  intestines,  etc. 

(2)  Observation  of  changes  in  the  temperature  of  parts.  This  method 
has  been  chiefly  employed  in  investigating  the  vaso-motor  nerves  of 
the  limbs,  the  thermometer  bulb  being  fixed  between  the  toes.  In  such 
peripheral  parts  the  temperature  of  the  blood  is  normally  less  than  that 
of  the  blood  in  the  internal  organs,  because  the  opportunities  of  cooling 
are  greater.  The  effect  of  a  freer  circulation  of  blood  (dilatation  of  the 
arteries)  is  to  raise  the  temperature ;  of  a  more  restricted  circulation 
(constriction  of  the  arteries),  to  lower  it. 

(3)  Measurement  of  the  blood-pressure.  If  we  measure  the  arterial 
blood-pressure  at  one  point,  and  find  that  stimulation  of  certain  nerves 
increases  it  without  affecting  the  action  of  the  heart,  we  can  conclude 
that  upon  the  whole  the  tone  of  the  small  vessels  has  been  increased. 
But  we  cannot  tell  in  what  region  or  regions  the  increase  has  taken  place ; 
nor  can  we  tell  whether  it  has  not  been  accompanied  by  diminution  of 
tone  in  other  tracts. 

But  if  we  measure  simultaneously  the  blood-pressure  in  the  chief 
artery  and  chief  vein  of  a  part  such  as  a  limb,  we  can  tell  from  the 
changes  caused  by  section  or  stimulation  of  nerves  whether,  and  in 
what  sense,  the  tone  of  the  small  vessels  within  thisarea  has  been  altered. 
For  example,  if  we  found  that  the  lateral  pressure  in  the  artery  was 
diminished,  while  at  the  same  time  it  was  increased  in  the  vein,  we 
should  know  that  the  '  resistance  '  between  artery  and  vein  had  been 
lessened,  and  that  the  blood  now  found  its  way  more  readily  from  the 
artery  into  the  vein.  If,  on  the  other  hand,  the  venous  pressure  was 
diminished,  and  the  arterial  pressure  simultaneously  increased,  we  should 
have  to  conclude  that  the  vascular  resistance  in  the  part  was  greater 
than  before.  If  the  pressure  both  in  artery  and  vein  was  increased,  we 
could  not  come  to  any  conclusion  as  to  local  changes  of  resistance  with- 
out knowing  how  the  general  blood-pressure  had  varied. 

(4)  The  measurement  of  the  velocity  of  the  blood  in  the  vessels  of 
the  part.  This  may  be  done  by  the  stromuhr  or  dromograph,  or  by 
allowing  the  blood  to  escape  from  a  small  vein  and  measuring  the 
outflow  in  a  given  time,  or,  without  opening  the  vessels,  by  estimating 
the  circulation-time  (p.  135).  When  changes  in  the  general  arterial 
pressure  are  eliminated,  slowing  of  the  blood-stream  through  a  part 
corresponds  to  increase  of  vascular  resistance  in  it ;  increase  in  the  rate 
of  flow  implies  diminished  vascular  resistance .  Sometimes  the  red  colour 
of  the  blood  issuing  from  a  cut  vein,  and  the  visible  pulse  in  the  stream, 
indicate  with  certainty  that  the  vessels  of  the  organ  have  been  dilated. 

(5)  Alterations  in  the  volume  of  an  organ  or  limb  are  often  taken  as 
indications  of  changes  in  the  calibre  of  the  small  vessels  in  it.  We 
have  already  seen  how  these  alterations  are  recorded  by  means  of  a 
plethysmograph  (p.  128).  The  brain  is  enclosed  in  the  skull  as  in  a 
natural  plethysmograph,  and  changes  in  its  volume  may  be  registered 
by  connecting  a  recording  apparatus  with  a  trephine  hole. 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS 


173 


(6)  For  the  separation  of  the  effects  of  stimulation  of  vaso-constrictor 
and  vaso-dilator  fibres  when  they  are  mingled  together,  as  is  the  case 
in  many  nerves,  advantage  is  taken  of  certain  differences  between  them. 
For  example,  the  vaso-constrictors  lose  their  excitability  sooner  than 
the  vaso-dilators  when  cut  off  from  the  nerve-cells  to  which  they  belong. 
So  that  if  a  nerve  is  divided,  and  some  days  allowed  to  elapse  before 
stimulation,  only  the  dilators  will  be  excited.  The  vaso-dilators  are 
more  sensitive  to  weak  stimuli  repeated  at  long  intervals  than  to  strong 
and  frequent  stimuli,  and  the  opposite  is  true  of  the  constrictors.  When 
a  nerve  containing  both  kinds  of  fibres  is  heated,  the  excitability  of 
the  vaso-constrictors  is  increased  in  a  greater  degree  than  that  of  the 
dilators;  when  the  nerve  is  cooled,  the  dilators  preserve  their  excita- 
bility at  a  temperature  at  which  the  constrictors  have  ceased  to  respond 
to  stimulation  (Fig.  79). 

The  Chief  Vaso-Motor  Nerves. — The  first  discovery  of  vaso-motor 
nerves  was  made  in  the  cervical  sympathetic,     \^"hen  this  nerve  is 


Fig.  79. — Plethysmograms :  Hind-Limb  of  Cat  (after  Bowditch  and  Warren).  To  be 
read  from  right  to  left.  On  the  left  hand  is  shown  the  effect  of  slow  stimulation 
of  the  sciatic  (i  per  second);  on  the  right  hand  the  effect  of  rapid  stimulation 
(64  per  second).  In  the  first  case  the  limb  swelled  owing  to  excitation  of  the 
vaso-dilators;  in  the  second,  it  shrank  th/-"ough  excitation  of  the  vaso-constrictors. 

cut,  the  corresponding  side  of  the  head,  and  especially  the  ear, 
become  greatly  injected  owing  to  the  dilatation  of  the  vessels.  This 
experiment  can  be  very  readily  performed  on  the  rabbit,  and  the 
changes  are  most  easily  followed  in  an  albino.  The  ear  on  the  side 
of  the  cut  nerve  is  redder  and  hotter  than  the  other;  the  main 
arteries  and  veins  are  swollen  with  blood,  and  many  vessels  formerly 
invisible  come  into  view.  The  slow  rhythmical  changes  of  calibre, 
which  in  the  normal  rabbit  are  very  characteristically  seen  in  the 
middle  artery  of  the  ear,  disappear  for  a  time  after  section  of  the 
sympathetic,  although  they  ultimately  again  become  visible  (Prac- 
tical E.xercises,  p.  215). 

Stimulation  of  the  cephalic  end  of  the  cut  sympathetic  causes  a 
marked  constriction  of  the  vessels  and  a  fall  of  temperature  on  the 
same  side  of  the  head.     From  these  facts  we  know  that  the  cervical 


174  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

sympathetic  in  mammals  contains  vaso-constrictor  fibres  for  the 
side  of  the  head  and  ear,  and  that  these  fibres  are  constantly  in 
action.  Certain  parts  of  the  eye,  and  the  salivary  glands,  larynx, 
oesophagus,  and  thyroid  gland,  are  also  supplied  with  vaso-motor 
(constrictor)  nerves  from  the  cervical  sympathetic. 

It  has  been  asserted  that  the  cervical  sympathetic  contains  some  of 
the  vaso-constrictor  fibres  that  supply  the  corresponding  half  of  the 
brain  and  its  membranes,  but  this  has  been  disputed,  and  some  ob- 
servers deny  that  the  vessels  oi  the  brain  have  any  vaso-motor  nerves. 
Non-medullated  nerve-fibres,  however,  may  be  seen  in  and  around  the 
walls  of  the  cerebral  and  spinal  bloodvessels,  and  it  is  difficult  to  believe 
that  these  have  not  a  vaso-motor  function,  although  this  has  not  as 
yet  been  clearly  demonstrated  by  experimental  methods. 

It  has  sometimes  been  argued  that  we  ought  not  to  expect  the  brain 
to  be  supplied  with  vaso-motors.  For  it  is  enclosed  in  a  rigid  box,  and 
the  quantity  of  blood  in  it  can  be  increased  or  diminished  only  to  the 
slight  extent  to  which  the  cerebro-spinal  liquid  can  be  displaced  into 
the  vertebral  canal.  Important  changes  in  the  cerebral  blood-supply 
are  therefore  brought  about,  it  is  said,  not  by  a  widening  or  narrowing 
of  the  cerebral  vessels,  but  by  an  alteration  in  the  velocity  of  the  blood 
in  them  as  a  result  of  a  rise  or  fall  of  the  systemic  arterial  pressure. 
This  argument,  however,  leaves  out  of  account  the  consideration  that 
in  general  the  brain  does  not  function  as  a  whole,  but  that  certain 
parts  of  it  may  often  become  active  and  relatively  hyperaemic,  while 
other  parts  are  inactive  and  relatively  anaemic,  and  that  important 
changes  in  the  distribution  of  the  blood  in  the  encephalon  may  be 
effected,  although  the  total  mass  of  blood  in  the  organ  undergoes  little 
or  no  alteration.  It  is,  of  course,  true  that  it  is  not  the  absolute  quantity 
of  blood  in  an  organ  which  is  a  function  of  its  activity,  but  the  rate  at 
which  it  is  renewed.  And  it  is  theoretically  possible  that  an  organ  at 
rest  should  contain  as  much  blood  as  when  it  is  active,  or  even  more. 
But  such  cases,  if  they  exist,  are  certainly  rare.  The  fact  that  adrenalin 
generally  constricts  the  vessels  of  a  perfused  brain  (Wiggers)  is  in  favour 
of  the  existence  of  vaso-motors.  The  retina,  which  from  the  stand- 
point of  development  is  a  portion  of  the  brain,  is  undoubtedly  supplied 
with  vaso-constrictor  fibres  which  run  in  the  cervical  sympathetic. 

That  the  cervical  sympathetic  contains  some  dilator  fibres  is 
proved  by  the  fact  that  stimulation  of  the  cephaHc  end  in  the  dog 
causes  flushing  of  the  mucous  membrane  of  the  mouth  on  the  same 
side.  Further,  after  division  of  the  nerve  on  one  side  in  the  rabbit 
it  may  be  observed  that  when  the  animal  is  excited  the  vessels  of  the 
ear  whose  nerve  is  intact  may  become  still  more  dilated  than  those 
whose  constrictor  fibres  have  been  paralyzed.  The  only  explana- 
tion is  that  vaso- dilators  are  being  excited  from  the  central  nervous 
system.  In  the  cat  the  cervical  sympathetic  contains  vaso-dilators 
for  the  submaxillary  gland  (p.  386). 

The  vaso-motor  fibres  of  the  head  run  up  in  the  cervical  sympa- 
thetic, and  then  pass  into  various  cerebral  nerves,  of  which  the  fifth 
or  trigeminus  is  the  most  important. 

The  trigeminus  nerve  contains  vaso-constrictor  nerves  for  various 
parts  of  the  eye  (conjunctiva,  sclerotic,  iris),  and  for  the  mucous 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      175 

membrane  of  the  nose  and  gums,  and  section  of  it  is  followed  by 
dilatation  of  the  vessels  of  these  regions.  The  lingual  branch  of 
the  trigeminus  supplies  vaso-motor  fibres  to  the  tongue,  and  ap- 
parently both  vaso-constrictor  and  vaso-dilator. 

In  some  animals — the  rabbit,  for  instance — the  ear  derives  part 
of  its  vaso-motor  supply  through  the  great  auricular  nerve,  a  branch 
of  the  third  f^ervical  nerve,  which  they  reach  as  grey  rami  from  the 
stellate  ganglion. 

Another  great  vaso-motor  tract,  the  most  influential  in  the  body, 
is  contained  in  the  splanchnic  nerves,  which  govern  the  vessels  of 
many  of  the  abdominal  organs.  Section  of  these  nerves  causes  an 
immediate  and  sharp  fall  of  arterial  pressure.  The  intestinal  vessels 
are  dilated  and  overfilled  with  blood.  As  a  necessary  consequence 
of  their  immense  capacity,  the  rest  of  the  vascular  system  is  under- 
filled, and  the  blood-pressure  falls  accordingly.  Stimulation  of  the 
peripheral  end  of  the  splanchnic  nerves  causes  a  great  rise  of  blood- 
pressure,  owing  to  the  constriction  of  vessels  in  the  intestinal  area. 
We  therefore  conchide  that  in  the  splanchnics  there  are  vaso-motor 
fibres  of  the  constrictor  type,  and  that  impulses  are  constantly 
passing  down  them  to  maintain  the  normal  tone  of  the  vascular 
tract  which  they  command.  When  the  splanchnic  nerves  are 
stimulated,  the  adrenal  glands  are  so  affected  that  adrenahn  passes 
out  by  the  veins  into  the  blood-stream.  It  is  clear  that  if  the  quan- 
tity thus  liberated  were  sufficiently  large  and  its  liberation  suffi- 
ciently prompt  it  might  play  a  part  in  the  rise  of  pressure  (p.  640) 
which  follows  stimulation  of  the  nerves,  whether  they  are  excited 
directly  or  in  the  normal  course  of  events  reflexly.  But  it  has  not 
been  demonstrated  that  this  is  an  effective  factor.  Dilator  fibres 
(for  the  intestines  and  the  kidney,  for  example)  have  also  been 
discovered  in  the  splanchnic  nerves,  although  the  constrictors 
predominate,  and  special  methods  have  to  be  employed  for  the 
detection  of  the  dilators. 

The  same  is  true  of  the  nerves  of  the  extremities,  which  certainly 
contain  vaso-dilator  fibres  in  addition  to  vaso-constrictors,  although 
the  difficulty  of  demonstrating  the  presence  of  the  former  is  fully 
as  great  as  it  is  in  the  splanchnics.  For  the  investigation  is  com- 
phcated  by  the  fact  that  such  nerves  as  the  sciatic  supply  with 
vaso-motor  fibres  two  leading  tissues — skin  and  muscle;  and  these 
are  not  necessarily  affected  in  the  same  direction  or  to  the  same 
extent  by  stimulation  of  their  vaso-motor  fibres.  The  vaso-con- 
strictors under  ordinary  conditions  preponderate,  so  that  section  of 
the  sciatic  or  the  brachial  is  generally  followed  by  flushing  of  the 
balls  of  the  toes  and  rise  of  temperature  of  the  feet,  stimulation  by 
paling  and  fall  of  temperature.  By  taking  advantage,  however,  of 
the  unequal  excitability  of  dilators  and  constrictors  in  a  degenerating 
nerve,  and  of  the  differences  between  the  two  kinds  of  fibres  in  their 


176  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPIi 

reaction  to  electrical  stimuli  (p.  173),  it  has  been  shown  that  vaso- 
dilators are  also  present,  and  come  to  the  front  when  the  conditions  are 
rendered  favourable  for  them  and  unfavourable  for  the  constrictors. 

Vaso-motor  fibres  for  the  fore-limb  (dog)  issue  from  the  cord  in  the 
anterior  roots  of  the  third  to  the  eleventh  dorsal  nerves,  and  for  the 
hind-limb  in  the  anterior  roots  of  the  eleventh  dorsal  to  the  third  lumbar. 
Stimulation  of  most  of  these  roots  causes  constriction  of  the  vessels, 
but  stimulation  of  the  eleventh  dorsal  may  cause  dilatation  (Bayliss 
and  Bradford). 

The  V aso-M otor  Nerves  of  Muscle. — When  the  motor  nerve  of  the  thin 
mylo-hyoid  muscle  of  the  frog,  which  can  be  observed  under  the  micro- 
scope, is  cut,  and  the  peripheral  end  stimulated,  the  vessels  are  seen  to 
dilate  distinctly,  and  this  effect  is  not  abolished  when  contraction  of 
the  muscle  is  prevented  by  a  dose  of  curara  insufficient  to  paralyze  the 
vaso-motor  nerves.  This  indicates  the  existence  in  the  nerve  of  vaso- 
dilator fibres.  But  we  must  be  cautious  in  transferring  this  result  to 
ordinary  skeletal  muscle,  for  the  mylo-hyoid  is  more  closely  allied  to 
the  muscles  of  the  tongue  than,  for  example,  to  the  muscles  of  the  limbs, 
and  in  the  mammal  the  tongue  muscles  are  known  to  be  better  supplied 
with  vaso-dilator  fibres  than  the  limb  muscles.  The  average  flow  of 
blood  through  a  mammalian  muscle  is  indeed  increased  during  volun- 
tary contraction,  and  during  rhythmically  repeated  artificial  tetaniza- 
tion  of  its  motor  nerve.  The  outflow  of  blood  from  the  main  vein  of 
the  levator  labii  superioris,  one  of  the  muscles  used  in  feeding  in  the 
horse,  was  found  to  be  in  one  experiment  nearly  eight  times,  in  another 
about  seven  times,  and  in  a  third  three  and  a  half  times  as  great  during 
voluntary  work  with  it  (in  chewing)  as  in  rest.  But  as  no  increase  in 
the  blood-flow  through  the  skeletal  muscles  of  a  completely  curarized 
mammal  during  excitation  of  their  nerves  has  ever  been  satisfactorily 
demonstrated,  we  must  conclude  that  they  are  very  scantily  provided 
with  vaso-dilator  fibres  or  not  at  all.  It  is  uncertain  whether  they  are 
supplied  with  vaso-constrictors.  The  undoubted  increase  in  the  blood- 
flow  in  contraction  may  therefore  be  connected  in  some  way  with  the 
mechanical  or  chemical  changes  in  the  muscular  fibres  themselves. 

It  has  been  suggested  that  the  muscular  vessels  are  widened  by  the 
direct  action  of  the  acid  products  of  the  active  muscle,  since  very  dilute 
acids  (lactic  acid,  e.g.)  cause  general  dilatation  of  the  small  vessels. 
A  similar  explanation  has  been  extended  to  the  dilatation  of  the  vessels 
of  the  brain  during  cerebral  activity  by  some  of  those  who  deny  the 
existence  of  vaso-motor  nerves  for  that  organ,  but  here  the  evidence 
is  by  no  means  satisfactory.  The  vagus  has  been  stated  to  contain 
vaso-constrictor,  and  the  annulus  of  Vieussens  vaso-dilator,  fibres  for 
the  coronary  arteries  of  the  heart.  But  this  question  is  far  from  being 
settled.  Adrenalin  causes  dilatation  and  not  constriction  of  the 
coronary  vessels.  There  is  some  reason  to  believe  that  the  metabolic 
products  liberated  in  the  heart-muscle,  e.g.,  carbon  dioxide,  govern  the 
changes  in  the  calibre  of  the  coronary  arterioles.  A  close  relationship 
exists  between  the  output  of  carbon  dioxide  and  the  rate  of  flow  through 
the  coronary  circulation.  In  asphyxia  the  flow  through  the  coronary 
vessels  is  notably  increased;  indeed,  it  is  at  its  maximum  just  before 
the  heart  fails  altogether,  as  if  an  effort  were  being  made  to  keep  the 
heart  going  to  the  last  by  making  up  to  it  in  the  quantity  of  the  blood 
supplied  what  it  lacks  in  quality.  As  this  increased  flow  is  seen  in  the 
isolated  heart-lung  preparation,  it  has  been  concluded  that  metabolites 
produced  in  the  cardiac  muscle  itself  cause  an  increased  coronary  flow 
when  increased  demands  are  made  on  the  heart,  a  local  regulative 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS     177 

mechanism  being  thus  constituted.     There  is  some  evidence  that  carbon 
dioxide  is  not  the  most  potent  of  these  substances. 

Vaso-Motor  Nerves  of  the  Lungs. — There  has  been  much  discussion  as 
to  the  course,  and  even  as  to  the  existence,  of  vaso-motor  fibres  for  the 
lungs.  The  problem  is  perhaps  the  most  difficult  in  the  whole  range  of 
vaso-motor  topography,  for  the  pulmonary  circulation  is  so  related  to 
other  vascular  tracts,  that  changes  produced  in  the  vessels  of  distant 
organs  by  the  stimulation  or  section  of  nerves  may  affect  the  quantity 
of  blood  received  by  the  right  side  of  the  heart,  and  therefore  the 
quantity  propelled  through  the  lungs  and  the  pressure  in  the  pulmonary 
artery.  And  changes  in  the  systemic  arterial  pressure  may  favour  or 
hinder  the  discharge  of  the  left  ventricle,  and  therefore  affect  the  pres- 
sure in  the  left  auricle  and  the  pulmonary  veins.  Nevertheless,  evidence 
has  been  obtained  from  a  number  of  sources  that  the  lungs  are  supplied 
with  vaso-constrictor  fibres.  Plumicr,  perfusing  isolated,  '  surviving  ' 
lungs  with  blood  under  constant  pressure  and  measuring  the  outflow, 
showed  that  adrenalin  and  also  stimulation  of  the  annulus  of  Vieussens 
caused  great  diminution  in  the  flow — that  is,  constriction  of  the  vessels. 
Wiggers  also  obtained  constriction  with  adrenalin.  Fiihner  and 
Starling,  working  with  a  preparation  including  the  heart  as  well  as  the 
lungs,  found  that  adrenalin  caused  a  rise  of  pressure  in  the  pulmonary 
artery  coupled  with  a  fall  of  pressure  in  the  left  auricle,  which  could 
only  be  due  to  constriction  of  the  vessels  of  the  lungs.  It  is  assumed 
that  adrenalin  produces  vaso-constriction  only  in  vessels  supplied  with 
vaso-constrictor  nerves  (p.  638),  and  that  in  organs  where  this  substance 
does  not  cause  vaso-constriction  no  such  fibres  are  present.  In  mam- 
mals the  vaso-constrictor  fibres  seem  to  pass  out  from  the  upper  half 
of  the  dorsal  spinal  cord,  and  some  of  them  can  be  detected  nearer  their 
destination  in  the  annulus  of  Vieussens.  The  vago-sympathctic  of  the 
tortoise  contains  vaso-constrictors  for  the  lung  of  the  same  side  (Krogh). 

Vaso-Dilator  Fibres. — In  most  of  the  peripheral  nerves  these  are 
mingled  with  vaso-constrictors;  but  in  certain  situations,  for  an 
anatomical  reason  that  will  be  mentioned  presently,  nerves  exist  in 
which  the  only  vaso-motor  fibres  are  of  the  dilator  type.  Of  these, 
the  most  conspicuous  examples  are  the  chorda  tympani  and  the 
nervi  erigentes  or  pelvic  nerves;  and,  indeed,  it  was  in  the  chorda 
that  vaso-dilators  were  first  discovered  by  Bernard.  The  chorda 
tympani  contains  vaso-dilator  and  secretory  fibres  for  the  sub- 
maxillary and  sublingual  salivary  glands.  With  the  secretory  fibres 
we  have  at  present  nothing  to  do;  and  the  whole  subject  will  have 
to  be  returned  to,  and  more  fully  discussed  in  Chapter  VI.  But  a 
most  marked  vascular  change  is  produced  by  stimulation  of  the 
peripheral  end  of  the  divided  chorda  tympani  nerve.  The  glands 
flush  red;  more  blood  is  evidently  passing  through  their  vessels. 
Allowed  to  escape  from  a  divided  vein,  the  blood  is  seen  to  be  of  a 
bright  arterial  colour  and  shows  a  distinct  pulse.  The  small  arteries 
have  been  dilated  by  the  action  of  the  vaso-motor  fibres  in  the  nerve. 
The  resistance  being  thus  reduced,  the  blood  passes  in  a  fuller  and 
more  rapid  stream  through  the  capillaries  into  the  veins,  and  on  the 
way  there  is  not  time  for  it  to  become  completely  venous.  These 
vaso-dilator  fibres  are  not  in  constant  action,  for  section  of  the 

12 


178  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

nerve,  as  a  rule,  produces  little  or  no  change.  Vaso-constrictor 
fibres  pass  to  the  salivary  glands  from  the  cervical  sympathetic 
along  the  arteries,  and  stimulation  of  that  nerve  causes  narrowing  of 
th  ?  vessels  and  diminution  of  the  blood- flow,  sometimes  almost  to 
complete  stoppage. 

The  nervi  erigentes  are  the  nerves  through  wiiich  erection  of  the 
penis  is  caused.  When  they  are  divided  there  is  no  effect,  but 
stimulation  of  the  peripheral  end  causes  dilatation  of  the  vessels  of 
the  erectile  tissue  of  the  organ,  which  becomes  overfilled  with 
blood.  During  stimulation  of  these  nerves,  the  quantity  of  blood 
flowing  from  the  cut  dorsal  vein  of  the  penis  may  be  fifteen  times 
greater  than  in  the  absence  of  stimulation.  It  spurts  out  in  a  strong 
stream,  and  is  brighter  than  ordinary  venous  blood  (Eckhard). 
Stimulation  of  the  peripheral  end  of  the  nervus  pitdendus  causes 
constriction  of  the  vessels  of  the  penis,  so  that  it  contains  vaso- 
constrictor fibres  which  are  the  antagonists  of  the  nervi  erigentes. 

Vaso-Motor  Nerves  of  Veins. — Like  arteries,  veins  have  plexuses 
of  nerve-fibres  in  their  walls,  and  contract  in  response  to  various 
stimuli.  In  some  cases — e.g.,  in  the  wing  of  the  bat — rhythmical 
contractions  of  the  veins  are  strikingly  displayed,  but  they  do  not 
depend  on  the  central  nervous  system,  as  they  persist  after  section 
of  the  brachial  nerves.  The  first  clear  proof  of  the  existence  of 
vaso-motor  nerves  for  veins  was  furnished  by  Mall,  who  showed 
that  vaso-constrictor  fibres  for  the  portal  vein  exist  in  the  splanchnic 
nerves.  When  these  were  stimulated,  after  the  disturbing  effect  of 
changes  in  the  circulation  through  the  intestines  had  been  eliminated 
by  compression  of  the  aorta  in  the  thorax,  an  actual  shrinking  of 
the  vein  could  be  observed.  The  fibres  issue  from  the  spinal  cord 
by  the  anterior  roots  of  the  third  to  the  eleventh  dorsal  nerves,  but 
chiefly  in  the  fifth  to  the  ninth  dorsal.  When  the  liver  is  enclosed 
in  a  plethysmograph,  and  the  central  end  of  an  ordinary  sensory 
nerve,  like  the  sciatic,  excited,  reflex  vaso-constriction  takes  place 
in  the  portal  area,  the  volume  of  the  organ  diminishes,  and  the 
blood-pressure  rises  in  the  portal  vein  (Fran^ois-Franck). 

The  vena  portae  and  its  branches  are  in  the  physiological  sense 
arteries  rather  than  veins,  since  they  break  up  into  capillaries,  and 
it  was  to  be  expected  that  the  regulation  of  the  blood-flow  in  them 
would  be  carried  out  in  the  same  way  as  in  ordinary  arteries,  namely, 
by  means  of  vaso-motor  nerves.  But  we  must  not,  without  special 
proof,  extend  the  results  obtained  in  the  portal  system  to  ordinary 
veins.  A  certain  amount  of  evidence,  however,  exists  that  even 
such  veins  as  those  of  the  extremities  are  supplied,  though  scantily, 
with  vaso-constrictor  (veno-motor)  fibres.  After  ligation  of  the 
crural  artery  or  aorta,  stimulation  of  the  peripheral  end  of  the 
sciatic  has  been  seen  to  cause  contraction  of  short  portions  of  the 
superficial  veins  of  the  leg. 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      179 

Finally,  adrenalin  (epinephrin)  causes  constriction  of  rings  of 
'  surviving  '  veins  just  as  of  artery  rings,  although  in  correspondence 
with  the  smaller  amount  of  muscular  tissue  in  the  former  the  con- 
traction is  not  so  strong.  As  adrenalin  is  assumed  to  act  only  upon 
muscle  supphed  by  s^-m pathetic  nerve-fibres  (p.  638),  this  would 
seem  to  indicate  the  existence  of  such  a  supply  for  veins.  The 
question  is  an  important  one  in  connection  with  the  regulation  of 
the  filling,  and  therefore  of  the  discharge,  of  the  heart  (Henderson), 
but  the  experimental  data  are  as  yet  too  meagre  to  justify'  further 
discussion  of  the  matter  here. 

Course  of  the  Vaso-Motor  Nerves. — In  the  dog  the  vaso-constrictors 
pass  out  as  fine  medullated  fibres  (i'8  to  3-6  /x  in  diameter)  in  the 
anterior  roots  of  the  second  dorsal  to  about  the  second  lumbar  nerves. 
They  proceed  by  the  white  rami  communicantcs  to  the  lateral  sym- 
pathetic ganglia,  where,  or  in  more  distal  ganglia  such  as  the  inferior 
mesenteric,  they  lose  their  medulla,  and  their  axis-cylinder  processes 
(p.  822)  break  up  into  fibrils  that  come  into  close  relation  with 
the  nerve-cells  of  the  ganglia.  These  ganglion-cells  in  their  turn  send 
off  axis-cylLader  processes,  which,  enveloped  by  a  neurilemma,  pass  as 
non-medullated  fibres  by  various  routes  to  their  final  destination,  the 
unstriped  muscular  fibres  of  the  bloodvessels.  Their  course  to  the  head 
has  been  already  described.  To  the  limbs  they  are  distributed  in  the 
great  nerves  (brachial  plexus,  sciatic,  etc.),  which  they  reach  from  the 
sympathetic  ganglia  by  the  grey  rami  communic antes. 

The  outflow  of  vaso-dilator  fibies  is  not  restricted  to  the  same  portion 
of  the  cord  from  which  the  outflow  of  constrictor  fibres  takes  place. 
Their  existence  is  indeed  most  easily  demonstrated  in  ner\'es  springing 
from  those  regions  of  the  cerebro-spinal  axis  from  which  vaso-constrictor 
fibres  do  not  arise,  and  where,  therefore,  we  have  not  to  contend  with 
the  difficulty  of  interpreting  mixed  effects.  Vaso-dilators  for  the 
external  generative  organs  and  the  mucous  membrane  of  the  lower  end 
of  the  rectum  pass  out  as  small  medullated  fibres  of  the  anterior  roots 
of  certain  of  the  sacral  ner\'es  (mainly  the  second  and  third  in  the  cat) 
into  the  pelvic  nerve  (nervus  erigens).  They  end  in  relation  with 
ganglion-cells  in  the  neighbourhood  of  the  organs  which  they  supply. 
The  seventh  and  ninth  cranial  nerves  carry  vaso-dilator  fibres  which 
are  distributed  by  way  of  the  lingual  and  other  branches  of  the  fifth 
to  the  salivary  glands,  the  tongue,  the  mucous  membrane  of  the  floor 
of  the  mouth,  and  part  of  the  soft  palat,o.  Those  in  the  lingual,  passing 
through  the  chorda  tympani,  end  in  gartgl ion-cells  new  the  submaxillary 
and  sublingual  glands,  and  the  axons  of  these  cells  continue  the  path 
to  the  vessels  of  the  glands.  It  is  supposed  that  the  vaso-dilators  dis- 
tributed in  other  branches  of  the  fifth  also  have  ganglion-cells  on  their 
course.  In  fact,  there  is  good  evidence  that  ever}'  efferent  vaso-motor 
fibre  is  interrupted  by  one,  and  only  by  one,  ganglion-cell  between  the 
cord  and  the  bloodvessels.  The  statement  has  been  made  that  for 
certain  regions  of  the  body,  especially  the  skin  of  the  limbs,  the  vaso- 
dilator nerves  arc  contained,  not  in  the  anterior,  but  in  the  posterior 
roots.  And  these,  it  is  claimed,  are  not  aberrant  efferent  fibres  which 
have  strayed  in  the  course  of  development  into  the  wrong  roots,  but  true 
posterior  root-fibres  whose  cells  of  origin  lie  in  the  spinal  ganglia,  and 
which  conduct  efferent  vaso-dilator  impulses  in  the  wrong  direction,  so 
to  speak,  from  the  cord  to  the  periphery — '  antidromic  '  impulses 
(Bayliss). 


i8o  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

Effect  of  Nicotine  on  Nerve-Cells. — A  method  which  has  been  found 
most  fruitful  in  studying  the  relations  of  sympathetic  ganglion-cells  to 
the  vaso-motor  fibres,  as  well  as  to  the  pilo-motor*  and  secretory  fibres 
which  in  certain  situations  are  so  intricately  mingled  with  them,  must 
here  be  mentioned.  It  depends  upon  the  fact  that  when  a  suitable 
dose  of  nicotine  (lo  milligrammes  in  a  cat)  is  injected  into  a  vein,  or  a 
solution  is  painted  on  a  ganglion  with  a  brush,  the  passage  of  nerve- 
impulses  through  the  ganglion  is  blocked  for  a  time  (Langley).  The 
nerve-fibres  peripheral  to  the  ganglion  are  not  affected.  The  question 
whether  efferent  fibres  are  connected  with  nerve-cells  between  a  given 
point  and  their  peripheral  distribution  can,  therefore,  be  answered  by 
observing  whether  any  effect  of  stimulation  is  abolished  by  nicotine. 
If,  for  instance,  the  excitation  of  a  nerve  caused  constriction  of  certain 
bloodvessels  before,  and  has  no  effect  after,  the  application  of  nicotine 
to  a  ganglion,  its  vaso-constrictor  fibres,  or  some  of  them,  must  be  con- 
nected with  nerve-cells  in  that  ganglion.  Langley  has  brought  forward 
e\'idence  that  many  of  the  bodies  which  are  commonly  supposed  to  act 
upon  nerve-endings  (as  nicotine,  curara,  atropine,  pilocarpine,  adrenalin, 
etc.)  really  act  upon  '  receptive  '  substances  of  the  cells  in  connection 
with  which  the  nerve-fibres  end.  These  receptive  substances  are  con- 
ceived to  be  capable  of  being  specifically  affected  by  chemical  bodies 
and  by  nervous  stimuli,  and  in  their  turn  to  be  capable  of  influencing 
the  metabolism  of  the  main  cell  substance  on  which  its  function  depends. 
The  receptive  substances  thus  form  beyond  the  histological  link  of  the 
nerve-ending  a  kind  of  chemical  link  between  the  nerve-fibre  and  the 
cell  which  it  supplies. 

We  have  thus  traced  the  vaso-motor  nerves  from  the  cerebro- 
spinal axis  to  the  bloodvessels  which  they  control;  it  still  remains 
to  define  the  portion  of  the  central  nervous  system  to  which  these 
scattered  threads  are  related,  which  holds  them  in  its  hand  and  acts 
upon  them  as  the  needs  of  the  organism  may  require. 

Vaso-Motor  Centres. — Now,  experiment  has  shown  that  there  is 
one  very  definite  region  of  the  spinal  bulb  which  has  a  most  intimate 
relation  to  the  vaso-motor  nerves.  If  while  the  blood-pressure  in 
the  carotid  is  being  registered,  say,  in  a  curarized  rabbit,  the  central 
end  of  a  peripheral  nerve  like  the  sciatic  is  stimulated,  the  pressure 
rises  so  long  as  the  bulb  is  intact,  this  rise  being  largely  due  to  the 
reflex  constriction  of  the  vessels  in  the  splanchnic  area.  If  a  series 
of  transverse  sections  be  made  through  the  brain,  the  rise  of  pressure 
caused  by  stimulation  of  the  sciatic  is  not  affected  till  the  upper 
limit  of  the  bulb  is  almost  reached.  If  the  slicing  is  still  carried 
downwards,  the  blood-pressure  sinks,  and  the  rise  following  stimu- 
lation of  the  sciatic  becomes  less  and  less.  When  the  medulla  has 
been  cut  away  to  a  certain  level,  only  an  insignificant  rise  or  none 
at  all  can  be  obtained.  The  portion  of  the  medulla  the  removal  of 
which  exerts  an  influence  on  the  blood-pressure,  and  its  increase  by 
reflex  stimulation,  extends  from  a  level  4  to  5  mm.  above  the  point 
of  the  calamus  scriptorius  to  within  i  to  2  mm.  of  the  corpora 
quadrigemina.     Stimulation  of  the  medulla  causes  a  rise,  destruc- 

*  Pilo-motor  nerves  supply  the  smooth  arrecior  pili  muscles,  whose  contrac- 
tion causes  the  hair  to  '  stand  on  end.' 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      i8i 

tion  of  this  portion  of  it  a  severe  fall,  of  general  blood-pressure. 
There  is  evidently  in  this  region  a  nervous  '  centre  '  so  intimately 
related,  if  not  to  all  the  vaso-motor  nerves,  at  least  to  such  very 
important  tracts  as  to  deserve  the  name  of  a  vaso-motor  centre. 
Experiment  has  shown  that  this  is  much  the  most  influential  centre, 
and  it  is  usually  called  the  chief  or  general  vaso-motor  centre.  Some 
writers  prefer  to  speak  of  it  as  the  vaso-constrictor  centre,  since  it 
is  undoubtedly  connected  with  most  or  all  of  the  vaso-constrictor 
paths,  and  has  not  been  shown  to  be  similarly  connected  with  the 
vaso-dilator  paths.  There  is,  indeed,  not  the  same  solid  evadence 
for  the  existence  of  a  general  vaso-dilator  centre  in  the  bulb  as  for 
the  existence  of  the  general  vaso-constrictor  centre.  Yet  there  are 
facts  which  indicate  that  the  bulbar  vaso-motor  centre  or  centres, 
when  reflexly  stimulated,  can,  and  often  do,  respond  not  merely  by 
an  increase  or  a  remission  of  vaso-constrictor  tone,  but  by  a  simul- 
taneous inhibition  of  vaso-constrictor  fibres  and  excitation  of  vaso- 
dilators leading  to  a  fall  of  pressure,  or  by  a  simultaneous  inhibition 
of  vaso-dilators  and  excitation  of  vaso-constrictors  leading  to  a  rise 
of  pressure. 

The  spinal  cells  of  origin  of  the  pre-gangUonic  segments  of  the 
vaso-constrictor  paths  constitute  subordinate  centres  which  either 
normally  support  a  certain  degree  of  vascular  tone,  or  come  to  do  so 
after  the  chief  vaso-motor  centre  has  been  cut  off. 

Thus,  in  the  frog  it  is  possible  to  go  on  destroyfhg  more  and  more 
of  the  cord  from  above  downwards,  and  still  to  obtain  reflex  vaso- 
motor effects,  as  seen  in  the  vessels  of  the  web,  by  stimulating  the 
central  end  of  the  sciatic  nerve.  Although  these  effects  indeed 
diminish  in  amount  as  the  destruction  of  the  cord  proceeds,  yet  a 
distinct  change  can  be  caused  when  only  a  small  portion  of  the  cord 
remains  intact. 

Similarly,  in  the  mammal  evidence  has  been  obtained  of  the 
existence  of  '  centres  '  at  various  levels  of  the  cord,  capable  of  acting 
eventually,  if  not  at  once,  as  vaso-constrictor  centres  after  the  loss 
of  the  controlling  influence  of  the  bulb.  The  best  example  of  a 
vaso-dilator  centre  is  that  situated  in  the  lumbar  cord,  which  controls 
the  erection  of  the  penis.  After  total  section  of  the  cord  at  the  upper 
limit  of  the  lumbar  region,  erection,  which  is  known  to  be  due  to  a 
reflex  dilatation  of  the  arteries  of  the  organ  through  the  nervi  eri- 
gentes,  can  still  be  caused  (in  dogs)  by  mechanical  stimulation  of 
the  glans  penis,  so  long  as  the  afferent  fibres  of  the  reflex  arc  con- 
tained in  the  nerviis  pudendus  are  intact.  Destruction  of  the  lumbar 
cord  abolishes  the  effect.  It  is  impossible  to  avoid  the  conclusion 
that  a  vaso-dilator  or  erection  centre,  which  is  in  relation  on  the 
one  hand  with  the  nervi  erigentes,  and  on  the  other  with  the  ncrvus 
pudendus,  exists  in  the  lower  portion  of  the  spinal  cord.  Vaso- 
motor centres  for  the  hind-limbs  have  also  been  located  in  the 


l82  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

same  region.  When  the  brain,  the  bulb,  and  the  upper  portion  of 
the  cord  have  been  ehminated  by  Ugation  of  all  the  arteries  from 
which  blood  can  possibly  reach  them,  a  sufficient  vascular  pressure 
persists  to  permit  the  circulation  to  go  on  in  the  lower  portion  of 
the  body  for  hours.  And  while  section — or  freezing  (Fig.  80) — of 
the  cord  in  the  lower  cervical  region  causes  a  marked  fall  of  pressure, 
this  is  not  permanent  if  the  animal  is  allowed  to  survive.  Forty-one 
days  after  total  section  of  the  cord  at  the  seventh  cervical  segment 
in  a  dog  an  arterial  pressure  of  130  mm.  of  mercur}^  was  found.  A 
mechanism  for  the  maintenance  of  vascular  tone  exists  even  beyond 
the  limits  of  the  central  nervous  system.  For  when  the  lower 
portion  of  the  cord  is  completely  destroyed,  the  dilatation  of  the 
vessels  of  the  hind-limbs,  which  is  at  first  so  conspicuous,  passes 
away  after  a  time,  the  functions  of  vaso-motor  centres  having 
perhaps  been  assumed  by  the  sympathetic  ganglia  (Goltz  and 
Ewald).     When  the  lumbo-sacral  sympathetic  chain  is  extirpated, 


>xf^^iM{ 


Fig.  80. — Effect  on  Blood- Pressure  of  Freezing  Spinal  Cord  (Pike).  At  i  the  first 
or  second  dorsal  segment  of  a  dog's  cord  was  frozen  with  liquid  air;  at  2  and  3 
central  end  of  sciatic  stimulated  without  effect  on  pressure  (respectively  one  and 
a  half  and  three  minutes  after  freezing  of  cord).     (Four-fifths  of  eriginal  size.) 

there  is  a  further  loss  of  vascular  tone  in  the  affected  region.  But 
even  this  is  not  irremediable.  After  a  time  recovery  again  occurs, 
although  it  may  be  more  partial  and  tardy  than  before.  This  may 
take  place  either  through  the  intervention  of  still  more  peripheral 
ganglia,  or  through  the  development  of  a  certain  tonus  by  the 
muscular  fibres  of  the  vessels  when  abandoned  to  themselves. 

As  to  the  nature  of  the  tone  of  the  general  vaso-motor  centre,  the 
same  question  may  be  asked  which  has  been  already  discussed  for 
the  cardio-inhibitory  centre.  Is  it  reflex,  or  does  it  depend  upon 
direct  excitation  of  the  centre  by  some  constituent  of  the  blood  or 
lymph,  or  some  substance  produced  in  the  centre  itself  ?  The  best 
answer  which  can  at  present  be  made  is  that  a  constant  central 
excitation  by  the  carbon  dioxide  formed  in  the  centre  or  circulating 
in  the  blood  is  a  not  unimportant  factor  in  the  maintenance  of  the 
vaso-motor  tone.  A  marked  diminution  in  the  carbon  dioxide 
tension  of  the  blood,  a  condition  which  is  termed  '  acapnia,'  may 
indeed  contribute  to  the  severe  fall  of  blood-pressure  associated  with 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      183 

surgical  shock  (Henderson).  In  addition  to  the  direct  influence  of 
carbon  dioxide,  and  possibly  of  other  substances,  the  arrival  of 
afferent  impulses  at  the  centre  seems  to  play  a  part  in  maintaining 
that  continual  discharge  of  efferent  impulses  along  the  vaso-motor 
nerves  which  constitutes  its  tone.  In  this  regard,  the  vaso-motor 
centre  occupies  an  intermediate  position  between  the  respiratory 
centre,  the  most  purely  automatic,  and  the  cardio-inhibitorj^  centre, 
the  most  purely  reflex  of  the  three  great  bulbar  mechanisms. 

Of  the  anatomical  relations  of  the  nerve-cells  that  make  up  the 
bulbar  and  spinal  vaso-motor  centres,  little  more  is  known  than  may 
be  deduced  from  the  pliysiological  facts  we  have  been  reciting.  It  has 
been  surmised  on  histological  grounds  that  certain  cells  of  small  size 
scattered  up  and  down  the  thoracic  and  upper  lumbar  regions  of  the 
cord  in  the  lateral  horn  (intcrmedio-lateral  tract),  and  perhaps  cropping 
out  also  in  the  bulb,  arc  vaso-motor  cells.  There  is  good  evidence  that 
the  pre -gang!  ionic  sympathetic  fibres,  including  the  vaso-motor  fibres 
which  we  have  already  discovered  emerging  from  the  cord  in  the  spinal 
roots,  are  connected  with  these  cells.  And,  indeed,  there  is  reason  to 
believe  that  the  connection  is  made  without  the  intervention  of  any 
other  nerve-cells,  and  that  the  axis-cylinders  of  these  vaso-motor  fibres 
are  the  axis-cylinder  processes  of  the  vaso-motor  cells.  So  that  the 
simplest  efferent  path  along  which  vaso-motor  impulses  can  pass  may 
be  considered  as  built  up  of  two  neurons,  one  with  its  cell-body  in  the 
cord,  and  the  other  in  a  sympathetic  ganglion.  Less  is  knowm  of  the 
elements  which  constitute  the  bulbar  centre  and  of  their  connections. 
But  since  it  would  appear  that  the  spinal  vaso-motor  centres  are  under 
the  control  of  the  chief  centre  in  the  bulb,  it  is  necessary  to  suppose 
that  the  axis-cylinder  processes  of  some  of  the  cells  of  the  bulbar  centre 
come  into  relation  with  the  spinal  vaso-motor  cells,  and  that  impulses 
passing,  let  us  say,  ii^om  the  bulb  to  the  vessels  of  the  leg,  would  have 
to  traverse  three  neurons  (p.  823). 

Vaso-Motor  Reflexes. — We  have  already  seen  that  the  cardiac 
centres  are  constantly  influenced  by  afferent  impulses,  and  that  in 
the  direction  either  of  augmentation  or  inhibition.  The  vaso-motor 
centre  in  the  bulb  is  equally  sensitive  to  such  impulses.  They 
reach  it  for  the  most  part  along  the  same  nerves,  and  by  increasing  or 
diminishing  its  tone  cause  sometimes  constriction  and  sometimes 
dilatation  of  the  vessels,  the  result  depending  partly  upon  the  ana- 
tomical connection  of  the  afferent  fibres,  but  apparently  in  part  also 
upon  the  state  of  the  centre. 

Of  the  afferent  nerves  that  cause  vaso-dilatation,  the  most  im- 
portant is  the  depressor,  whose  reflex  inhibitory  action  on  the  heart 
has  been  already  described.  The  fall  in  the  arterial  pressure  is  due 
chiefly,  not  to  the  inhibition  of  the  heart,  but  to  inhibition  of  the 
vaso-constrictor  tone  of  the  bulbar  vaso-motor  centre,  combined 
with  stimulation  of  vaso-dilator  nerves,  and  consequent  general  dila- 
tation of  the  arterioles  throughout  the  body.  That  the  depressor 
action  involves  excitation  of  vaso-dilators  follows  from  the  fact  that 
vaso-dilatation  occurs  in  the  limbs  on  stimulation  of  the  depressoi 
after  their  vaso-constrictor  nerves  have  been  cut.     Stimulation  of 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


the  depressor  produces  its  usual  result  after  section  of  the  vagi.  It 
has  been  suggested  that  the  function  of  the  nerve  is  to  act  as  an 
automatic  check  upon  the  blood-pressure  in  the  interest  both  of  the 
heart  and  the  vessels,  its  terminations  in  the  aorta  or  the  ventricular 
wall  being  mechanically  stimulated  when  the  pressure  tends  to  rise 
towards  the  danger  limit.  In  rare  cases,  efferent  inhibitory  fibres 
for  the  heart  have  been  found  in  the  depressor  of  the  rabbit. 

Many  of  the  peripheral  nerves  contain  fibres  whose  stimulation 
is  followed  by  dilatation  of  the  bloodvessels  in  special  regions, 


Fig.  8i. — Diagram  of  De- 
pressor Nerve  in  Rabbit. 
X,  vagus;  SL,  superior 
laryngeal  branch  of  vagus; 
D,  depressor  fibres.  The 
arrows  show  the  course  of 
the  impulses  that  affect 
the  blood-pressure. 


Fig.  82. — Blood -Pressure  Tracing:  Rabbit.  Central 
end  of  depressor  stimulated  at  i;  stimulation 
stopped  at  2.     Time-trace,  seconds. 


usually  the  areas  to  which  they  are  themselves  distributed,  accom- 
panied by  constriction  of  distant  and,  it  may  be,  more  extensive 
vascular  tracts.  Thus,  the  usual  local  effect  of  stimulating  the 
afferent  fibres  of  the  lowest  three  thoracic  nerves,  in  whose  anterior 
roots  run  the  vaso-motor  fibres  for  the  kidney,  is  a  dilatation  of  the 
renal  vessels  (Bradford),  and  the  usual  local  effect  of  stimulating 
the  infra-orbital  or  supra-orbital  nerve  a  dilatation  of  the  external 
maxillary  artery.  But  the  general  effect  in  both  cases  is  vaso- 
constriction in  other  regions  of  the  body,  which  more  than  com- 
pensates the  local  dilatation,  so  that  the  arterial  blood-pressure 
rises.  It  is  not  difficult  to  see  that  both  of  these  changes  render  it 
easier  for  the  part  to  obtain  an  increased  supply  of  blood. 

Sometimes  the  reciprocal  relation  between  vaso-dilatation  in  one  part 
of  the  body  and  vaso-constriction  in  another  is  only  apparent.  For 
example,  stimulation  of  the  cut  end  of  the  sciatic  causes,  as  we  have 
already  seen,  extensive  vaso-constriction  and  a  notable  rise  in  the  blood- 
pressure.     The  constriction  certainly  involves  the  splanchnic  area;  but 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      185 

superficial  parts,  as  the  lips,  may  be  seen  to  be  flushed  with  blood. 
In  asphyxia,  when  the  vaso-motor  centres  are  directly  stimulated  by 
the  venous  blood,  this  apparent  antagonism  is  still  better  marked:  the 
cutaneous  vessels  are  widely  dilated  and  engorged,  the  face  is  livid, 
but  the  abdominal  organs  are  pale  and  bloodless  (Heidenhain).  The 
blood-pressure  rises  rapidly,  reaches  a  maximum,  and  then  gradually 
falls  as  the  vaso-motor  centre  becomes  paralyzed  (Figs.  84  and  85).  It 
has  been  shown  that  in  both  cases  vaso-constriction  01  the  skin  is  really 
produced  as  well  as  vaso-constriction  of  the  internal  organs,  but  the 
increased  blood-pressure  mechanically  overcomes  the  constriction  of 
the  cutaneous  vessels. 

The  kind  of  stimulus  seems  to  have  something  to  do  with  the 
direction  of  the  reflex  vaso-motor  change.  For  while  electrical 
stimulation  of  every  muscular  nerve,  even  of  the  very  finest  twigs 
that  can  be  isolated  and  laid  on  electrodes,  provokes  always,  whether 
the  shocks  follow  each  other  rapidly  or  slowly,  a  rise  of  c^eneral 


Fig.  83. — Pressor  Effect  of  Stimulation  of  Central  End  of  Vagus  in  a  Cat  during 
Resuscitation  after  Cerebral  Anamia.  The  depressions  in  the  signal  line  ABC 
indicate  the  duration  of  three  successive  excitations  of  equal  strength,  sixty-five, 
seventy-three,  and  seventy-nine  minutes  respectively  after  restoration  of  the 
circulation.  The  pressor  effect  increases  as  resuscitation  proceeds.  Later  on 
the  original  depressor  effect  was  again  obtained.  The  upper  tracing  is  that  of 
the  artificial  respiration.     (Two-thirds  original  size.) 

blood-pressure,  mechanical  stimulation  of  a  muscle,  as  by  kneading 
or  massage,  causes  a  fall.  The  condition  of  the  afferent  fibres  also 
exerts  an  influence.  For  example,  excitation  of  the  central  end  of  a 
sciatic  nerve  that  has  been  cooled  is  followed  by  vaso- dilatation 
and  fall  of  pressure,  the  opposite  of  the  ordinary  result.  These  and 
similar  facts  have  led  to  the  idea  that  most  afferent  nerves  contain 
two  kinds  of  fibres,  whose  stimulation  can  affect  the  activity  of  the 
vaso-motor  centres — '  reflex  vaso-constrictor,'  or  '  pressor  '  fibres, 
and  '  reflex  vaso-dilator,'  or  '  depressor  '  fibres.  The  branch  of  the 
vagus,  however,  to  which  the  name  '  depressor '  has  been  specially 
given  is  usually  described  as  the  only  peripheral  nerve  the  excitation 
of  which  is  in  all  circumstances  followed  by  a  general  diminution  of 
arterial  pressure.  But  this  is  not  strictlv  correct,  for  at  an  early 
period  in  the  resuscitation  of  the  brain  after  anaemia  excitation  of 


1 86  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

the  rabbit's  '  depressor  '  causes  a  slight  rise  of  pressure  not  followed 
by  any  fall.  This,  perhaps,  indicates  the  presence  in  the  '  depressor  ' 
of  a  small  number  of  pressor  fibres,  which  are  resuscitated  sooner 
than  the  depressor  fibres  proper.  The  same  phenomenon,  only 
more  marked,  may  be  seen  when  the  central  end  of  the  cat's  vagus, 
containing  the  depressor  fibres,  is  excited  at  intervals  during  resus- 
citation (Fig.  83).  Or  the  result  may  depend  upon  a  change  in  the 
response  of  the  altered  vaso-motor  centres  to  impulses  reaching 
them  along  the  depressor  fibres.  If  specific  '  depressor  '  fibres  exist 
in  other  nerves,  they  are  so  mingled  with  '  pressor  '  fibres  that  their 
action  is  masked  when  both  are  stimulated  together.  The  state  of 
the  vaso-motor  centre  is  unquestionably  a  factor  which  has  some 
importance  in  determining  the  result  of  reflex  vaso-motor  stimula- 
tion. For  instance,  in  an  animal  deeply  anaesthetized  with  chloro- 
form or  chloral,  excitation  of  pressor  fibres  (in  an  ordinary  sensory 


Fig.  84. — Rise  of  Blood- Pressure  in  Asphyxia  :  Rabbit.  Respiration  stopped  at  i. 
Interval  between  2  and  3  (not  reproduced)  44  seconds,  during  which  the  blood- 
pressure  steadily  rose.     At  4,  respiration  resumed.     Time-trace,  seconds. 

nerve)  causes,  not  a  rise,  but  a  fall  of  blood -pressure;  while  in  an 
animal  fully  under  the  influence  of  strychnine  stimulation  of  the 
depressor  nerve  causes  not  a  fall,  but  a  rise. 

The  vaso-motor  reflexes  in  man  can  be  conveniently  studied  by 
the  calorimetric  method  described  on  p.  220.  One  of  the  most 
important  of  the  vaso-motor  reactions  is  that  by  which  the  vessels 
of  the  skin  respond  to  the  temperature  of  the  environment  so  as 
to  regulate  the  loss  of  heat  from  the  body  (p.  674).  When  one 
hand,  e.g.  the  left,  is  immersed  in  cold  water  (say  at  about  8°  C), 
the  blood-flow  in  the  right  is  at  once  reduced  owing  to  reflex  vaso- 
constriction. Other  parts  of  the  body  are  also  affected,  but  not  so 
readily  as  the  contra-lateral  hand,  since  the  segments  of  the  cord 
into  which  the  afferent  fibres  from  a  given  skin  area  run  are  at  the 
same  time  the  segments  from  which  the  efferent  vaso-motor  fibres 
for  the  symmetrically-placed  area  on  the  opposite  side  of  the  body 
arise.     The  reflex  diminution  in  the  flow  persists  for  a  time  which 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      187 


varies  with  the  individual,  the  external  temperature,  and  other 
circumstances,  and  then  as  a  rule  rather  suddenly  the  vaso-con- 
striction  gives  way  and  the  flow  begins  again  to  increase,  even  while 
the  left  hand  is  still  kept  in  the  cold  water.  When  the  left  hand  is 
transferred  from  the  cold  to  warm  water  (at  43°  or  44°  C),  the  fitst 
effect  is  a  transient  diminution  in  the  blood-flow  in  the  right  hand. 
This  soon  gives  place  to  an  increase  (vaso-dilatation).  As  an  ex- 
ample, the  following  table  gives  the  condensed  results  of  three 
experiments  on  two  young  men.  Experiments  II.  and  III.  were  on 
the  same  man  at  an  interval  of  three  days. 


Temperature  of — 

Duration 

Flow  in  Grms. 

Experi- 
ment. 

of 
Observation 

per  100  c.c. 
of  Rislit  Hand 

Left  Hand  in — 

Arterial 
Hlood. 

Room. 

Calorim. 

in  Minutes. 

per  Minute. 

'28-9' 
29-0 

r3i-i 

16 

I2'2 

I. 

36-6  lli;:i 

4 

6-9 

Cold  water. 

29-0 
.29'I. 

6 

9-9 

Cold  water  still. 

132-3 

II 

II-6 

Warm  water. 

'24-0' 

'30-9 

13 

lO-I 



24-2 

31-3 

13 

5-0 

Cold  water. 

II. 

■   23-9  • 

36-0 

■ 

31-4 

2 

3-4 

Warm  water. 

23-9 

31-5 

3 

8-4 

Warm  water  still. 

123-9; 

I31-7 

7 

15-0 

Warm  water  still. 

'24-8' 

[31-6 

15 

12-4 

— 

24-4 

32-1 

5 

5-9 

Cold  water. 

111. 

24-4   ■ 

36-5 

- 

32-2 

5 

10-7 

Cold  water  still. 

24-4 

3^-4 

3 

7-9 

Warm  water. 

124-5; 

132-6 

7 

17-6 

Warm  water  stiU. 

Such  facts  enable  us  to  some  extent  to  understand  the  manner  in 
which  the  distribution  of  the  blood  is  adjusted  to  the  requirements 
of  the  different  parts  of  the  body,  so  that  to  a  certain  degree  of 
approximation  no  organ  has  too  much,  and  none  too  little.  The 
blood-supply  of  the  organs  is  always  shifting  with  the  calls  upon 
them.  Now,  it  is  the  actively-digesting  stomach  and  the  actively- 
secreting  glands  of  the  ahmentary  tract  which  must  be  fed  with  a 
full  stream  of  blood,  to  supply  waste  and  to  carry  away  absorbed 
nutriment.  Again,  it  is  the  working  muscles  of  the  legs  or  of  the 
arms  that  need  the  chief  blood-supply.  But  wherever  the  call  may 
be,  the  vaso-motor  mechanism  is  able,  in  health,  to  answer  it  by 
bringing  about  a  widening  of  the  small  arteries  of  the  part  which 
needs  more  blood,  and  a  compensatory  narrowing  of  the  vessels 
of  other  parts  whose  needs  are  not  so  great. 

It  is  also  through  the  vaso-motor  system,  and  especially  by  the 
action  of  that  portion  of  it  which  governs  the  abdominal  vessels,  and 


1 88  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

of  the  nerves  that  regulate  the  work  of  the  heart,  that  in  animals 
to  which  the  upright  position  is  normal  (monkey)  and  in  man  the 
influence  of  changes  of  posture  on  the  circulation  is  almost  com- 
pletely compensated.*  The  pressure  in  the  upper  part  of  the 
huftian  brachial  artery  has  been  measured  with  a  sphygmoman- 
ometer, first  in  the  horizontal  and  then  immediately  afterwards  in 
the  standing  posture,  and  in  health  it  has  been  found  to  remain 
practically  unchanged  (Hill).  But  if  the  person  was  overworked  or 
out  of  sorts,  the  compensation  was  less  complete.  It  is  well  known 
that  in  debilitated  persons,  especially  if  long  confined  to  bed,  the 
sudden  assumption  of  the  upright  position  may  cause  vertigo,  and 
even  syncope,  the  normal  compensatory  mechanism  being  deranged. 
In  such  animals  as  the  rabbit  this  compensation  is  totally  inefficient. 
When  a  domesticated  rabbit,  which  has  been  kept  in  a  hutch,  is 
suspended  vertically  with  the  feet  down,  the  blood  drains  into  the 
abdominal  vessels,  syncope  speedily  ensues,  and  in  a  period  that 
ranges  from  less  than  a  quarter  to  three-quarters  of  an  hour  the 
animal  dies  in  the  convulsions  of  acute  cerebral  anaemia  (Salathe, 
Hill).  The  head-down  position  has  no  ill-effects.  In  wild  rabbits, 
whose  abdominal  wall  is  more  tense  and  elastic,  these  fatal  symp- 
toms are  not  easily  produced,  and  the  same  is  true  of  cats  and  dogs. 
But  in  all  animals,  when  the  compensation  is  destroyed,  as  in 
paralysis  of  the  vaso-motor  centre  by  chloroform,  the  circulation 
may  be  profoundly  influenced  by  the  position  of  the  body:  elevation 
of  the  head  may  lead  to  cerebral  anaemia,  syncope,  and  even  death ; 
elevation  of  the  legs,  and  particularly  the  abdomen,  may  restore  the 
sinking  pulse  by  filling  the  heart  and  the  vessels  of  the  brain.  If  a 
chloralized  dog  be  fastened  on  a  board  which  can  be  rotated  about 
a  horizontal  axis  passing  under  the  neck,  the  blood-pressure  in  the 
carotid  artery  falls  greatly  when  the  animal  is  made  to  assume  the 
vertical  position  with  the  head  up,  and  either  rises  a  little  or  remains 
practically  unchanged  when  the  head  is  made  to  hang  down.  So 
great  may  the  fall  of  pressure  be  in  the  former  position  that  death 
may  occur  if  it  be  long  maintained  (Practical  Exercises,  p.  212). 

*  Two  factors  may  be  distinguished  in  the  blood-pressure,  the  hydrostatic 
and  the  hydrodynamic  elements.  The  hydrostatic  portion  of  the  pressure  is 
due  to  the  weight  of  the  column  of  blood  acting  on  the  vessel;  the  hydro- 
dynamic  portion  of  the  pressure  is  due  to  the  work  of  the  heart.  If  a  dog  be 
securely  fastened  to  a  holder  arranged  in  such  a  way  that  the  animal  can  be 
placed  vertically,  with  the  head  up  or  down,  and  the  mean  blood-pressure  in 
the  crural  artery  be  measured  in  the  two  positions,  there  will  be  a  considerable 
difference.  I'^or  when  the  legs  are  uppermost  the  heart  has  to  overcome  the 
weight  of  the  column  of  blood  rising  above  it  to  the  crural  artery;  when  the 
head  is  uppermost  the  action  of  the  heart  is  reinforced  by  the  weight  of  the 
blood.  And  if  no  change  were  produced  in  the  action  of  the  heart,  or  in  the 
general  resistance  of  the  vascular  path,  by  the  change  of  position,  this  differ- 
ence would  be  equal  to  the  pressure  of  a  column  of  blood  twice  as  high  as  the 
straight-line  distance  between  the  cannula  and  the  point  of  the  arterial  system 
at  which  the  pressure  is  the  same  with  head  up  as  with  head  down  (indifferent 
point). 


THE  NERVOUS  REGULATION  OF  THE  BLOODVESSELS      li 


Finally,  it  is  in  virtue  of  the  amazing  power  of  accommodation 
possessed  by  the  vascular  system,  as  controlled  by  the  vaso- motor 
and  cardiac  nerves,  that  so  long  as  these  are  not  disabled  the  total 
quantity  of  blood  may  be  greatly  diminished  or  greatly  increased, 
without  endangering  life,  or  even  causing  more  than  a  transient 
alteration  in  the  arterial  pressure.  It  is  not  until  at  least  a  quarter 
of  the  blood  has  been  withdrawn  that  there  is  any  notable  effect 
on  the  pressure,  for  the  loss  is  quickly  compensated  by  an  increase 
in  the  activity  of  the  heart  and  a  constriction  of  the  small  arteries. 
An  animal  may  recover  after  losing  considerably  more  than  half-its 
blood.*  Conversely,  the  volume  of  the  circulating  hquid  may  be 
doubled  by  the  injection  of  blood  or  physiological  salt  solution 
without  causing  death,  and  increased  by  50  per  cent,  without  any 
marked  increase  in  the  pressure.     The  excess  is  promptly  stowed 


mM 


^  ^jt 


' '  ■ ' ' ' ' « ' ' ' ' ' '  i '  ■ "  I '  ■ ' ' ' ' "  ■  ■ "  1 1 '  ■  ■  1 1 1 1 1 1 1 

Fig.  85. — Blood- Pressure  Tracing  from  a  Dog  poisoned  with  Alcohol. 
The  respiratory  centre  being  paralyzed,  respiration  stopped,  and 
the  t>^)ical  rise  of  blood-pressure  in  asphyxia  took  place.  The 
pressure  had  again  fallen,  and  total  paralysis  of  the  vaso-motor 
centre  was  near  at  hand,  when  at  A  the  animal  made  a  single 
respiratory  movement.  The  quantity  of  oxygen  thus  taken  in  was  enough 
to  restore  the  vaso-motor  centre,  and  the  blood-pressure  again  rose.  This 
was  repeated  five  or  six  times.     (Three-fourths  original  size.) 

away  in  the  dilated  vessels,  especially  those  of  the  splanchnic  area; 
the  water  passes  rapidly  into  the  lymph,  and  is  then  more  gradually 
eliminated  by  the  kidneys. 

From  these  facts  we  can  deduce  the  practical  lesson,  that  blood- 
letting, unless  fairly  copious,  is  useless  as  a  means  of  lowering  the 
general  arterial  pressure,  while  it  need  not  be  feared  that  transfusion 
of  a  considerable  quantity  of  blood,  or  of  salt  solution,  in  cases  of 
severe  haemorrhage  will  dangerously  increase  the  pressure.  And 
from  the  physiological  point  of  view  the  term  '  haemorrhage '  includes 
more  than  it  does  in  its  ordinary  sense.  For  as  dirt  to  the  sani- 
tarian is  '  matter  in  the  wrong  place,'  haemorrhage  to  the  physiolo- 
gist is  blood  in  the  wrong  place.     Not  a  drop  of  blood  may  be  lost 

*  It  is  not  usually  possible  to  obtain  quite  two-thirds  of  the  total  blood  by 
bleeding  a  dog  from  a  large  artery.  In  seven  dogs  bled  from  the  carotid, 
the  ratio  of  the  weight  of  the  blood  obtained  to  the  body-weight  was 
I  :  24-7,  I  :  2i'7,  I  :  20-7,  i  :  20-6,  i  :  i8'6,  i  :  16,  i  :  I3'3  In  the  last  case, 
the  blood  clotted  with  abnormal  slowness,  and  the  animal  died  in  a  few 
minutes. 


190  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

from  the  body,  and  yet  death  may  occur  from  haemorrhage  into  the 
pleural  or  the  abdominal  cavity,  into  the  stomach  or  intestines. 
Not  only  so,  but  a  man  may  bleed  to  death  into  his  own  blood- 
vessels; in  surgical  shock,  it  would  appear  that  the  blood  which  ought 
to  be  circulating  through  the  brain,  heart  and  lungs  may  stagnate 
in  the  dilated  veins. 


Section  VII. — The  Lymphatic  Circulation. 

As  has  already  been  stated,  some  of  the  constituents  of  the  blood, 
instead  of  passing  back  to  the  heart  from  the  capillaries  along  the  veins, 
find  their  way  by  a  much  more  tedious  route  along  the  lymphatics. 
The  blood  capillaries  are  everywhere  in  very  intimate  relation  with 
lymph  capillaries,  which,  completely  lined  with  epithelioid  cells,  lie  in 
irregular  spaces  in  the  connective-tissue  that  everywhere  accompanies 
and  supports  the  bloodvessels.  The  constituents  of  the  blood-plasma 
are  filtered  through,  or  secreted  by  the  capillary  walls  into  these  lymph 
spaces,  and  mingling  there  with  waste  products  discharged  by  the  cells 
of  the  tissues,  form  the  liquid  known  as  tissue  liquid  or  tissue  lymph. 
From  the  tissue  liquid  the  lymph  capillaries  take  up  the  constituents 
of  the  '  lymphatic  '  lymph,  which  then  passes  into  larger  lynjphatic 
vessels,  with  lymphatic  glands  at  intervals  on  their  course.  These  fall 
into  still  larger  trunks,  and  finally  the  greater  part  of  the  lymph  reaches 
the  blood  again  by  the  thoracic  duct,  which  opens  into  the  venous 
system  at  the  junction  of  the  left  subclavian  and  internal  jugular  veins. 
The  lymph  from  the  right  side  of  the  head  and  neck,  the  right  extremity, 
and  the  right  side  of  the  thorax,  with  its  viscera,  is  collected  by  the 
right  lymphatic  duct,  which  opens  at  the  junction  of  the  right  sub- 
clavian and  internal  jugular  veins.  The  openings  of  both  ducts  are 
guarded  by  semilunar  valves,  which  prevent  the  reflux  of  blood  from 
the  veins.  Serous  cavities  like  the  pleural  sacs,  although  differing 
from  ordinary  lymph  spaces,  are  connected  through  small  openings, 
called  stomata,  with  lymphatic  vessels. 

The  rate  of  flow  of  the  lymph  in  the  thoracic  duct  is  very  small  com- 
pared with  that  of  the  blood  in  the  arteries— only  about  4  mm.  per 
second,  according  to  one  observer.  Nevertheless,  a  substance  injected 
into  the  blood  can  be  detected  in  the  lymph  of  the  duct  in  four  to  seven 
minutes  (Tschirwinsky) .  The  factors  which  contribute  to  the  main- 
tenance of  the  lymph  flow  are : 

(i)  The  pressure  under  which  it  passes  from  the  blood  capillaries  into 
the  lymph  spaces  and  from  the  lymph  spaces  into  the  lymph  capillaries. 
The  pressure  in  the  thoracic  duct  of  a  horse  may  be  as  high  as  12  mm. 
of  mercury;  in  the  dog  it  may  be  less  than  i  mm.  The  difference  is 
probably  due,  in  part  at  least,  to  a  difference  in  the  experimental  con- 
ditions, dogs  being  usually  auccsthetized  for  such  measurements,  horses 
not.  The  pressure  in  the  lymph  capillaries  must,  of  course,  be  higher 
than  in  the  thoracic  duct — how  much  higher  we  do  not  know. 

(2)  The  contraction  of  muscles  increases  the  pressure  of  the  lymph 
by  compressing  the  channels  in  which  it  is  contained,  and  the  valves, 
with  which  the  lymphatics  arc  even  more  richly  provided  than  the 
veins,  hinder  a  backward  and  favour  an  onward  flow.  The  contractions 
of  the  intestines,  and  especially  of  the  villi,  aid  the  inovement  of 
the  chyle.  By  the  contraction  of  the  diaphragm,  substances  may 
be  sucked  from  the  peritoneal  cavity  into  the  lymphatics  of  its 
central  tendon,  through  the  stomata  m  tiie  serous  layer  with  which 


THE  LYMPHATIC  CIRCULATION  191 

iLs  lower  surface  is  clad.  It  is  even  possible  by  passive  movements  of 
the  diaphragm  in  a  dead  rabbit  to  inject  its  lymphatics  with  a  coloured 
liquid  placed  on  its  peritoneal  surface.  Passive  movements  of  the 
limbs  and  massage  of  the  muscles  are  also  known  to  hasten  the  sluggish 
current  of  the  lymph,  and  are  sometimes  employed  with  this  object  in 
the  treatment  of  disease. 

(3)  The  movements  of  respiration  aid  the  flow.  At  every  inspiration 
the  pressure  in  the  great  veins  near  the  heart  becomes  negative,  and 
lymph  is  sucked  into  them  (p.  225). 

(4)  In  some  animals  rhythmically -contracting  muscular  sacs  or 
hearts  exist  on  the  course  of  the  lymphatic  circulation.  The  frog  has 
two  pairs,  an  anterior  and  a  posterior,  of  these  lymph  hearts,  which 
pulsate,  although  not  with  any  great  regularity,  at  an  average  rate  of 
sixty  to  seventy  beats  a  minute,  and  are  governed  by  motor  and  inhibi- 
tory centres  situated  in  the  spinal  cord.  The  beat  is  not  directly  ini- 
tiated from  the  cord,  but  the  tonic  influence  of  the  cord  is  necessary  in 
order  that  the  lymph  hearts  may  continue  to  beat  (Tschermak).  Such 
hearts  are  also  found  in  reptiles.  It  is  possible  that  in  animals  without 
localized  lymph  hearts  the  smooth  muscle,  which  is  so  conspicuous  an 
element  in,  the  walls  of  the  lymphatic  vessels,  may  aid  the  flow  by 
rhythmical  ■  contractions . 

PRACTICAL  EXERCISES  ON  CHAPTER  III. 

1.  Microscopic  Examination  of  the  Circulating  Blood. — (i)  Take  a 
tadpole  and  lay  it  on  a  glass  slide.  Cover  the  tail  with  a  large  cover- 
slip,  and  examine  it  wdth  the  low  power  (Leitz,  oc.  III.,  obj.  3). 
Generally  the  tail  will  stick  so  closely  to  the  slide,  and  the  animal  will 
move  so  little,  that  a  sufficiently  good  view  of  the  circulation  can  be 
obtained.  If  there  is  any  trouble,  destroy  the  brain  with  a  needle. 
Observe  the  current  of  the  blood  in  the  arteries,  capillaries  and  veins. 
An  artery  may  be  easily  distinguished  from  a  vein  by  looking  for  a 
place  at  which  the  \-essel  bifurcates.  In  veins  the  blood  flows  in  the 
two  branches  of  the  fork  towards  the  point  of  bifurcation,  in  arteries 
away  from  it.     Sketch  a  part  of  a  field. 

To  Pith  a  Frog. — Wrap  the  animal  in  a  towel,  bend  the  head  for\vards 
with  the  index-finger  of  one  hand,  feel  with  the  other  for  the  depression 
at  the  junction  of  the  head  and  backbone,  and  push  a  narrow-bladed 
knife  right  down  in  the  middle  line.  The  spinal  cord  will  thus  be 
divided  with  little  bleeding.  Now  push  into  the  cavity  of  the  skull  a 
piece  of  pointed  lucifer  match.  The  brain  will  thus  be  destroyed.  The 
spinal  cord  can  be  destroyed  by  passing  a  blunt  needle  dowTi  inside  the 
vertebral  canal. 

(2)  Take  a  frog  and  pith  its  brain  only,  inserting  a  match  to  prevent 
bleeding.  Pin  the  frog  on  a  plate  of  cork  into  one  end  of  which  a 
glass  slide  has  been  fastened  with  sealing-wax.  Lay  the  web  of  one 
of  the  hind-legs  on  the  glass  and  gently  separate  two  of  the  toes,  if 
necessary  by  threads  attached  to  them  and  secured  to  the  cork  plate. 
Put  the  plate  on  the  microscope-stage  and  fasten  by  the  clips  (sec 
pp.  13,  iiS). 

(3)  After  the  normal  circulation  has  been  studied  thoroughly  put  a 
very  small  drop  of  tincture  of  cantharidcs  on  the  portion  of  the  web 
which  is  in  the  field  of  the  microscope,  using  a  fine  pipette.  Observe 
the  process  o*f  infiammatiou,  including  stasis  and  diapedesis  (p.  61). 

2.  Anatomy  of  the  Frog's  Heart. — Expose  the  heart  of  a  pithed  frog 
by  pinching  up  the  skin  over  the  abdomen  in  the  middle  lino,  dividing 
it  with  scissors  up  to  the  lower  jaw,  and  then  cutting  through  the 


192 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


abdominal  muscles  and  the  bony  pectoral  girdle.  The  external  ab- 
dominal vein,  which  will  be  observed  on  reflecting  the  skin,  can  be 
easily  avoided.  The  heart  will  now  be  seen  enclosed  in  a  thin  mem- 
brane, the  pericardium,  which  shpuld  be  grasped  with  fine-pointed 
forceps  and  freely  divided.  Connecting  the  posterior  surface  of  the 
heart  and  the  pericardium  is  a  slender  band  of  connective  tissue,  the 
fraenum.  A  silk  ligature  may  be  passed  around  this  with  a  threaded 
curved  needle,  or  curved  fine-pointed  forceps,  and  tied,  and  then  the 
fraenum  may  be  divided  posterior  to  the  ligature.  The  anatomical 
arrangement  of  the  various  parts  of  the  heart  should  now  be  studied. 
Note  the  single  ventricle  with  the  bulbus  arteriosus,  the  two  auricles, 
and  the  sinus  venosus,  turning  the  heart  over  to  see  the  latter  by  means 
of  the  ligature.  Observe  the  whitish  crescent  at  the  junction  of  the 
sinus  venosus  and  the  right  auricle  (Fig.  86). 

3.  The  Beat  of  the  Heart. — Note  that  the  auricles  beat  first,  and 
then  the  ventricle.     The  ventricle  becomes  smaller  and  paler  during 

its  systole,  and  blushes 
red  during  diastole. 
Count  the  number  of 
beats  of  the  heart  in  a 
minute.  Now  excise  the 
heart,  lifting  it  by  means 
of  the  ligature,  and  tak- 
ing care  to  cut  wide  of 
the  sinus  venosus.  Place 
the  heart  in  a  small  por- 
celain capsule  on  a  little 
blotting  -  paper  rnoist- 
ened  with  physiological 
salt  solution.*  Observe 
that  it  goes  on  beating. 
Put  a  little  ice  or  snow 
in  contact  with  the  heart, 
and  count  the  number  of 
beats  in  a  minute.  The 
rate  is  greatly  dimin- 
ished. Now  remove  the 
ice  and  blotting-paper,  cover  the  heart  with  the  salt  solution,  and  heat, 
noting  the  temperature  with  a  thermometer.  Observe  that  the  heart 
beats  faster  and  faster  as  the  temperature  rises.  At  40°  to  43°  C. 
it  stops  beating  in  diastole  (heat  standstill).  Now  at  once  pour  off  the 
heated  liquid,  and  run  in  some  cold  salt  solution.  The  heart  will  begin 
to  beat  again. 

4.  Cut  off  the  apex  of  the  ventricle  a  little  below  the  auriculo- 
ventricular  groove.  The  auricles,  with  the  attached  portions  of  the 
ventricle,  go  on  beating.  The  apex  does  not  contract  spontaneously, 
but  can  be  made  to  beat  by  stimulating  it  mechanically  (by  pricking 
it  with  a  needle)  or  electrically.  Divide  the  still  contracting  portion 
of  the  heart  by  a  longitudinal  incision.     The  two  halves  go  on  beating. 

5.  Heart  Tracings. — (i)  Fasten  a  myograph-plate  (Fig.  87)  on  a 
stand.  Take  a  long  light  lever  consisting  of  a  straw  or  a  piece  of 
thin  chip,  armed  at  one  end  with  a  writing-point  of  parchment-paper, 
supported  near  the  other  end  by  a  horizontal  axis,  and  pierced  not 
far  from  the  axis  by  a  needle  carrying  on  its  point  a  small  piece  of 
cork  or  a  ball  of  sealing-wax. 

*  For  frog's  tissues  this  should  be  0-7  to  0*75  per  cent,  sodium  chloride 
solution,  for  mammalian  tissues  a  little  stronger  (about  eg  per  cent.). 


Fig.  86. — Frog's  Heart  with  Stannius'  Ligatures  in 
Position  (Cyon).  Anterior  surface  of  heart  shown 
on  the  left,  posterior  surface  on  the  right,  a,  right 
auricle;  b,  left  auricle;  c,  ventricle;  d,  bulbus  arte- 
riosus ;  e,  f,  aortae ;  g,  sinus  venosus. 


PRACTICAL  EXERCISES 


193 


■^--^^ 


Fig. 


87. — Arrangement  for  obtaining  a 
Heart  Tracing  from  a  Frog. 


A  counterpoise  is  adjusted  on  the  short  arm  of  the  lever  m  the  form 
of  a  small  leaden  weight.  Cover  a  drum  with  glazed  paper  and  smoke 
it.  The  paper  must  be  put  on  so  tightly  that  it  will  not  slip.  To 
smoke  the  drum,  hold  it  by  the  spindle  in  both  hands  over  a  fish-tail 
burner,  depress  the  drum  in  the 
flame,  and  rotate  rapidly.  Avoid 
putting  on  a  heavy  coating  of 
smoke,  as  a  more  delicate  tracing 
is  obtained  when  the  paper  is 
lightly  smoked.  The  speed  of  the 
drum  can  be  varied  by  putting 
in  or  taking  out  a  small  vane. 
Arrange  an  electro-magnetic  time- 
marker  for  writing  seconds  (Fig. 
88).  Pith  a  frog  (bram  only), 
expose  the  heart,  and  put  under 
it  a  cover-slip  to  give  it  support. 
Pin  the  frog  on  the  myograph- 
plate,  and  adjust  the  foot  of  the 
lever  so  that  it  rests  on  the  ven- 
tricle or  the  auriculo- ventricular 
j  tmction .  Bring  the  writing-point 
of  the  lever  and  that  of  the  time- 
marker  vertically  under  each  other  on  the  surfa.ce  of  the  drum.  Set  off 
the  drum  at  the  slow  speed  (say,  a  centimetre  a  second).  When  the 
lever  rests  on  the  auriculo-ventricular  junction,  the  part  of  the  tracmg 
corresponding  to  the  contraction  of  the  heart  will  be  broken  mto  two 

portions,  representing 
the  systole  of  the  auri- 
cles and  ventricle  re- 
spectively. Cut  the 
paper  off  the  drum 
with  a  knife  (keeping 
the  back  of  the  knife 
to  the  drum  to  a^•oid 
>coring  it)  and  carry 
it  to  the  vamishing- 
trough,  holding  the 
tracing  by  the  ends 
with  both  hands, 
smoked  side  up.  Im- 
merse the  middle  of  it 
in  the  varnish,  draw 
first  one  end  and  then 
the  other  through  the 
varnish,  let  it  drip 
for  a  minute  into  the 
trough,  and  fasten  it 
up  with  a  pin  to  dry. 

(2)  Heart  Tracing, 
li'ith  Simultaneous  Re- 
cord of  A  uricular  and  Ventricular  Contractions. — [a)  For  this  purpose  tAvo 
levers  may  l)e  arranged,  one  resting  on  the  auricle,  the  other  on  the  ven- 
tricle, the  writing- points  being  placed  in  the  same  vertical  straight  line 
on  the  drum.     A  convenient  fonn  of  apparatus  is  shown  in  Fig.  89. 

ip)  GaskelVs   Method  {a  modification  of). — Attach  a  silk  ligature  to 
the  v.rj'  apex  of  the   ventricle.     Divide  the   fra^num,  cut  the  aorta 

13 


Fig.  88. — Electro  -  Magnetic  Time  -  .Marker  connected 
with  Metronome.  The  penduhmi  of  the  metro- 
nome carries  a  wire  which  closes  the  circuit  when 
it  dips  into  either  of  the  mercury  cups,  Hg. 


194 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


across  close  to  the  bulbus,  pinch  up  a  tiny  portion  of  the  auricle  and 
ligature  it.  Remove  the  intestines,  liver,  lungs,  etc.,  care  being  taken 
in  cutting  away  the  liver  not  to  injure  the  sinus.  Then  remove  the 
lower  jaw,  and  cut  away  the  whole  of  the  body  except  the  head,  part 
of  the  oesophagus,  and  the  tissue  connecting  it  with  the  heart.  Fix 
the  head  in  a  clamp  sliding  on  an  ordinary  stand.  The  heart  is  held 
at  the  auriculo-ventricular  junction  in  a  Gaskell's  clamp  supported  on 
a  separate  stand.  The  thread  connected  with  the  ventricle  is  brought 
round  a  pulley  and  attached  to  a  lever  above  the  heart.  The  auricle 
is  connected  with  another  lever.  The  writing-points  of  the  two  levers 
are  arranged  in  a  vertical  line  on  the  drum.  The  small  pulley  must 
be  oiled  from  time  to  time  to  lessen  the  friction  (Fig.  90). 

If  tortoises  or  turtles  are  available,  the  much  larger  heart  of  these 
animals  may  be  used  for  Experiments  5  (2)  (a)  and  (6).  The  animal 
having  been  killed  by  cutting  off  its  head,  the  ventral  portion  of  the 
carapace  is  detached  by  the  saw.  The  pericardium  can  now  be  slit 
open,  and  the  pads  of  the  levers  arranged  on  auricles  and  ventricle 


Fig.  89. — Apparatus  for  obtaining  a  Simultaneous  Tracing  of  Auricular  and 
Ventricular  Contractions. 


respectively,  as  in  Experiment  5  (2)  [a),  without  further  disturbing 
the  heart.  Or  the  heart  may  be  removed,  together  with  the  upper 
portion  of  the  body,  the  pericardium  opened,  and  the  liver  cut  away. 
The  aortic  trunk  is  then  divided,  and  the  portion  of  it  attached  to 
the  heart  grasped  by  a  small  forceps  clamp.  Fine  silk  ligatures  are 
attached  to  the  apex  of  the  ventricle  and  the  top  of  the  right  auricle. 
The  vagus  nerves  are  exposed  in  the  neck,  ligatcd,  and  divided.  The 
upper  portion  of  the  body  is  supported  on  a  stand.  The  forceps  grasp- 
ing the  aorta  is  fixed  in  an  ordinary  holder,  and  the  threads  are  attached 
to  the  levers,  as  in  Experiment  5  (2)  {b). 

With  the  vagi,  Experiment  7  may  be  performed.  It  must  be  remem- 
bered that  the  activity  of  the  two  vagi  is  unequal  in  the  tortoise,  the 
right  being  the  more  active. 

6.  Dissection  of  the  Vagus  and  Cardiac  Sympathetic  Nerves  in  the 
Frog. — (i)  Put  the  tissues  in  the  region  of  the  neck  on  the  stretch  by 
passing  into  the  gullet  a  narrow  test-tube  or  a  thick  glass  rod  moistened 
with  water,  and  by  pinning  apart  the  anterior  limbs.     Expose  the  heart 


PRACTICAL  EXERCISES 


195 


GK] 


by  cutting  through  the  pectoral  girdle  in  the  way  described  in  2  (p.  192). 
On  clearing  away  a  little  connective  tissue  and  muscle  with  a  seeker, 
three  large  nerves  will  come  into  view.  The  upper  is  the  glosso- 
pharyngeal, the  lower  the  hypoglossal;  the  vagus  crosses  diagonally 
between  them  (Fig.  91).  Above  the  vagus  trunk,  running  parallel  to 
it,  and  separated  from  it 
by  a  thin  muscle  and  a  m 
bloodvessel  (the  carotid 
artery),  lies  its  larvmgcal 
branch.  The  vagus  should 
be  traced  up  to  the  gang- 
•lion  situated  on  it  near  its 
exit  from  the  skull. 

(2)  Then  cut  away  the 
lower  jaw,  dividing  and 
reflecting  the  membrane 
covering  the  roof  of  the 
mouth.  At  the  junction 
of  the  skull  and  the  back- 
bone will  be  seen  on  each 
side  the  levator  anguli 
scapulae  muscle  (Fig.  gz). 
Remove  this  muscle  care- 
fully with  fine  forceps. 
Clear  away  a  little  con- 
nective tissue  lying  just 
over  the  upper  cervical 
vertebra3,  and  the  sym- 
pathetic chain,  with  its 
ganglia,  will  be  seen.  Pass 
a  fine  silk  thread  beneath 
the  sympathetic  about  the 
level  of  the  large  brachial 
nerve,  by  means  of  a 
sewing-needle  which  has 
been  slightly  bent  in  a 
flame  and  fastened  in  a 
handle.  Tie  the  ligature, 
divide  the  sympathetic  be- 
low it,  and  isolate  it  care- 
fully with  fine  scissors  up 
to  its  junction  with  the 
vagus  ganglion. 

Batteries — To  set  up  a 
Danicll  Cell. — Fill  the  por- 
ous pot  (Fig.  219,  p.  597), 
previously  well  soaked  in 
water,  with  dilute  sulph- 
uric acid  (i  part  of  com- 
mercial acid  to  10  or  15 
parts  of  water)  to  within 


Fig.  90.— Arrangement  for  recording  Auriculae 
and  Ventricular  Contractions  (and  studying  the 
Influence  of  Temperature  of  the  Heart).  C, 
clamp  holdmg  the  heart  at  the  auriculo-ven- 
tricular  groove;  P,  pulley  round  which  a  thread 
attached  to  the  ape.x  of  the  ventricle  passes  to 
the  lever  L';  L.  lever  connected  with  auricle. 
(The  rest  of  the  arrangement  is  for  studying  the 
influence  of  temperature  on  the  heart  and  its 
nerves,  G  being  a  \-cssel  filled  with  physiological 
salt  solution  in  which  the  heart  is  immersed;  R, 
an  inflow  tube  from  a  reservoir  containing  salt 
solution  at  the  temperature  required;  O',  an  out- 
flow tube  by  which  G  may  be  emptied  into  the 
beaker  B';  O,  a  tube  passing  to  the  beaker  B  to 
prevent  overflow  fruin  G;  T.  a  thermometer.) 


\\  inches  of  the  brim,  and  place  in  it  the  piece  of  amalgamated  zinc.  If 
the  zinc  is  not  properly  amalgamated,  leave  it  in  the  pot  for  a  minute  or 
two  to  clean  its  surface.  Then  lift  it  out,  pour  over  it  a  little  niercury, 
and  rub  the  mercury  thoroughly  over  it  with  a  cloth.  Put  the  pot 
into  the  outer  vessel,  which  contains  the  copper  plate,  and  is  filled 
with  a  saturated  solution  of  sulphate  of  copper,  with  some  undissolved 


196  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

crystals  to  keep  it  saturated.  After  using  the  Daniell,  it  must  always 
be  taken  down.  The  outer  pot  is  left  with  the  copper  plate  and  the 
sulphate  solution  in  it.  The  zinc  is  washed  and  brushed  bright.  The 
sulphuric  acid  is  poured  into  the  stock  bottle,  and  the  porous  pot  put 
into  a  large  jar  of  water  to  soak. 

The  Bichromate  Cell  contains  only  one  liquid — a  mixture  of  i  part 
of  sulphuric  acid  with  4  parts  of  a  10  per  cent,  solution  of  potassium 
bicJiromate.  In  this  is  placed  one,  or  in  some  forms  two,  carbon 
plates  and  a  plate  of  amalgamated  zinc.  After  using  the  battery,  take 
the  zinc  out  of  the  liquid. 

The  Leclanche  battery  consists  of  a  porous  pot  filled  with  a  mixture 
of  manganese  dioxide  and  carbon  packed  around  a  carbon  plate,  which 
forms  the  positive  pole.  The  pot  stands  in  an  outer  jar  of  glass  filled 
witli  a  saturated  solution  of  ammonium  chloride,  into  which  dips  an 
amalgamated  zinc  rod,  which  constitutes  the  negative  pole.  Various 
forms  of  dry  batteries  can  be  conveniently  used  for  running  indue tion- 

Al     ,  coils  or  time-markers,  but  are  not 

Cy^iii  f''"i     t   :|i|i  adapted  for  yielding  constant  cur- 

ll'  Mm  rents  of  long  duration. 

^      -'-^     y^pi-M^^\  the  Frog, — Make  the  same  arrange- 

'Jm^       ^\\  mcnts  as  in  5  (i)  (p.  192),  but  in 

{^  ^      M  /  /    addition     set     up    an    induction 

7      '  ^      \LqryQ^eaL    machine    arranged   for   an   inter- 

/  ir^^^    \\  branch  0/    rupted    current   (Fig.  93),   with  a 

("^^—^1  ^^Wk     h      '^'^'^     Daniell,  a  bichromate,  a  Leclanche, 
^X.      I  I    -^^^^^^-^  '^^  ^  *^^y  ^^^^  ^"  ^^^  primary  circuit, 

u            /^^=^  I       ^^     ^~^        which  should  also  include  a  simple 
nypo^/0im-\^^^J^^       /^  \  Y      key.     Insert  a  short-circuiting  key 

yadui  - -^^^^^  ^^^kNv      \  ^^  ^^®  secondary  circuit.     Attach 

/  /-^^^^L^^^'^^^^%\    \         the  electrodes  to  the  short-circuit- 

y  'If   \   fl  'M    K       ^^^  ^^y*  P^^^^  ^^  secondary  coil 

'  {[■  #^4^  //)  \  ^P  towards  the  primary  until  the 
1  \  '3  ^^^\\/^  I  shocks  are  distinctly  felt  on  the 
>  \  m  tiehri  Y  J  /  tongue  when  the  Neef 's  hammer  is 
\J  \      Y  set  going  and  the  short-circuiting 

'•Lijri^         '      /  key  opened.     Pith  the  brain  of  a 

Fig.  91.— The  Relations  of  the  Vagus        ^^og,  expose  the  heart,  dissect  out 
in  the  Frog.  the  vagus  on  one  side,  ligature  it 

as  high  up  as  possible,  and  divide 
above  the  ligature.  Fasten  tlie  electrodes  on  the  cork  plate  by  means 
of  an  indiarubber  band,  and  lay  the  vagus  on  them.  Set  the  drum 
off  (at  slow  speed).  After  a  dozen  heart-beats  have  been  recorded, 
stimulate  the  vagus  for  two  or  three  seconds  by  opening  the  short- 
circuiting  key.  If  the  nerve  is  active,  the  heart  will  be  slowed, 
weakened,  or  stopped.  In  the  last  case  the  lever  will  trace  an  unbroken 
straight  line ;  but  even  if  the  stimulation  is  continued  the  beats  will 
again  begin. 

8.  Stimulation  of  the  Junction  of  the  Sinus  and  Auricles. — After  a 
sufficient  number  of  the  observations  described  in  7  have  been  taken 
with  varying  time  and  strength  of  stimulation,  take  the  writing-points 
off  the  drum,  apply  the  electrodes  directly  to  the  crescent  at  the  junc- 
tion of  the  sinus  venosus  with  the  right  auricle,  and  stimulate.  The 
heart  wiU  be  affected  very  much  in  the  same  way  as  by  stimulation  of 
the  vagus,  except  that  during  the  actual  stimulation  its  beats  may  be 
quickened  and  the  inhibition  may  only  begin  after  the  electrodes  have 
been  removed  (Fig.  70,  p.  158). 


PRACTICAL  EXERCISES 


T.97 


IAS 


g.  Effect  of  Muscarine  (or  Pilocarpine)  and  Atropine. — Paint  on  the 
sinus  vcnosus  witli  a  small  caracl's-hair  brush  a  very  dilute  solution  of 
muscarine  (or  of  pilocarpine).  The  heart  will  soon  be  seen  to  beat 
more  slowly,  and  will  ultimately  stop  in  diastole.  Now  apply  a  dilute 
solution  of  sulphate  of  atropine  to  the  sinus.  The  heart  will  again 
begin  to  beat.  Stimulation  of  the  vagus  will  now  cause  no  inhibition 
of  the  heart,  because  its  endings  have  been  paralyzed  by  atropine. 
(Muscarine  or  pilocarpine  has  also  been  applied  to  the  heart,  but  it 
could  be  shown  by  a  separate  experiment  that  atropine  by  itself  has 
the  same  effect  on  the  vagus  endings — p.  164.) 

10.  Stannius'  Experiment. — Pith  a  frog.  Expose  the  heart  in  the 
way  described  under  2  (p.  191).  Ligature  the  frsenum  with  a  fine  silk 
thread,  and  use  the  thread  to  manipulate  the  heart.  With  a  curved 
needle  pass  a  moistened  silk  thread  between  the  aorta  and  the  superior 
vena  cava,  and  tie  it  round  the 
junction  of  the  sinus  and  right 
auricle  (Fig.  86).  The  auricles 
and  ventricle  stop  beating  as 
soon  as  the  ligature  is  tightened. 
The  sinus  \^enosus  goes  on  beat- 
ing. Now  separate  the  ven- 
tricle from  the  rest  of  the  heart 
by  an  incision  through  the 
auriculo-ventricular  groove,  or 
tie  a  second  ligature  in  the 
groove.  The  ventricle  begins 
to  beat  again,  the  auricle  re- 
maining quiescent  in  diastole 
(p.  165).  Occasionally  both 
auricle  and  ventricle,  or  only 
the  auricle,  may  begin  to  beat. 

11.  Stimulation  of  Cardiac 
Sympathetic  Fibres  in  the  Frog 
■ — (i)  1)1  the  vagosympathetic 
after  the  inhibitory  fibres  have 
been  cut  out  by  atropine. — 
Arrange  everything  as  in  7 
(p.  196).  Assure  yourself,  by 
stimulating  the  vagus,  that  it 
inhibits  the  heart,  and  take 
a  tracing  during  stimulation. 
Then  paint  a  dilute  solution 
of  atropine  on  the  sinus. 
Stimulation  of  the  vagus,  which  is  really  the  vago-sympathctic  (see 
Fig.  92),  will  now  cause,  not  inhibition,  but  augmentation  (increase 
in  rate  or  force,  or  both),  since  the  endings  of  the  inhibitory  fibres  have 
been  paralyzed  by  atropine.  The  strength  of  the  stimulating  current 
required  to  bring  out  a  typical  augmentor  effect  is  greater  than  that 
needed  to  stimulate  the  inhibitory  fibres.  Take  a  tracing  to  show 
augmentation  produced  by  stimulating  the  nerve. 

(2)  By  direct  stimulation  of  the  cervical  sympathetic. — Make  the  same 
arrangements  as  in  11  (i),  but,  instead  of  isolating  the  vagus,  dissect 
out  tlu?  sympathetic  on  one  side  in  the  manner  described  in  6  (2)  (p.  195), 
and  do  not  apply  atropine  to  the  heart.  Lay  the  upper  (cephalic)  end 
of  the  sjan pathetic  on  very  fine  and  well-insulated  electrodes,  and 
stimulate  (Fig.  76,  p.  165).  (To  insulate  electrodes  the  points  may  be 
covered  with  melted  paraffin.     When  the  paraffin  has  cooled,  a  narrow 


Fig.  92.  —  Relation  of  the  Sympathetic  to 
the  Vagus  in  the  Frog  (after  Gaskell). 
Sym,  s>Tnpathetic  chain ;  G,  ganglion  of 
the  vagus;  VS.  vago -sympathetic ;  GP, 
glosso- pharyngeal  nerve;  LAS,  levator 
anguli  scapulaj  muscle ;  SA,  subclavian 
artery;  A,  descending  aorta;  V,  vertebral 
column;  OC,  occipital  part  of  skull;  1-4, 
spinal  nerves. 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


groove,  just  sufficient  to  lay  bare  the  wires  on  the  upper  side,  is  made 
in  it,  and  the  nerve  is  laid  in  this  groove.) 

Experiments  7,  ii  (i)  and  11  (2)  will  be  rendered  more  exact  by 
connecting  a  second  electro-magnetic  signal  with  a  Pohl's  commutator 
without  cross-wires  (Fig.  94),  in  such  a  way  that  the  circuit  is  inter- 
rupted at  the  instant  when  stimulation  begins. 

12.  The  Action  of  Inorganic  Salts  on  Heart-Muscle. — Expose  and 
remove  the  heart  of  a  tortoise  or  turtle  (p.  194).  Cut  off  the  apical  two- 
thirds  of  the  ventricle  by  an  incision  parallel  to  the  auriculo-ventricular 
groove.  By  a  second  parallel  cut  remove  a  ring  of  tissue  2  or  3  milli- 
metres wide  from  the  upper  end  of  this  portion  of  the  ventricle.  Divide 
the  ring  at  opposite  ends  of  a  diameter,  so  as  to  form  two  strips.  Tie 
a  fine  silk  thread  to  each  end  of  one  strip.  Attach  one  of  the  threads 
to  the  short  limb  of  a  glass  rod  bent  at  right  angles,  so  that  it  can  be 
immersed  at  will  in  a  beaker.  The  other  end  of  the  rod  is  fixed  in  a 
holder  sliding  on  a  stand.     Attach  the  second  thread  to  the  short  arm 


Fig.  93. — Arrangement  of  Induction  Machine  for  Tetanus.  B,  battery;  K,  simple 
key;  P,  primary  coil;  S,  secondary  coil;  A,  C,  binding  screws  to  be  connected 
with  battery  for  single  shocks;  F,  G,  binding  screws  for  tetanizing  current;  N, 
Neefs  hammer;  D,  short-circuiting  key  in  secondary;  E,  electrodes.  D  and  E 
are  drawn  to  a  much  larger  scale  than  the  rest  of  the  figure. 

of  a  counterpoised  lever  arranged  to  write  on  a  slowly-moving  drum. 
If  the  strip  is  still  beating,  wait  till  the  contractions  have  ceased ;  then 
(i)  Immerse  the  strip  in  a  beaker  filled  with  o'j  per  cent,  solution  of 
sodium  chloride.  After  a  time  it  begins  to  beat  rhythmically.  The 
contractions  become  rapidly  stronger,  and  then  after  a  while  diminish, 
and  gradually  cease.  The  tone  or  tonus  of  the  strip  is  diminished  by 
the  solution. 

(2)  Arrange  the  other  strip  in  the  same  way,  and  immerse  it  in  a 
solution  of  calcium  chloride  (about  i  per  cent.)  isotonic  with  the  sodium 
chloride  solution  used  in  (i).  If  the  strip  is  contracting,  the  contrac- 
tions will  cease.  Rhythmical  contractions  will  not  appear  as  in  the 
sodium  chloride  solution.     The  tone  of  the  strip  may  be  increased. 

(3)  Remove  most  of  the  calcium  chloride  solution  from  the  beaker, 
and  fill  it  up  with  07  per  cent,  sodium  chloride  solution.  The  rhythmi- 
cal contractions  will  appear  after  a  longer  or  ^shorter  latent  period,  and 
will  be  stronger  and  last  for  a  longer  time  than  in  the  sodium  chloride 
solution  alone. 

(4)  Immerse  a  fresh  strip  in  a  solution  containing  sodium   chloride 


PRACTICAL  EXERCISES  rgg 

(o'7  per  cent.),  calcium  chloride  (0025  per  cent.),  and  potassium 
chloride  (003  per  cent.)  (a  modified  Ringer's  solution).  A  longer 
series  of  rhj-thmical  contractions  will  be  obtained  than  in  either  (i) 
or  (3).  That  this  is  not  due  to  the  potassium  chloride  acting  alone 
can  be  showTi  by  immersing  a  strip  in  a  solution  of  potassium  chloride 
(about  09  per  cent.)  isotonic  with  the  sodium  chloride  solution  used 
in  (i).     No  contractions  will  be  caused. 

13.  The  Action  of  the  Mammalian  Heart. — Inject  under  the  skin  of  a 
dog  (preferably  a  small  one)  i  c.c.  of  a  2  per  cent,  solution  of  morphine 
hydrochlorate  for  every  kilo  of  body-weight.  As  soon  as  the  morphine 
has  taken  effect  (in  15  to  30  minutes,  but  better  after  an  hour),  fasten 
the  animal  back  down  on  a  holder  (as  in  Fig.  135,  p.  295),  pushing  the 
mouth-pin  behind  the  canine  teeth  and  screwing  the  nut  home.*  In 
the  meantime  select  a  tracheal  cannulaf  of  suitable  size,  and  get  ready 
instruments  for  dissection — one  or  two  pairs  of  artery-forceps,  a  pair 
of   arterj'-clamps    (bulldog   pattern),    two   or   three   glass   cannulas   of 


■B' 

Fig.  94. — Arrangement  for  recording  the  Beginning  and  End  of  Stimulation.  C, 
Pohl's  commutator  without  cross-wires;  B,  battery  in  circuit  of  primary  coil  P; 
B',  battery  in  circuit  of  electro-magnetic  signal  T;  K,  simple  key  in  primary 
circuit;  S,  secondary  coil.  When  the  bridge  of  the  commutator  is  tilted  into 
the  position  shown  in  the  figure,  the  primary  circuit  is  closed  and  the  circuit  of 
the  signal  broken. 

various  sizes  for  bloodvessels,  ten  strong  waxed  ligatures,  sponges, 
hot  water,  a  towel  or  two,  and  a  pair  of  bellows  to  be  connected  with 
the  tracheal  cannula  when  the  chest  is  opened.     Arrange  an  induction- 

*  A  simple  but  efficient  and  convenient  holder  for  a  dog  may  be  easily 
constructed  as  follows:  Take  a  board  of  the  length  required  (ai  to  5  feet, 
according  to  the  size  of  the  dog).  At  one  end  fasten  two  short  upright  wooden 
pins,  with  a  clear  space  of  4  to  6  inches  between  them.  These  are  pierced 
from  side  to  side  with  four  or  five  holes  at  different  heights.  An  iron  pin  passes 
behind  the  canine  teeth  of  the  animal  through  two  corresponding  holes  in  the 
uprights,  and  the  muzzle  is  tied  over  this  by  a  cord  which  secures  the  head. 
For  a  large  dog  an  upper  pair  of  holes  is  used,  for  a  small  dog  a  lower  pair. 
The  feet  are  fastened  by  cords  to  staples  inserted  into  the  sides  of  the  board, 
the  fore-legs  being  drawn  tailwards  for  all  operations  on  the  neck  or  head, 
headwards  for  operations  on  the  thorax.  A  rabbit-holder  can  be  made  in 
exactly  the  same  way. 

t  A  tracheal  cannula  is  easily  made  by  heating  a  piece  of  glass  tubing, 
about  6  inches  long,  a  short  distance  from  one  end,  and  drawing  it  out  sUghtly 
so  as  to  form  a  '  neck.'  The  tubing  is  then  bent  about  its  middle  to  an  obtuse 
angle,  and  the  end  next  the  neck  is  ground  obliquely  on  a  stone.  The  diameter 
of  the  cannula  should  be  about  the  same  as  that  of  the  trachea,  into  which  it 
is  to  be  inserted  by  its  oblique  end. 


200  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

coil  and  electrodes  for  a  tetanizing  current  (Fig.  93,  p.  198),  With 
scissors  curved  on  the  flat  clip  away  the  hair  from  the  front  of  the 
neck.  Put  the  hair  carefully  away,  and  remove  all  the  loose  hairs 
with  a  wet  sponge  so  that  they  may  not  get  into  the  wounds.  Give  ether, 
or  pour  into  the  stomach  by  a  tube  5  c.c.  of  a  o"5  per  cent,  solution 
of  chloroform  in  10  per  cent,  alcohol  per  kilo  of  bodj^-weight,  diluted 
before  administration  with  3  or  4  volumes  of  water  (Grehant's  method). 
To  put  a  Cannula  in  the  Trachea. — -The  hair  having  been  clipped  in 
the  middle  line  of  the  neck  and  the  skin  shaved,  a  mesial  incision  is 
to  be  made,  beginning  a  little  below  the  cricoid  cartilage,  which  can 
be  felt  with  the  fmger.  The  trachea  is  then  cleared  from  its  attach- 
ments by  forceps  or  a  blunt  needle,  and  two  strong  ligatures  are  passed 
beneath  it.  A  single  loop  is  placed  on  each  of  these,  but  is  not  drawn 
tight.  Raising  the  trachea  by  means  of  the  upper  ligature,  the  student 
makes  a  longitudinal  incision  through  two  or  three  of  the  cartilaginous 
rings,  inserts  the  cannula,  and  ties  the  lower  ligature  firmly  around  its 
neck.     The  upper  ligature  can  now  be  withdrawn. 

Clip  off  the  hair  on  each  side  of  the  sternum.  Make  an  incision  on 
each  side  through  the  skin  and  down  to  the  costal  cartilages  about 
2  inches  from  the  edge  of  the  breast-bone,  and  long  enough  to  expose 
about  four  costal  cartilages  (say,  3rd  to  6th).  With  a  curved  needle 
pass  waxed  ligatures  round  the  cartilages,  and  tie  firmly  to  compress 
the  intercostal  vessels.  The  bellows  should  now,  or  earlier  if  any 
symptoms  of  impeded  respiration  have  appeared,  be  connected  with 
one  end  of  the  horizontal  limb  of  a  glass  T-piece,  the  other  end  of 
which  is  similarly  connected  with  the  tracheal  cannula.  The  stem  of 
the  T-piece  is  provided  with  a  short  piece  of  rubber  tubing,  which, 
when  artificial  respiration  is  being  carried  on,  is  to  be  alternately  closed 
and  opened — closed  during  inflation  of  the  lungs,  and  opened  when 
the  air  is  to  be  allowed  to  escape  from  them.  Or  a  screw-clamp  may 
be  adjusted  on  the  piece  of  tubing  so  that  the  opening  is  sufficiently 
narrow  to  permit  the  lungs  to  be  properly  inflated  when  the  bellows 
are  compressed,  and  yet  sufficiently  wide  to  permit  easy  escape  of  the 
air  and  collapse  of  the  lungs  at  the  end  of  each  inflation.  Ether  may, 
when  necessary,  be  administered,  b}^  inserting  between  the  T-piece  and 
the  tube  from  the  bellows  an  ether  bottle  with  two  tubes  passing  through 
the  cork  to  within  an  inch  or  two  of  the  ether.  If  the  cannula  has  a 
side-opening,  as  is  usually  the  case  v/ith  metal  cannulas,  the  T-piece 
may  be  dispensed  with.  One  student  should  take  sole  charge  of  the 
artificial  respiration,  which  ought  to  be  begun  as  soon  as  the  chest  has 
been  opened,  and  continued  at  the  rate  of  about  twenty  inflations 
per  minute.  The  costal  cartilages  are  rapidly  cut  through  with  strong 
scissors  just  on  the  sternal  side  of  the  ligatures,  the  artificial  respira- 
tion being  suspended  for  an  instant,  as  each  cut  is  niade,  to  avoid 
wounding  the  lungs.  The  sternum  is  divided  at  its  lower  end  and 
turned  up.  If  there  is  much  bleeding  a  ligature  should  be  tied  round 
its  upper  end.  With  a  curved  needle  a  ligature  is  passed  below  the 
internal  mammary  arteries  as  they  approach  the  sternum.  That  bone 
may  now  be  removed,  and  the  heart,  enclo.sed  in  the  pericardium,  comes 
into  view.  A  tliread  is  passed  with  a  suture-needle  through  each  side  of 
the  pericardium,  which  is  then  stitched  to  the  chest-wall  and  opened. 

[a)  Note  the  various  portions  of  the  heart,  right  and  left  ventricles, 
right  and  left  auricles,  with  the  auricular  app  ndiccs.  Feel  the  heart 
with  the  hand,  and  observe  that  the  right  ventricle  is  softer  and  has 
thinner  walls  than  the  left,  and  that  the  auricles  are  softer  than  the 
ventricles.  Note  how  all  the  parts  of  the  heart  harden  in  the  han.! 
during  systole  and  soften  during  diastole  (pp.  86,  90). 


PRACTICAL  EXERCISES 


20I 


(b)  Dissect  out  the  vago-sympathetic  on  one  side  in  the  neck  of  the 
dog.  The  guide  to  the  nerve  is  the  carotid  artery.  These  two  struc- 
tures and  the  internal  jugu- 
lar vein  lie  side  by  side  in 
a  common  sheath.  Feel 
for  the  artery  a  little  ex- 
ternal to  the  trachea,  cut 
down  on  it,  open  the  sheath , 
isolate  the  \-ago  -  sympa- 
thetic for  about  an  inch, 
pass  two  ligatures  under  it, 
tie  them,  and  divide  be- 
tween the  ligatures.  The 
peripheral  and  central  ends 
of  the  nerve  may  now 
be  successively  stimulated. 
Stimulation  of  the  peri- 
pheral end  causes  slowing 
of  the  heart,  or  stoppage 
in  diastole.  Feel  that  it 
softens  when  it  stops.  It 
soon  begins  to  beat  again. 
Stimulation  of  the  central 
end  of  the  vago-sympa- 
thetic may  or  may  not 
cause  inhibition .  If  it  does, 
expose  the  other  vago- 
sympathetic, divide  it,  and 
repeat  the  stimulation  of 
the  central  end.  There  will 
now  be  no  inhibition  of  the 
heart.  Incidentally  it  may 
be  seen  that  stimulation 
of  the  central  end  of  the 
vago  -  sympathetic  causes 
strong,  though,  of  course, 
withopened  chest, abortive, 
respiratory  movements. 

(c)  Pith  a  frog  (brain 
and  cord),  dissect  out  the 
sciatic  nerve  on  one  side  up 
to  the  sacral  plexus.  Cut 
off  the  whole  leg.  Drop  the 
cut  end  of  the  nerve  on  the 
heart,  and  hold  the  prep- 
aration so  that  the  nerve 
touches  the  heart  also  by 
its  longitudinal  surface.  At 
each  cardiac  beat  the  nerve 
is  stimulated  by  the  action 
current  (p.  807),  and  the 
muscles  of  the  leg  contract. 

{d)  Raise  the  board  so 
that  the  head  of  the  animal 
is  down  and  the  hind-feet 
up,  and  note  whether  there 
is  any  effect  on  the  action 


B 


I 


i 


Fig.  95- — Myocardiograph  of  Adami  and  Roy 
(modified  by  Cushny  and  Matthews).  AB.  a 
perpendicular  rod  descending  from  a  universal 
joint,  which  is  not  shown  in  the  figure;  CD.  a 
brass  sheath,  moving  easily  on  the  rod,  and 
bearing  on  its  upper  end  an  ivory  pulley,  and  at 
its  lower  end  a  horizontal  bar,  which  is  inter- 
rupted by  a  plate  of  hard  rubber,  I.  The  per- 
pendicular rod  EF  moves  on  the  horizontal  bar 
by  the  hinge-joint,  J.  EF  is  hooked  at  one  end 
for  attachment  to  the  heart,  and  bored  at  the 
other  for  a  thread  which,  passing  over  the  pullev 
at  C,  passes  through  the  universal  joint  and 
moves  a  writing  lever  not  shoM-n  in  the  figure. 
CD  is  prevented  from  moving  up  AB  by  a  ring  of 
brass,  G.  which  is  screwed  to  .AB,  but  is  not 
attached  to  CD ;  the  hook  F  can  therefore  move 
to  and  from  AB,  and  can  rotate  round  it,  while 
it  cannot  move  up  or  down.  The  hooks  F  and  B 
are  insulated  from  each  other  by  the  hard  rubber. 
I.  H  is  a  binding  post  through  which,  and 
tlirough  another  connected  with  A,  induction 
shocks  may  be  sent  at  will  into  the  portion 
ol  the  heart  lying  between  the  hooks. 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


and  filling  of  the  heart.     Repeat  the  observation  with  head  up  and 

feet  down. 

[e]  Compress  the  aorta  with  the  fingers,  and  observe  the  effect  on 

the  degiee  of  dilatation  of  the  various  cavities  of  the  heart.     Repeat 

the  experiment  with  the  inferior  vena  cava,  and  compare  the  results. 

if)  Smoke  a  drum.  Insert  the 
hooks  of  the  myocardiograph  (Fig.  95) 
into  the  ventricle,  taking  care  not 
to  penetrate  deeply  into  the  wall. 
Arrange  the  lever  to  write  on  the 
drum.  While  a  tracing  is  being 
taken  stimulate  the  peripheral  end  of 
the  vagus.  Unhook  the  cardiograph. 
(g)  Stop  the  artificial  respiration, 
and  observe  the  changes  which  take 
place  in  the  auricles  and  ventricles, 
comparing  particularly  the  right  side 
of  the  heart  with  the  left.  Before 
the  heart  has  stopped  beating,  re- 
commence the  artificial  respiration. 

(h)  Connect  a  cylinder  of  oxygen 
with  a  good-sized  rubber  catheter, 


D  fc 

Fig.  96. — Arrangement  to  illustrate  Action  of  Cardiac  Valves  in  the  Heart  of  an  Ox 
(Gad).  C,  glass  window  in  left  auricle;  D,  window  in  aorta;  E,  tube  inserted 
through  apex  of  heart  into  left  ventricle  and  connected  with  pump  P;  A,  side 
tube  on  E,  through  which  wires  are  connected  with  a  tiny  incandescent  lamp  in 
the  ventricle;  W,  water  in  bottle  B;  T,  T',  tubes. 

and  pass  the  catheter  down  the  tracheal  cannula  or  through  a  separate 
opening  in  the  trachea.  Allow  a  small  stream  of  oxygen  to  flow  into 
the  lungs.  Artificial  respiration  is  now  unnecessary.  The  lungs 
remain  at  rest,  yet  the  blood  is  sufficiently  oxygenated,  and  the  heart 
goes  on  beating.  The  myocardiographic  tracing  thus  goes  on  undis- 
turbed by  respiratory  movements. 

{»)  Stop  the  oxygen,  and  resume  the  artificial  respiration.     Make  a 


PRACTICAL  EXERCISES 


203 


small  penetrating  wound  with  a  scalpel  in  the  left  ventricle.  Observe 
the  course  of  the  hremorrhage,  and  note  especially  the  difference  in 
systole  and  diastole. 

ij)  Lay  the  electrodes  on  the  heart,  and  stimulate  it  with  a  strong 
interrupted  current.  The  character  of  the  contraction  soon  becomes 
profoundly  altered.  Shallow,  irregular 
contractions  flicker  over  the  surface,  with 
a  kind  of  simmering  movement  sugges- 
tive of  a  boiling  pot  (delirium  cordis, 
fibrillar  contraction).  Now  kill  the  ani- 
mal by  stopping  the  artificial  respiration. 
Observe  how  long  the  heart  continues  to 
beat,  and  which  of  its  divisions  stops  last. 

(k)  Make  a  dissection  of  the  cervical 
sympathetic  up  to  the  superior  cervical 
ganglion,  and  dowTi  through  the  inferior 
cervical  ganglion  to  the  stellate  or  first 
thoracic  ganglion.  Make  out  the  annulus 
of  Vieussens  and  the  cardiac  sympa- 
thetic (accelerator)  branches  going  off 
from  the  annulus  or  the  inferior  cervical 
ganglion  to  the  cardiac  plexus  (Fig.  74, 

p.   102). 

14.  Perfusion   of  the   Isolated   Mam-  U , 

malian  Heart. — The  heart  of  a  dog  em-  [■  - -4rlr-"--~3 — CI 

ployed  for  some  other  experiment  may 
be  used.  Or  a  rabbit  may  be  killed  by 
a  blow  on  the  back  of  the  head,  rnd 
the  heart  at  once  removed.  The  aorta 
should  not  be  cut  off  too  short.  Tie  a 
cannula  into  the  aorta  and  attach  it  to 
a  T-piece  connected  by  rubber  tubes, 
which  must  be  perfectly  clean,  with  two 
bottles,  one  containing  Ringer's  solution 
(pp.  66,  iqq),  preferably  that  made  with 
dextrose,  the  other  containing  defibrin- 
ated  blood  diluted  with  Ringer's  solu- 
tion. The  defibrinated  blood  should  be 
strained  so  as  to  remove  any  small  pieces 
of  fibrin.  The  bottles  are  supported  on  a 
high  stand,  so  that  the  level  of  the  bottles 
above  the  heart  can  be  altered,  and  the 
pressure  of  the  perfusion  liquid  thus 
varied.  Perfusion  may  be  begun  with 
Ringer,  to  wash  out  any  remaining  blood 
and  obviate  the  possible  formation  of 
clots  in  the  small  vessels.  Oxygen  is 
allowed  to  bubble  through  the  Ringer's 
solution,  but  this  is  not  necessary  for  the 
blood,  since,  if  shaken  up,  it  will  retain 
far  more  oxygen  than  the  Ringer's  solu- 
tion. The  temperature  of  the  liquids 
should  be  at  about  40°  C.  when  nearing  the  heart.  This  can  be  most 
easily  insured  by  interposing  a  worm  immersed  in  a  heated  bath  or 
other  heating  arrangement  between  the  cannula  and  the  T-tube.  and  for 
the  study  of  its  movements  by  inspection  the  heart  itself  can  be  placed 
in  a  glass  vessel  immersed  in  the  bath.     When  records  of  the  contractions 


Fig.  97- — Mammalian  Heart  Per- 
fusion Apparatus  (Gunn).  a, 
Liebig  condenser,  cut  off  as 
shown ;  b,  inlet  for  the  warm 
water ;  d,  thermometer  almost 
filling  up  the  lumen  of  the  thin 
glass  tube  c  ;  e,  cork  ;  /,  cannula 
for  aorta  fitted  with  a  collar  of 
rubber  tubing,  g,  in  the  end  of 
the  tube  c  ;  h.  Y-tube  connected 
with  two  reser%'oirs,  one  contain- 
ing Ringer's  solution,  the  other 
any  other  liquid  which  is  to  be 
perfused. 


204 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


are  to  be  obtained,  threads  are  attached  to  the  auricle  and  to  the  apex 
of  the  ventricle.  The  heart  is  suspended  by  fastening  the  cannula  in  a 
holder  on  a  stand,  and  the  threads,  after  passing  over  pulleys  to  give 
them  a  convenient  direction,  are  attached  to  writing-levers. 

As  the  heart  cannot  now  be  easily  kept  immersed  in  the  bath,  it  is 
suspended  in  the  air,  and  can  be  kept  warm  by  the  following  simple 
arrangement :  A  copper  pipe  about  4  inches  long  is  slit  on  one  side,  and 
on  the  opposite  side  is  screwed  or  riveted  to  a  copper  rod,  under  which 
is  hung  a  spirit-lamp.  The  lamp  is  adjusted  at  such  a  point  on  the  rod 
that  when  the  copper  tube  is  placed  around  the  heart  the  heat  conducted 
along  the  rod  keeps  the  air  around  the  heart  at  about  body-temperature. 
The  perfusion  liquid  before  it  enters  the  heart  may  be  heated  thus: 
A  Liebig's  condenser  is  cut  through  the  middle,  and  the  large  end 
closed  by  a  paraffined  cork.  A  glass  tube  is  run  down  from  the  top 
through  this  cork,  and  the  aorta  is  attached  directly  to  this,  so  that 
the  heart  is  very  near  the  condenser.  This  tube  is  mostly  filled  up  by 
a  thermometer,  so  that  the  perfusion  liquid  passes  through  it  in  a  thin 
stream  which  is  easily  heated  by  the  water  in  the  condenser,  which 
P  A.  contains  a  second  ther- 

mometer. This  water  is 
kept  constantly  flowing 
through  the  condenser 
from  a  heated  bath.  The 
T-piece  connecting  with 
the  perfusion  bottles  is 
attached  to  the  upper 
end  of  the  glass  tube 
to  which  the  heart  is 
attached  (Gunn  and 
Cusliny). 

15.  Action  of  the 
Valves  of  the  Heart. — 
(i)  Study  the  action  of 
the  valves  of  the  ox- 
heart,  connected  with 
the  pump  P  and  bottle  B 
in  the  artificial  scheme, 
as  shown  in  Fig.  96.  The 
cavity  of  the  heart  is 
illuminated  by  means  of 
a  small  electric  lamp,  the 
wires  of  which  pass  in  at 


J" 


o 

Fig.  98. — Diagram  of  Valves  of  the  Heart.  The 
valves  are  supposed  to  be  viewed  from  above,  the 
am-icles  having  been  partially  removed.  A,  aorta 
with  semilimar  valve;  B,  pulmonary  artery  and 
valve;  C,  tricuspid,  and  D,  mitral  valve;  E,  right, 
and  F,  left  coronary  artery ;  G,  wall  of  right,  and  H, 
of  left  auricle,  I,  wall  of  right,  and  J,  of  left  ventricle. 


A.  When  the  piston  of  the  pump  is  pushed  dowoi,  water  is  forced 
through  the  aorta  D  along  the  tube  T  into  the  bottle,  and  flows  back 
again  into  the  left  auricle  by  the  tube  T'.  During  each  stroke  of  the 
pump  the  auriculo-ventricular  valve  is  seen  through  the  glass  disc 
inserted  into  C  to  close,  and  the  semilunar  valve  is  seen  through  the 
glass  in  D  to  open.  When  the  piston  is  raised,  the  semilunar  valve  is 
seen  to  be  closed  and  the  auriculo-ventricular  valve  to  be  opened. 
For  comparison,  a  human  heart  with  a  valvular  lesion  might  be  used. 

(2)  With  the  sheep's  or  dog's  heart  provided,  perform  the  following 
experiments : 

(a)  Open  the  pericardium  and  notice  how  it  is  reflected  around  the 
great  vessels  at  the  base  of  the  heart.  Distinguish  the  pulmonary 
artery,  the  aorta,  the  superior  and  inferior  venae  cavae,  and  the  pul- 
monary^ veins.  The  trachea  and  portions  of  the  lungs  may  also  be 
attached.     If  so,  remove  them  carefully  without  injuring  the  heart. 


PRACTICAL  EXERCISES  205 

{b)  Take  two  wide  glass  tubes,  drawn  slightly  into  a  neck  at  one  end. 
One  of  the  tubes  should  be  about  10  cm.  long,  and  the  other  about 
50  cm.  Tie  the  short  tube  A  firmly  by  its  neck  into  the  superior  vena 
cava,  the  long  tube  B  into  the  pulmonary  artery.  Ligature  the  inferior 
vena  cava.  Connect  A  by  a  small  piece  of  rubber  tubing  with  a  funnel 
supported  in  a  ring  on  a  stand.  Pour  water  into  the  funnel  till  the 
right  side  of  the  heart  is  full.  It  will  escape  from  the  left  azygos  vein, 
wliich  must  be  tied.  Put  on  any  additional  ligatures  that  may  be 
needed  to  render  the  heart  water-tight.  Support  B  in  the  vertical 
position  by  a  clamp.  Fill  the  funnel  with  water,  and  it  will  rise  in  B 
to  the  same  level  as  in  the  funnel.  Now  compress  the  right  ventricle 
with  the  hand,  and  the  water  will  rise  higher  m  B.  Relax  the  pressure 
and  notice  that  the  water  remains  at  the  higher  level  in  B,  being  pre- 
vented by  the  semilunar  valves  from  flowing  back  into  the  ventricle. 
By  alternately  compressing  the  ventricle  and  allowing  it  to  relax,  water 
can  be  pumped  into  B  till  it  escapes  from  its  upper  end,  and  if  this  is 
so  curved  that  the  water  falls  into  the  funnel,  a  '  circulation  '  which 
imitates  that  of  the  blood  tan  be  established.  Note  that  during  the 
pumping  the  sinuses  of  Valsalva,  behind  the  semilunar  valves  at  the 
origin  of  the  pulmonary  artery,  become  prominent. 

[c)  Take  out  B  and  tear  out  one  of  the  segments  of  the  semilunar 
valve.  Replace  B,  and  notice  that,  while  compression  of  the  ventricle 
has  the  same  effect  as  before,  the  water  no  longer  keeps  its  level  on 
relaxation,  but  regurgitates  into  the  ventricle.  This  illustrates  the 
condition  known  as  insufficiency  or  incompetence  of  the  valves.  But 
if  the  injury  is  not  too  extensive,  it  is  still  possible,  by  more  vigorously 
and  more  rapidly  compressing  the  heart,  to  pump  water  into  the  funnel. 
This  illustrates  the  establishment  of  compensation  in  cases  of  valvular 
lesion. 

[d)  Now  remove  both  tubes.  Tie  the  pulmonary  artery.  Cut  away 
the  greater  part  of  the  right  auricle.  Pour  water  into  the  auriculo- 
ventricular  orifice,  and  notice  that  the  segments  of  the  tricuspid  valve 
are  floated  up  so  as  to  close  the  orifice.  Invert  the  heart,  and  the 
ventricle  will  remain  full  of  water.  Open  the  right  ventricle  carefully, 
and  study  the  papillary  muscles  and  the  chordae  tcndincae,  noting  that 
the  latter  are  inserted  into  the  lower  surface  of  the  segments  of  the 
tricuspid  valve,  as  well  as  into  their  free  edges. 

[e)  Repeat  (6),  (c),  and  [d)  on  the  left  side  of  the  heart,  tying  tube  B 
into  the  aorta  as  far  from  the  heart  as  possible,  and  A  into  the  left  auricle. 

(/)  Separate  the  aorta  from  the  left  ventricle,  cutting  wide  of  its 
origin  so  as  not  to  injure  the  semilunar  valves,  and  tie  a  short  wide 
tube  into  its  distal  end.  Fill  the  tube  with  water,  and  notice  that  the 
valves  support  it.  Cut  open  the  aorta  just  between  two  adjacent  segments 
of  the  valve,  and  notice  the  pockets  behind  the  segments,  and  how  they 
are  related  to  each  other,  and  connected  to  the  wall  of  the  vessel. 

16.  Sounds  of  the  Heart. — (a)  In  a  fellow-student  notice  the  position 
of  the  cardiac  impulse,  the  chest  being  well  exposed.  Use  both  a 
binaural  and  a  single-tube  stethoscope.  Place  the  chest-piece  of  the 
stethoscope  over  the  impulse,  and  make  out  the  two  sounds  and  the 
pause.  (6)  With  the  hand  over  the  radial  or  brachial  artery,  try  to 
determine  whether  the  beat  of  tlie  pulse  is  felt  in  the  period  of  the 
sounds  or  of  the  pause,  (c)  Listen  with  tlie  stethoscope  over  the 
junction  of  the  second  right  costal  cartilage  with  the  sternum,  and 
compare  the  relative  intensity  of  the  two  sounds  as  heard  here  with 
their  relative  intensity  as  heard  over  the  cardiac  impulse. 

17.  Cardiogram. — Smoke  a  drum,  and  arrange  a  recording  tambour 
and  a  time-marker  beating  half  or  quarter  seconds  to  write  on  it  (Fig.  88, 


2o6  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

p  193).  Apply  the  button  of  a  cardiograph  (Fig.  27,  p.  00)  over  your 
own  cardiac  impulse,  and  lastenjt  round  the  body  by  the  bands  attached 
to  the  instrument.  Connect  the  cardiograph  by  an  indiarubber  tube 
with  a  recording  tambour  (Fig.  99).  Set  the  drum  off  at  a  fast  speed 
take  a  tracing,  and  vamish  it.  Compare  with  Fig.  28  (p.  91)  and  il 
the  tracing  is  sufficiently  typical,  as  is  often  not  the  case  with  human 
cardiograms,  measure  out  the  time -value  of  the  various  events  m  the 
cardiac  revolution. 


Fig.  99.— Marey's  Tambour. 

For  the  cardiograph,  a  small  glass  funnel,  or  thistle-tube,  the  stem 
of  which  is  connected  with  the  recording  tambour,  may  be  substituted, 
the  broad  end  of  the  funnel  being  pressed  over  the  apex-beat. 

18.  Sphygmographic  Tracings.— Attach  a  Marey's  sphygmograph 
(Fig.  37,  p.  165)  to  the  arm.  Fasten  a  smoked  paper  on  the  plate  D. 
Apply  the  pad  C  of  the  sphygmograph  to  the  wrist  over  the  point 

^  where  the  pulse  of  the  radial 

artery  can  be  most  distinctly 
felt.  Adjust  the  pressure  by 
moving  the  screw  G.  The 
writhig-point  of  the  lever  E 
will  rise  and  fall  with  every 
pulse-beat.  When  everything 
is  satisfactorily  arranged,  set 
off     the     clockwork     which 


100. — Dudgeon's  Sphygmograph. 


moves  the  plate  D,  and  a  pulse  tracing  will  be  obtained.  Study  the 
cl  hges  which  can  be  produced  in  the  pulse  curve — {a)  by  altering  the 
position  of  the  body  (sitting,  standing,  and  lying  down);  (/;)  by  exercise 
(Fig.  loi) ;  (c)  by  inhalation  of  2  drops  of  amyl  nitiite  poured  on  a  hand- 
kerchief by  the  demonstrator  (Fig.  10.^);  {d)  by  raising  the  arm  above 
the  head  and  letting  it  hang  at  the  side  ;  (e)  by  compression  of  the  brachial 
artery  at  the  bend  of  the  elbow;  (/)  by  altering  the  pressure  of  the  pad. 
Vamish  the  tracings  after  marking  on  them  the  conditions  under  which 
they  were  obtained. 

A  Dudgeon's  sphygmograph  (Fig.  100)  may  also  be  employed.      In 
this  the  clockwork  carries  the  strip  of  blackened  paper  along  beneath 


PRACTICAL  EXERCISES 


207 


Jv/v^^.^■/- 


i\-iLr^hA 


Fig.  loi. — Effect  of  Exercise  on  the 
Pulse  (Marey).  Upper  tracing, 
normal;  lower,  after  running. 


the  needle  which  records  tlic  movements  of  the  artery.  Or  a  small 
glass  funnel  or  thistle-tube  connected  with  a  recording  tambour  may 
be  pressed  over  the  carotid  artery.  The  lever  of  the  tambour  writes 
on  a  drum,  on  which  at  the  same  time  half  or  quarter  seconds  are 
marked  by  an  electro-magnetic  signal. 

19.  Venous  Pulse  Tracing  from  the 
Jugular  Vein. — Arrange  a  recording 
tambour  to  write  on  a  drum.  Con- 
nect the  tambour  with  the  stem  of  a 
small  glass  thistle-tube  or  funnel  (or 
with  a  small  metal  cup)  by  a  piece  of 
narrow  rubber  tubing,  and  apply  the 
cup-shaped  end  of  the  thistle-tube 
over  the  right  jugular  bulb  of  a 
fellow-student.  This  lies  about  i  inch 
external  to  the  right  stemo-clavicular 
articulation,  and  a  little  above  it.  The 
receiver  may  have  to  be  moved  about 
a  little  until  the  best  pulsation  is 
obtained.     The    '  patient  '  should  be 

lying  down,  the  shoulders  slightly  raised,  the  head  on  a  pillow  and  turned 
slightly  to  the  right,  in  order  to  relax  the  right  stemo-mastoid  muscle 
(Mackc^nzie). 

20.  Polygraph  Tracings.— Arrange  the  polygraph  over  the  radial 
artery,  as  with  an  ordinary  sphygmograph,  so  that  the  lever  will  record 
the  radial  pulse  when  the  strip  of  paper  is  set  moving.     If  the  instru- 

ment  has  only  one  tambour,  con- 
nect the  tambour  to  a  receiver 
or  thistle-tube  over  the  jugular 
bulb.  The  writing-point  of  the 
tambour  is  arranged  so  as  to  be 
immediately  below  the  writing- 
point  connected  with  the  radial. 
If  the  polygraph  is  provided 
with  clockwork  to  record  time, 
set  off  the  time-marker  writing 
fifths  of  a  second.  When  it  is 
Been  that  the  writing-points  are 
marking  properly,  start  the 
clockwork  which  moves  the 
strip  of  smoked  paper.  Repeat 
the  observation  with  the  tam- 
bour connected  with  the  apex- 
beat.  Letter  the  curves  as  far 
as  possible  as  in  Figs.  65  and 
66  (p.  149)  without  at  present 
attempting  their  exact  analysis. 
If  the  pol}-graph  has  two  taii'^ 
hours,  simultaneous  tracing  of  the  radial  pulse,  the  jugular  pulse,  and  the 
cardiac  impulse,  or  of  the  carotid  pulse,  the  jugular  pulse,  and  the  apex- 
beat,  may  be  taken,  and  other  combinations  as  well.  If  no  polygraph 
is  available,  a  drum  may  be  employed,  the  tracings  being  all  taken  with 
thistle-tubes  connected  with  recording  tambours.  The  levers  of  the 
tambours  must  be  arranged  to  write  on  the  drum  in  the  same  vertical 
straight  line, or,  without  making  the  adjustment  (.juite  exact,  vertical  lines 
of  reference  may  be  drawn  through  each  curve,  with  the  drum  at  rest, 
indicating  the  relative  positions  of  the  writing-points. 


Fig.  102. — Effect  of  Aniyl  Nitrite  on  the 
Pulse  (Marey).  Upper  tracing,  normal; 
lower,  after  inhalation  of  amvl  nitrite. 


2o8         THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

21.  Plethysmographic  Tracings, — Connect  the  vessel  D  (Fig.  36, 
p.  128),  directly  with  a  recording  tambour  by  the  tube  F.  omitting  for 
simplicity  the  recording  arrangement  in  the  figure.  Place  the  arm 
in  the  plethysmograph,  and  adjust  the  indiarubber  band  to  make 
a  watertight  connection.  Support  D  so  that  the  arm  rests  easily 
within  it,  and  fill  it  with  water  at  body  temperature.  No  water  must  get 
into  the  tambour,  and  it  is  well  to  insert  a  piece  of  glass  tubing  in  the 
connection  between  it  and  the  plethysmograph,  so  that  it  may  be  seen 
when  the  water  is  rising  too  high.  A  T-piece  with  a  short  piece  of 
rubber  tubing  on  the  stem  should  be  inserted  in  the  course  of  the  tube 
leading  to  the  tambour.  All  adjustments  are  made  with  the  T-piece 
open,  and  when  a  tracing  is  to  be  taken  the  short  rubber  tube  is  closed 
by  a  clip.  Arrange  a  time-marker  to  write  half  or  quarter  seconds 
(Fig.  88,  p.  193).  Adjust  the  writing-point  to  write  on  a  drum,  and 
close  the  upper  tubulure  C  with  a  cork.  The  quantity  of  blood  in  the 
ami  is  increased  with  every  systole  of  the  left  ventricle,  diminished  in 
diastole.  The  lever  will  therefore  rise  when  the  ventricle  contracts, 
and  sink  when  it  relaxes. 

(i)  Take  tracings  with  the  arm  {a)  horizontal,  (b)  hanging  down. 

(2)  With  the  arm  horizontal,  take  tracings  to  show  the  effect  {a)  of 
closing  and  opening  the  fist  inside  the  plethysmograph;*  (6)  of  apply- 
ing a  tight  bandage  round  the  arm  a  little  way  above  the  indiarubber 
band;  (c)  of  inhaling  2  drops  of  amyl  nitrite. 

Instead  of  the  arm  plethysmograph,  a  small  plethysmograph  to  hold 
a  finger  may  be  employed.  It  consists  of  a  glass  tube  drawn  out  at 
one  end.  The  wide  end  is  provided  with  a  rubber  collar.  The  narrow 
end  is  connected  by  a  small  rubber  tube  with  a  very  small  and  sensitive 
recording  tambour,  a  T-piece  being  inserted  on  the  connection  as  before. 
With  the  T-piece  closed  fill  the  tube  with  water.  Then,  holding  up  the 
wide  end  of  the  tube,  the  tip  of  the  finger  is  put  in  so  as  just  to  close 
the  tube.  The  T-piece  is  then  raised  and  opened,  and  the  finger  pushed 
in  as  far  as  it  will  go.  The  collar  must  fit  the  finger  so  as  to  form  a 
watertight  joint.  Now  get  the  proper  pressure  in  the  tambour  by 
blowing  into  the  T-piece,  and  close  the  clamp.  A  time-tracing  can  be 
taken  as  before. 

22.  Pulse-Rate. — (i)  Count  the  radial  pulse  for  a  minute  in  the 
sitting,  supine,  and  standing  positions.  Use  a  stop-watch,  setting  it 
off  on  a  pulse-beat  and  counting  the  next  beat  as  one.  Make  three 
observations  in  each  position. 

(2)  Count  the  pulse  in  a  person  sitting  at  rest,  and  then  again  in  the 
sitting  position  immediately  after  active  muscular  exertion.  Note  how 
long  it  takes  before  the  pulse-rate  comes  back  to  normal. 

(3)  Count  the  pulse  in  a  person  sitting  at  rest.  Repeat  the  observa- 
tion while  water  is  being  slowly  sipped,  and  note  any  change. 

(4)  With  one  hand  over  the  thorax  of  a  rabbit,  count  its  pulse.  Then 
notice  the  effect  {a)  of  suddenly  closing  its  nostrils,  (6)  of  bringing  a 
small  piece  of  cotton-wool  sprinkled  with  ammonia  or  chloroform  in 
front  of  the  nose  [reflex  inhibition  of  the  heart). 

23.  Blood-Pressure  Tracing. — [a]  Put  a  dog  under  morphine  (p.  63). 
Set  up  an  induction  machine  arranged  for  an  interrupted  current 
(Fig.  93,  p.  198).  Fill  the  U-shaped  manometer  tube  (if  tliis  has 
not  already  been  done)  with  clean  mercury  to  the  height  of  10  to 
12  cm.  in  each  limb.  If  the  float  tends  to  stick,  half  an  inch  of  oil 
may  be  put  above  the  mercury  in  the  di.stal  (straight)  limb  before 
putting  in  the  float.     But  where  the  mercury  is  clean  and  dry,  and  the 

*  Closing  the  fist  causes  a  lull  in  the  curve — i.e.,  a  diminution  in  the  volume 
ot  the  arm.     On  opening  the  hand,  the  curve  regains  its  level. 


PRACTICAL  EXERCISES  209 

size  of  the  float  properly  adjusted  to  that  of  the  tube,  this  is  not  neces- 
sary, and  is  to  be  avoided.  Then,  tilting  the  tube  carefully,  fill  the 
proximal  limb  {i.e.,  the  limb  which  is  to  be  connected  with  the  blood- 
vessel) with  a  saturated  solution  of  sodium  carbonate  or  a  half -saturated 
solution  of  magnesium  sulphate,  or,  what  is  better  for  most  purposes, 
a  2  per  cent,  solution  of  sodium  citrate.  This  is  easily  done  by  means 
of  a  pipette  furnished  with  a  long  point.  Now  attach  a  strong  rubber 
tube  to  the  proximal  end-  of  the  manometer,  and  fill  it  also  with  the 
solution.  All  air  must  be  got  out  of  the  manometer  and  its  connecting- 
tube.  Raise  the  end  of  the  rubber  tube  and  blow  into  it,  so  as  to  cause 
a  difference  of  about  10  cm.  in  the  height  of  the  mercury  in  the  two 
limbs  of  the  manometer,  and,  without  releasing  the  pressure,  clanip  the 
tube  with  a  pinchcock  or  screw  clamp  (Fig.  47,  p.  110). 

Now  smoke  a  drum,  and  arrange  the  writing-point  of  the  manometer- 
float  so  that  it  will  write  on  it.  Suspend  a  small  weight  by  a  piece  of 
silk  thread  from  a  support  attached  to  the  stand  of  the  drum,  so  that 
it  hangs  down  outside  of  the  writing-point  of  the  manometer-float  and 
always  keeps  it  in  contact  with  the  smoked  surface  without  undue 
friction.  Or  a  piece  of  glass  rod  drawn  out  to  a  fine  tliread  in  the 
blowpipe  flame  answers  very  well.  Below  the  writing-point  of  the 
float,  and  in  the  same  vertical  line  with  it,  adjust  the  writing-point 
of  a  time-marker  beating  seconds  (Fig.  88,  p.  193). 

Next  fasten  the  animal  on  a  holder,  back  down.  Give  ether  and 
insert  a  tracheal  cannula  (p.  100).  (The  tracheal  cannula  is  not  abso- 
lutely required  for  the  experiment,  but  it  is  convenient,  as  the  animal 
is  more  under  control,  and  artificial  respiration  can  be  begun  at  any 
moment,  should  this  be  necessary.)  Insert  a  glass  cannula,  armed 
with  a  short  piece  of  rubber  tubing,  into  the  central  (cardiac)  end  of 
the  carotid  artery  (p.  63).  Leaving  the  bulldog  forceps  on  the  artery, 
fill  the  cannula  and  tube  with  the  sodium  citrate  or  one  of  tlie  other 
solutions.  Slip  the  rubber  tube  over  a  short  glass  connecting-tube.  Fill 
this  also  with  the  solution,  and  connect  it  with  the  manometer-tube, 
seeing  that  both  are  quite  full  of  liquid,  so  that  no  air  may  be  enclosed. 

Where  a  permanent  working  place  is  provided  for  blood-pressure 
experiments  it  is  convenient  to  connect  the  cannula  and  manometer 
with  a  pressure-bottle  containing  the  sodium  citrate  solution,  and  to 
use  a  three-way  cannula  for  the  bloodvessels  (Fig.  103).  The  cannula 
has  a  bulbous  enlargement,  which  hinders  clotting.  The  end  of  the 
cannula  is  connected  with  the  tube  from  the  pressure -bottle,  which  is 
closed  by  a  clip,  and  the  side-tube  is  connected  with  one  limb,  E,  of 
the  manometer  shown  in  Fig.  104.  E  is  itself  provided  with  a  side- 
tube,  F,  armed  with  a  short  piece  of  rubber  tubing.  The  cannula  does 
not  require  to  be  filled  with  liquid  before  being  inserted  into  the  artery. 
By  opening  F  and  releasing  the  clip  on  the  tube  from  the  pressure- 
bottle  the  cannula  and  the  tube  connecting  it  with  the  manometer  can 
be  filled,  and  any  blood-clots  can  be  easily  washed  out  in  the  course  of 
an  experiment.  Before  the  bulldog  forceps  is  taken  off  the  artery  to 
obtain  a  blood-pressure  tracing,  F  must  be  closed,  and  the  clip  on' the 
tube  from  the  pressure-bottle  opened.  The  bottle  is  attached  to  a 
strong  cord  passing  over  a  pulley,  by  which  it  is  raised  to  a  height 
sutficient  to  balance  approximately  the  pressure  in  the  artery.  The 
tube  to  the  pressure-bottle  is  then  clipped.  If  no  manometer  with 
side-tube  is  available,  a  T-piece  can  be  inserted  in  the  connection 
between  the  cannula  and  the  manometer,  and  the  cannula  can  be 
washed  out  thn-ugh  this. 

Now  take  the  bulldog  forceps  off  the  artery,  and  allow  the  drum  to 
revolve  at  slow  speed.     The  writing-point  of  the  manometer-float  will 

14 


THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 


trace  a  curve  showing  an  elevation   for   each 
waves  due  to  the  movements  of  respiration. 

(p)  Isolate  the  vago-sympathetic  nerve  Q 
in  the  neck.  Ligature  doubly,  and  cut 
between  the  ligatures.  Stimulate  the  peri- 
pheral (lower)  end ;  the  heart  will  be  slowed 
or  stopped,  and  the  blood-pressure  will  fall. 
Stimulate  the  central  (upper)  end;  there 
may  be  inhibition  of  the  heart  or  accelera- 
tion, and  the  pressure  may  fall  or  rise 
(p.  168). 

(c)  Expose  and  divide  the  other  vago- 
sympathetic while  a  tracing  is  being  taken. 
Again  stimulate  the  central  end  of  the 
nerve  and  observe  whether  there  is  any 
effect. 

{d)  Expose  the  sciatic  nerve  in  one  leg, 
as  follows:  The  leg  having  been  loosened 
from  the  holder,  the  foot  is  seized  by  one 
hand  and  lifted  straight  up,  so  as  to  put 


heart-beat,  and  longer 


Fig.  103. — Three-way  Cannula. 

the  skin  of  the  thigh  on  the  stretch.  An 
incision  is  now  made  in  the  middle  line  on 
the  posterior  aspect  of  the  thigh,  through 
the  skin  and  subcutaneous  tissue.  The 
muscles  are  separated  in  the  line  of  the 
incision  with  the  fingers,  and  the  sciatic 
nerve  comes  into  view  lying  deeply  be- 
tween them.  Place  a  double  ligature  on  it, 
and  divide  between  the  ligatures.  Stimu- 
late the  upper  (central  end) ;  the  blood- 
pressure  probably  rises,  and  the  heart  may 
be  accelerated.  Stimulate  the  peripheral 
end  of  the  nerve ;  there  is  little  change  in 
the  blood-pressure  and  none  in  the  rate  of 
the  heart. 

{e)  Note,  incidentally,  that  stimulation 
of  the  central  end  of  the  sciatic  or  the  upper 
(cephalic)    end   of   the   vago-sympathetic 
may  cause  increase  in  the  rate  and  depth  of  the  respiratory  movements. 
Dilatation  of  the  pupil  is  also  caused  by  stimulation  of  the  upper  end  of 


Fig.  104.  —  Manometer  with 
Side-tube  (Guthrie).  A,  float ; 
B,  collar  through  which  the 
wire  C  of  the  float  moves;  D, 
vertical  wire  fixed  to  mano- 
meter-holder, which  keeps  the 
writing-point  on  the  drum; 
E,  limb  of  manometer  con- 
nected with  cannula,  with  its 
side-piece.  F. 


PRACTICAL  EXERCISES  21, 

ttt'^SlTXlri:'"  ''""^'  ''^  sympathetic  (pupnio-dilator)  f.br.s 

+1.^0  ^^""'i"  s-timulate  the  peripheral  end  of  one  vagus,  or  of  both  at 
the  same  time,  while  a  tracmg  is  being  taken,  and  see  how  Jong  t  ts 
possible  to  keep  the  heart  from  beating"  -Sometimes,  but  rlrely  in  the 
dog  inhibition  can  be  kept  up  so  long  that  the  animal  dies.       ^ 

{g)  Close  the  tracheal  cannula  so  that  air  can  no  longer  enter  the 

ungs.      In  a  very  short  time  the  blood-pressure  curve  begins  to  rise 

(rise  of  asphyxia).     After  some  minutes  the  pressure  fall     and  finaHv 

when  the  circulation   has  stopped   completely  and   the   pressure    has 

pTe^:^-e  :r±?'  yirougHout  the   whol?   vas'cular  sysfe^a    "s.^^3 

frordcT  foT't-;f  ^r  ""''•  ("'"^"y  ^b°"^  ^«  ^^-  Hg)  is  indicated, 
in  order  to  get  the  true  zero  pressure,  disconnect  the  arterial  cannula 


Fig.  105  -Blood.P.essure  Tracmg  from  a  Dog:  Stimulation  of  Central  and  Peripheral 
Lnds  of  Vagus.  The  other  vagus  was  intact.  Stimulation  of  the  peripheral  end 
caused  stoppage  of  the  heart  and  a  marked  fall  of  pressure.     Stimulafion  of  the 

of 'JLe'L'Lt  ''  '  ^''''  "''  °^  ^''''"'''  '''''''  P^^^^P^'  ^  ^^'g^^  accelerat  on 


from  the  manometer,  and  allow  the  writing-point  to  trace  a  horizontal 
straight  hue  (line  of  zero  pressure)  on  the  drum  (Figs.  84  and  8^) 

24.  Estimation  of  the  Arterial  Blood-Pressure  in  Man.— Use  the  Rivi 
Rocci  apparatus,  as  described  on  p.  1 1 3.  Begin  with  the  subiect  in  tlt 
sittmg  position^  The  observer's  left  hand  may  be  used  forTaVat  ^ 
the  pulse,  and  the  right  for  working  the  bulb.'  Employ  the  ausxulta" 
tory  method  as  well  as  palpation,  and  determine  the  systolic  and  d  as- 
tohc  pressures.  Repeat  tlie  observations  with  the  person  standinrup 
fcbod^rfssuT-     '"^^^^^S^^<^  ^''^  ^«'^-t  ^'  "^"«^-"lar  exercise  on%h? 

?^i  J/"^  Influence  of  the  Position  of  the  Body  on  the  Blood-Pressure. 

-Inject  into  the  rectum  of  a  dog  3  to  4  grm.  of  chloral  hydrate  dis 
solved  in  a  little  water.     See  chat  it  does  not  run  out  again  immediately 


212  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

after  injection.  In  ten  minutes  anaesthetize  the  animal  fully  with  a 
mixture  of  equal  parts  of  alcohol,  chloroform,  and  ether  (one  of  the 
so-called  A.C.E.  mixtures),  or  with  chloroform,  and  tie  it  very  securely, 
back  downward,  on  a  board,  which  can  be  rotated  around  a  horizontal 
axis,  corresponding  in  position  to  the  point  at  which  the  cannula  is  to 
be  inserted.*  Set  up  a  drum  and  manometer  as  in  23  (p.  208),  but  with 
a  rubber  connecting-tube  of  such  length  as  will  allow  free  rotation  of 
the  board.  Put  a  cannula  in  the  trachea.  Insert  a  cannula  into  the 
central  end  of  the  carotid  artery  at  a  point  immediately  above  the  axis 
of  rotation  of  the  board,  and  connect  it  with  the  manometer. 

(a)  Take  a  blood-pressure  tracing  wdth  the  board  horizontal. 

(b)  Whilst  the  tracing  is  being  taken,  rotate  the  board  so  tliat  the 
position  of  the  animal  becomes  vertical,  with  the  feet  down.  Mark 
on  the  tracing  the  moment  when  the  change  of  position  takes  place. 
The  pressure  falls.  Replace  the  dog  in  the  horizontal  position.  The 
manometer  regains  its  former  level.  Now  rotate  the  board,  till  the 
animal  is  again  vertical,  but  with  feet  up  and  head  down,  and  observe 
the  effect  on  the  blood-pressure.  The  respirator^'  variations  in  the 
pressure  are  usually  greater  with  feet  down  than  with  head  down. 
Notice  in  both  cases  whether  there  is  any  change  in  the  rate  of  the  heart. 

(c)  Take  the  board  off  the  stands,  lay  it  on  a  table,  expose  the  femoral 
artery,  and  insert  a  cannula  into  it.  Shift  the  axis  so  that  it  now  lies 
below  this  cannula.  Replace  the  board  on  the  stands,  and  repeat  (a) 
and  {b).  The  fall  of  pressure  will  now  take  place  in  the  head-down 
position. t  In  the  feet-dowTi  position  (with  the  cannula  in  the  femoral 
artery)  a  rise  of  pressure  in  general  takes  place.  But  sometimes  this 
is  very  small,  and  lasts  only  a  few  seconds,  being  succeeded  by  a  fall, 
during  which  the  heart-beats  on  the  tracing  are  much  weaker  than 
before,  since  enough  blood  is  not  reaching  the  heart  to  enable  it  to 
maintain  the  pressure.  In  the  feet-down  position  see  whether  the 
corneal  reflex  can  be  got.  If  not,  as  is  likely,  turn  the  animal  into  the 
head-dowTi  position.  The  reflex  may  now  soon  be  obtained,  and  it 
may  again  disappear  on  putting  the  animal  in  the  feet-down  position. 
If  the  chloroform  anaesthesia  is  light  the  reflex  may  not  be  abolished 
in  the  feet-down  position,  although  strong  respiratory  movements  may 
occur,  owing  to  anaemia  of  the  medulla  oblongata. 

26.  Effects  of  Haemorrhage  and  Transfusion  on  the  Blood-Pressure. 
— Anaesthetize  a  dog  with  morphine  and  ether,  and  insert  a  cannula 
into  the  trachea.  Put  a  cannula  into  the  central  end  of  the  carotid 
artery  and  another  into  the  central  end  of  the  femoral  artery.  Then 
insert  a  cannula,  which  should  have  a  piece  of  indiarubber  tubing  2  to 
3  inches  in  length  on  its  wide  end,  into  the  central  end  of  the  femoral 
vein  on  the  opposite  side.     In  doing  this  more  care  is  necessary  than 

*  A  simple  arrangement  for  this  purpose  is  a  board  with  a  number  of  staples 
fastened  in  pairs  into  its  lower  surface,  so  that  an  iron  rod  can  be  pushed 
through  any  pair,  and  form  a  horizontal  axis  at  right  angles  to  the  length  of 
the  board.  The  dog  having  been  tied  down,  the  rod  is  pushed  through  the 
pair  of  staples  corresponding  to  the  position  of  the  cannula  in  the  artery  that 
is  to  be  connected  with  the  manometer.  The  projecting  ends  of  the  rod  rest 
in  two  ordinary  clamp-holders,  fastened  at  a  convenient  height  on  two  strong 
stands,  whose  bases  are  clamped  to  the  end  of  a  table.  The  other  end  of  the 
board  is  supported  by  a  piece  of  wood  that  rests  on  the  floor,  £ind  can  be  re- 
moved when  the  board  is  to  be  rotated. 

f  In  16  dogs  the  fall  of  pressure  in  the  carotid  in  the  feet-down  position 
varied  from  12  to  100  mm.  of  mercury;  average  fall,  44-4  mm.  In  12  out  of 
the  16  animals  the  rise  of  pressure  in  the  head-down  position  varietl  from 
2  to  36  mm. ;  in  i  there  was  no  change;  in  3  there  was  a  fall  of  5  to  24  mm. 


PRACTICAL  EXERCISES  213 

in  putting  a  cannula  into  an  artery.  Feel  for  the  femoral  artery,  cut 
down  over  it,  and  with  forceps  or  a  blunt  needle  separate  the  femoral 
vein  from  it  for  about  an  inch.  Pass  two  ligatures  imder  the  vein,  and 
tie  a  loose  loop  on  each.  Put  a  pair  of  bulldog  forceps  on  the  vein 
between  the  ligatures  and  the  heart.  Now  tie  the  lower  (distal)  liga- 
ture, and  cut  one  end  short.  The  piece  of  vein  between  it  and  the 
bulldog  forceps  is  thus  distended  with  blood,  and  this  facilitates  the 
next  step.  With  fine-pointed  scissors  make  a  snip  in  the  wall  of  the 
vein.  The  cannula  is  now  pushed  tlirough  the  slit  in  the  vein,  and 
the  upper  ligature  tied  firmly  round  its  neck.  By  the  aid  of  a  pipette, 
made  by  drawing  a  piece  of  glass  tubing  out  to  a  long  point,  the  cannula 
and  rubber  tube  are  then  completely  filled  with  09  per  cent,  salt 
solution.  Be  sure  to  pass  the  point  of  the  pipette  right  down  to  the 
point  of  the  cannula,  so  as  to  dislodge  any  bubble  of  air  that  may  tend 
to  cling  there.  Then,  holding  up  the  open  end  of  the  rubber  tube, 
close  it,  without  allowing  any  air  to  enter,  by  means  of  a  screw  clamp 
or  bulldog  forceps,  or  a  small  piece  of  glass  rod.  Connect  the  cannula 
in  the  carotid  with  a  manometer,  arranged  to  write  on  a  drum  as  in 
experiment  23  (p.  208).  Take  the  bulldog  oft  the  carotid,  and  measure 
the  difference  in  the  level  of  the  mercury  in  the  two  limbs  of  the  man- 
ometer with  a  millimetre  scale. 

(i)  [a)  While  a  tracing  is  being  taken,  draw  off  about  10  c.c.  of  blood 
from  the  femoral  artery,  and  observe  whether  there  is  any  effect  on 
the  tracing.  Mark  on  the  tracing  the  moment  when  the  removal  of 
the  blood  begins  and  ends. 

[b)  Repeat  (a),  but  rim  off  about  100  c.c*  of  blood,  and  let  this  be 
immediately  defibrinated.  Then  draw  off  portions  of  100  c.c*  at  short 
intervals  until  a  distinct  fall  of  blood-pressure  has  been  produced.  All 
the  samples  of  blood  should  be  defibrinated  and  strained  through 
cheese-cloth. 

(2)  (a)  Now,  while  a  tracing  is  being  taken,  inject  the  whole  of  the 
defibrinated  blood  slowly  through  the  cannula  in  the  femoral  vein  by 
means  of  a  funnel  supported  by  a  stand  at  such  a  height  that  the  blood 
runs  in  easily.  A  pinchcock  should  be  put  on  the  tube  connecting  the 
funnel  and  the  cannula,  and  this  should  be  closed  before  the  funnel  is 
quite  empty,  so  as  to  obviate  any  risk  of  air  getting  into  the  vein.  Of 
course,  the  cannula  and  connecting-tubes  must  all  be  freed  from  air 
before  injection  is  begun.  Again  measure  the  difference  in  the  level 
of  the  mercury  and  compare  the  pressure  with  that  observed  before 
the  first  haemorrhage. 

(6)  Inject  into  the  vein,  while  a  tracing  is  being  obtained,  about 
100  c.c*  of  og  per  cent,  salt  solution  heated  to  .40°  C,  and  go  on 
injecting  portions  of  100  c.c.  until  a  distinct  rise  of  pressure  has  taken 
place,  keeping  a  record  of  the  total  amount  injected,  and  marking  the 
time  of  each  injection  on  the  curve. 

(c)  After  an  interval  of  thirty  minutes,  again  measure  the  height  of 
the  mercury  in  the  manometer.  Then  bleed  the  dog  to  death  while  a 
tracing  is  being  recorded. 

27.  The  Influence  of  Proteoses  (and  Peptones)  on  the  Blood-Pressure. 
— Set  up  the  apparatus  for  taking  a  blood-pressure  tracing  as  in  experi- 
ment 23  (p.  208),  but  omit  the  induction-coil.  Weigh  a  dog.  Weigh 
out  a  quantity  of  Witte's  peptone  equivalent  to  05  grm.  for  every  kilo 
of  body-weight.  Dissolve  the  peptone  in  about  ten  times  its  weight 
of  09  per  cent,  salt  solution.  Anaesthetize  the  dog  with  morphine  and 
ether  or  A.C.E.  mixture.  Insert  a  cannula  into  the  trachea.  Put 
cannulae  into  the  central  end  of  one  carotid  and  of  one  femoral  vein 

*  200  c.c.  for  a  large  dog. 


214  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

(p.  212).  Connect  the  carotid  with  the  manometer,  and  the  femoral 
vein  with  a  burette  or  large  syringe  containing  the  peptone  solution. 
Take  care  that  the  connecting-tube  and  cannula  are  free  from  air. 
Now  commence  to  take  a  blood-pressure  tracing,  and  while  it  is  going 
on  inject  the  peptone  solution.  The  pressure  falls  owing  largely  to 
a  dilatation  of  the  small  arteries  through  the  direct  action  of  the  pep- 
tone on  their  muscular  tissue  or  on  the  endings  of  the  vaso-motor  nerves.* 
28.  Eftect  of  Suprarenal  Extract  on  the  Blood-Pressure. — Make  the 
arrangements  for  a  blood-pressure  tracing  from  a  dog  as  in  23  (p.  208). 
Put  a  cannula  in  the  carotid  and  another  in  the  femoral  vein  or  one  of 
its  branches  (p.  212).  Expose  both  vagi  in  the  neck,  and  pass  threads 
loosely  under  them.  Connect  the  carotid  with  the  manometer  and 
take  a  tracing.  Then,  while  the  tracing  is  continued,  inject  slowly 
into  the  femoral  vein  an  amount  of  watery  extract  corresponding  to 
about  o'2  grm.  of  suprarenal,  or,  what  is  more  convenient,  a  few  c.c. 
of  a  solution  of  adrenalin  chloride  of  the  strength  of  i  to  50,000  in 
o"9  per  cent.r  sodiumrchloride  solution,  the  dose  depending,  of  course, 
on   the  size  of  the  animal.     The  blood-pressure  risesf  owing  to  con- 


Fig.   106. — Effect  of  Injection  of  Peptone  on  the  Blood-Pressure  in  a  Dog. 
(To  be  read  from  right  to  left.) 

striction  of  the  arterioles  by  direct  excitation  of  the  junction  between 
their  vaso-constrictor  nerves  and  their  muscular  tissue.  The  heart  is 
slowed,  but  its  beat  is  strengthened.  At  once  cut  both  vagi  while  a 
tracing  is  being  taken;  the  blood-pressure  rises  still  more  (p.  638). 
The  rise  of  pressure  is  sometimes  so  great  that  to  prevent  the  mercury 
from  being  forced  out  of  the  manometer  the  tube  must  be  clipped. 
The  rise  is  not  long  maintained,  but  a  second  injection  causes  a  renewed 
increase  of  pressure. 

29.  Action  of  Epinephrin  (Adrenalin)  on  Artery  Rings. — The  experi- 
ment (8)  described  on  p.  66  in  connection  with  the  constrictor  action 
of  serum  may  equally  well  be  performed  here. 

*  In  12  dogs  the  blood-pressure  always  fell,  the  amount  of  the  fall  varying 
from  81  to  21  mm.  of  mercury  (average,  60  mm.).  It  sometimes  returned  to 
normal  in  twenty  to  thirty  minutes,  but  usually  required  a  longer  time.  In 
some  dogs,  after  the  injection  of  the  whole  of  this  amount  of  peptone,  death 
■  occurs  before  there  has  been  any  considerable  recovery  of  the  pressure. 

■f  The  amount  of  the  initial  rise  of  pressure  is  very  variable,  since  the  slow- 
ing of  the  heart  tends  to  diminish  the  pressure,  while  the  constriction  of  the 
arterioles  tends  to  increase  it.  Thus,  in  one  experiment  the  increase  of  pres- 
sure on  injection  of  the  extract  was  only  6  mm.  of  mercury,  while  in  another 
it  was  56  mm.  On  section  of  the  vagi  in  this  second  experiment,  there  was 
an  additional  rise  of  64  mm.,  and  after  a  second  injection  a  further  rise  of 
70  mm.,  making  an  increase  of  190  mm.  in  all  above  the  original  pressure. 


PRACTICAL  EXERCISES  215 

30.  Section  and  Stimulation  of  the  Cervical  Sympathetic  in  the  Rabbit. 
— Set  up  an  induction-coil  arranged  for  an  interrupted  current  (Fig.  93, 
p.  ig8),  and  connect  it  through  a  short-circuiting  key  with  electrodes. 
The  preparations  necessary  for  an  operation  with  antiseptic  precautions 
arc  supposed  to  have  been  previously  made — the  instruments,  sponges, 
and  ligatures  boiled  in  water;  the  instruments  then  immersed  in  a 
5  per  cent,  solution  of  carbolic  acid,  the  sponges  and  ligatures  in  cor- 
rosive sublimate  solution  (o'l  per  cent.).  Instead  of  sponges  swabs  cf 
sterile  gauze  or  cotton  may  be  employed,  and  until  the  observations  on 
the  nerve  have  been  made  it  is  better  to  use  sterile  og  per  cent,  salt 
solution  for  such  slight  sponging  as  the  wound  may  require  rather  than 
the  antiseptic  solutions.  The  hands  are  to  be  thoroughly  washed, 
with  diligent  use  of  the  nail-brush,  in  soap  and  water  before  the  cutting 
operation  begins,  and  then  .soaked  successively  in  alcohol  and  in  the 
corrosive  sublimate  solution. 

Fasten  the  rabbit  on  a  holder,  back  downwards,  as  in  Fig.  61.  Keep 
the  animal  warm  by  covering  it  with  a  cloth,  and  do  not  handle  or  wet 
its  ears.  Clip  off  the  hair  on  the  anterior  surface  of  the  neck.  Remove 
loose  hairs  with  a  wet  sponge,  shave  the  neck,  and  wash  it  thoroughly, 
first  with  .soap  and  water,  and  then  with  corrosive  sublimate.  Give 
ether.  Make  a  longitudinal  incision  in  the  middle  line  over  the  trachea, 
beginning  a  little  below  the  thyroid  cartilage  and  extending  downwards 
for  an  inch  and  a  half.  Feel  for  the  carotid  artery,  expose,  and  raise 
it  up.  Two  nerves  will  now  be  seen  coursing  beside  the  artery.  The 
larger  is  the  vagus,  the  smaller  the  sympathetic.  A  third  and  much 
finer  nerve  (the  depressor,  or  superior  cardiac  branch  of  the  vagus) 
may  also  be  seen  in  the  same  position,  but  the  student  should  neglect 
this  for  the  present.  Pass  a  ligature  under  the  sympathetic,  and  tie 
it,  the  ear  being  held  up  to  the  light  while  this  is  being  done,  so  that 
its  vessels  may  be  clearly  seen.  A  transient  constriction  of  the  arteries 
may  be  seen  at  the  moment  when  the  nerve  is  ligatured.  This  is  due 
to  stimulation  of  the  vaso-constrictor  fibres.  Then  follows  a  marked 
dilatation  of  the  bloodvessels,  due  to  paralysis  of  these  fibres.  The 
car  is  flushed  and  hot.  Note  also  that  the  pupil  is  probably  narrower 
on  the  side  on  which  the  nerve  has  been  tied.  On  stimulation  of  the 
upper  (cephalic)  end  of  the  sympathetic  with  the  electrodes,  the  vessels 
are  markedly  constricted,  the  ear  becomes  pale  and  cold,  and  the  pupil 
dilates.  Cut  the  nerve  above  and  below  the  ligature,  and  take  out  the 
ligature.  Wash  the  wound  thoroughly  with  corrosive  sublimate,  then 
with  sterile  (boiled)  water,  and  close  it,  the  muscles  being  first  brought 
together  by  a  row  of  interrupted  sutures  and  then  the  skin  by  another 
row.  Since  it  is  difiicult  to  thoroughly  disinfect  the  hair-follicles,  and 
a  suture  passed  through  a  septic  follicle  is  apt  to  give  rise  to  suppura- 
tion, subcutaneous  stitches — i.e.,  stitches  passed  by  a  curved  needle 
through  the  deep  layer  of  the  skin  without  coming  through  to  the 
surface — may  be  employed.  The  wound  is  to  be  protected  by  a  coating 
of  collodion.  No  other  dressing  is  required.  The  animal  is  now 
removed  from  the  holder  and  put  back  to  its  hutch.  The  student  must 
examine  it  at  least  once  a  day  for  the  next  week,  and  study  the  difi'er- 
ences  between  the  two  ears  (]).  173)  and  the  two  pupils. 

31.  Determination  of  the  Circulation-Time. — (a)  Begm  with  an  arti- 
ficial scheme  (Fig.  107).  Fill  the  syringe  with  a  o'i  per  cent,  solution 
of  methylene  blue.  Allow  the  water  to'flow  from  the  bottle  by  loosen- 
ing the  clamp.  Inject  a  definite  quantity  of  the  mcthylenc-blue  solu- 
tion, and  with  a  stop-watch  observe  how  long  it  takes  to  pass  from 
the  point  of  injection  to  the  end  of  the  glass  tube  filled  with  beads. 
Make  ten  readings  of  this  kind,  and  take  the  mean.     Then  raise  the 


2i6  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

bottle  so  as  to  increase  the  rate  of  flow  of  the  water,  and  repeat  the 
observations.  The  '  circulation-time  '  will  be  found  to  be  diminished. 
This  corresponds  to  an  increase  of  blood -pressure  due  to  increased 
activity  of  the  heart,  without  change  in  the  calibre  of  the  bloodvessels. 
Next,  leaving  the  bottle  in  its  present  position,  diminish  the  outflow 
by  tightening  the  clamp;  the  circulation-time  will  be  increased.  This 
corresponds  to  an  increase  of  blood-pressure  due  to  diminution  in  the 
calibre  of  the  small  arteries. 

{h)  Fill  the  syringe*  with  methylene -blue  solution  (o-2  per  cent,  in 
0-9  per  cent,  salt  solution),  as  in  (<?).  Keep  the  solution  warmed  to 
40°  C.  by  immersing  the  small  beaker  containing  it  in  a  water-bath,  or 


Fig.  107. — Artificial  Scheme  to  illustrate  a  Method  of  measuring  the  Circulation- 
Time.  B,  bottle  containing  water,  the  rate  of  outflow  of  which  is  regulated  by 
screw -clamp  a  ;  S,  syringe  filled  with  methylene -blue  solution,  connected  with 
T-piece  A;  M,  beaker  containing  methylene-blue  solution;  b,  c,  screw-clamps; 
C,  T-piece,  inserted  in  the  course  of  the  flexible  tube  E,  and  connected  with  the 
glass  tube  T,  which  is  filled  with  beads;  F,  outflow  tube.  The  clamp 'c  having 
been  closed  and  b  opened,  the  syringe  is  filled  with  the  methylene-blue  solution; 
b  is  then  closed,  c  opened,  and  a  definite  quantity  of  the  solution  injected  into  the 
system.  The  time  from  the  beginning  of  injection  till  the  appearance  of  the  blue 
at  G  is  measured  with  the  stop-watch. 

heating  it  over  a  bunsen  with  a  small  flame.  Weigh  a  rabbit  or  cat. 
In  the  case  of  the  rabbit,  inject  ^  grm.  chloral  hydrate  into  the  rectum, 
and  later  on  give  ether  if  necessary.  If  a  cat,  give  ether  alone.  Fasten 
it  on  a  holder,  back  downwards  (Fig.  61,  p.  136).  Cover  it  with  a 
towel  to  keep  it  warm.  Clip  off  the  hair  on  the  front  of  the  neck,  and 
make  an  incision  i^  inches  long  in  the  middle  line,  beginning  a  little 

*  A  burette,  sloped  so  as  to  make  a  small  angle  with  the  horizontal,  may 
be  substituted  for  the  syringe.  The  burette  is  supported  on  a  stand  at  such 
a  height  (say  10-15  cm.  above  the  level  of  the  cannula)  that  the  methylene- 
blue  solution  runs  without  great  force  into  the  jugular.  'J"hc  danger  of  pro- 
ducing an  abnormal  result  by  suddenly  raising  the  pressure  in  the  right  side 
of  the  lieart  is  thus  avoided. 


PRACTICAL  EXERCISES  217 

way  below  the  cricoid  cartilage.  Reflect  the  skin  and  isolate  the 
external  jugular  vein,  which  is  quite  superficial.  Carefully  separate 
about  f  inch  of  the  vein  from  the  surrounding  tissue,  and  pass  two 
ligatures  under  it,  but  do  not  tie  them.  Compress  the  vein  with  a  pair 
of  bulldog  forceps  between  the  heart  and  the  ligatures.  Now  tie  the 
uppermost  of  the  two  ligatures  (that  nex±  the  head),  but  only  put  a 
single  loose  loop  on  the  other.  The  piece  of  vein  between  the  upper 
ligature  and  the  bulldog  is  now  distended  with  blood.  With  fine- 
pointed  scissors  make  a  small  slit  in  the  vein,  taking  great  care  not  to 
divide  it  completely,  insert  the  cannula,  and  tie  the  loose  ligature  firmly 
over  its  neck.  Fill  the  cannula  and  the  small  piece  of  rubber  tubing 
attached  to  it  with  og  per  cent,  salt  solution  by  means  of  a  pipette 
with  a  long  point.  Expose  the  carotid  on  the  other  side,  isolate  it  for 
f  inch,  clear  it  carefully  from  its  sheath,  slip  under  it  a  strip  of  thin 
sheet  indiarubber,  and  between  this  and  the  artery  a  little  piece  of  white 
glazed  paper.  Connect  the  cannula  in  the  jugular  with  the  T-piece 
attached  to  the  syringe.  Care  must  be  taken  that  no  air  remains  in 
the  cannula  or  its  connccting-tubc,  as  a  rabbit  not  unfrequently  dies 
instantaneously  when  a  bubble  of  air  is  injected  into  the  right  heart, 
although  a  considerable  quantity  of  air  can  generally  be  injected  into 
the  jugular  of  a  dog  without  killing  it. 

Now  take  off  the  bulldog  from  the  vein,  and  make  a  series  of  observa- 
tions on  the  pulmonary  circulation-time.  The  animal  must  be  so 
placed  that  a  good  light  falls  on  the  carotid.  If  necessary,  the  light 
of  a  gas-flame  may  be  concentrated  on  it  by  a  lens.  The  student  holds 
the  stop-watch  in  one  hand,  and  injects  a  measured  quantity  of  the 
methylcne-blue  solution  with  the  other.  Uniformity  in  the  quantity 
injected  is  secured  by  fastening  on  the  piston  of  the  syringe  a  screw- 
clamp,  which  stops  the  piston  at  the  desired  point.  The  obserx'ation 
consists  in  setting  off  the  watch  at  the  moment  when  injection  begins 
and  stopping  it  when  the  blue  appears  in  the  carotid.  After  each 
injection  the  screw-clamp  or  pinchcock  on  the  tube  connected  with  the 
cannula  must  be  tightened,  the  other  opened,  and  the  syringe  refilled. 
Great  care  must  be  taken  never  to  open  the  two  clamps  at  the  same 
time,  as  in  that  case  blood  may  regurgitate  through  the  jugular  and 
fill  the  syringe,  or  methjdene  blue  may  be  sucked  into  the  circulation. 
As  many  observations  as  possible  should  be  taken,  and  the  mean 
determined.  The  circulation-time  observed  is  approximately  that  of 
the  lesser  circulation,  the  time  taken  by  the  blood  to  pass  from  the 
left  ventricle  to  the  carotid  being  negligible  for  the  purposes  of  the 
student. 

The  specific  gravity  of  the  blood  may  also  be  tested  at  the  beginning 
and  end  of  the  experiment  by  Hammerschlag's  method  (p.  62).  If 
a  large  number  of  injections  have  been  made  in  quick  succession,  the 
specific  gravity  will  be  less  than  normal ;  but  if  a  considerable  interval 
has  been  allowed  to  elapse  after  the  last  injection,  little  or  no  differ- 
ence may  be  found,  as  the  surplus  liquid  readily  passes  out  of  the 
bloodvessels. 

A^ec>-o/>sy.— Observe  particularly  the  state  of  the  lungs,  whether  the 
bladder  is  distended  or  not,  and  whether  any  of  the  serous  cavities  or 
the  intestines  contain  much  liquid;  so  as  to  determine,  if  possible,  by 
what  channel  the  water  inj«>cted  into  the  blood  may  have  been  elimin- 
ated. Study  the  distribution  of  the  methylene  blue  in  such  organ?  as 
the  kidneys  and  the  muscles  immediately  after  death,  and  notice  that 
the  blue  colour  becomes  more  pronounced  after  exposure  for  a  time  to 
the  air.  ISIake  a  longitudinal  section  through  a  kidney,  and  observe 
that  the  pigment  is  found  especially  in  the  cortex  and  around  the 


2i8  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

pelvis  at  the  apices  of  the  pyramids,  or  it  may  be  only  in  the  cortex. 
The  urine  is  greenish.  If  some  methylene  blue  has  been  injected  after 
the  heart  ceased  to  beat,  the  bloodvessels,  particularly  in  the  mesentery, 
may  be  beautifully  mapped  out  by  the  pigment.  This  is  not  the 
case  if  the  last  injection  took  place  before  death,  since  the  methylene 
blue  is  rapidly  reduced  by  living  tissues  to  a  colourless  substance, 
leuco-methylene  blue. 

32.  Measurement  of  the  Blood-Flow  in  the  Hands. — Arrange  the 
calorimeters  as  in  Fig.  108.  The  thermometers  in  the  calorimeters 
should  be  graduated  in  tenths  of  a  degree,  so  that  by  means  of  the  small 
lenses  or  '  readers  '  which  slide  on  the  stems  hundredths  of  a  degree 
can  be  estimated.  Where  it  is  desirable  that  a  number  of  students 
should  make  observations  in  as  short  a  time  as  possible,  one  calorimeter 
can  be  allotted  to  each  subject,  the  other  hand  being  kept  in  the  pocket 
or  covered  with  a  glove  if  the  room  is  cool,  so  as  to  avoid  reflex  vaso- 
motor interference.  A  felt  collar  is  chosen  which  fits  the  wrist  closely. 
A  horizontal  pencil-mark  is  made  at  the  lower  edge  of  the  styloid 
process  of  the  ulna,  and  another  parallel  mark  at  a  distance  above  this 
slightly  greater  than  the  thickness  of  the  collar.  When  this  second 
mark  is  just  kept  in  view  above  the  collar  with  the  hand  in  the 
calorimeter,  the  first  (lower)  mark  will  be  just  below  the  level  of  the 
lid.  A  large  bath  holding  20  or  30  litres  or  more  (a  clean  '  garbage  ' 
or  '  offal '  can  is  suitable)  is  filled  with  water  at  about  32°  C.  The 
exact  temperature  is  not  important,  but  it  should  be  about  the  same 
in  all  measurements  which  are  to  be  compared.  An  ordinary  ther- 
mometer graduated  in  degrees  is  all  that  is  necessary  for  reading  the 
temperature  of  the  bath.  The  calorimeters  are  now  filled  from  the 
bath.  They  are  conveniently  made  of  such  a  size  that  3  litres  of  water 
and  the  hand  can  be  contained  in  them  without  any  slopping  over 
when  the  water  is  stirred.  Time  is  saved  by  having  a  metal  flask 
which  just  holds  the  quantity  of  water  that  goes  into  each  calorimeter. 
The  orifices  of  the  calorimeters  are  closed  by  felt  discs.  The  subject, 
sitting  in  a  high  chair  placed  between  the  calorimeters,  now  immerses 
his  hands  in  the  bath  to  a  point  between  the  two  marks.  The  fingers 
are  kept  spread.  The  bath  is  occasionally  stirred.  An  ordinary  ther- 
mometer suspended  at  the  back  of  the  chair  gives  the  room  tempera- 
ture. After  ten  minutes  the  hands  are  withdrawn  from  the  bath,  the 
wrists  rapidly  dried  with  a  towel,  the  hands  at  once  introduced  into  the 
calorimeters,  and  the  felt  collars  adjusted  round  the  wrists.  The  sub- 
ject leans  back  comfortably  in  the  chair,  allowing  the  arms  to  hang 
down  without  effort.  The  fingers  are  kept  slightly  spread.  The  ob- 
server sits  on  a  low  seat  behind  the  subject,  and  reads  the  thermometers 
from  time  to  time,  always  after  stirring  the  water  well  with  goose- 
feathers  passing  through  the  stirring-holes  in  the  lid.  The  readings 
can  be  made  at  intervals  of  a  minute,  two  minutes,  or  any  interval 
which  is  convenient.  At  the  end  the  hands  are  quickly  withdrawn, 
the  felt  discs  put  over  the  orifices,  and  the  water  vigorously  stirred  for 
ten  or  fifteen  seconds  before  the  thermometers  are  read.  In  this  way 
any  errors  due  to  imperfect  stirring  or  to  accidental  contact  of  the 
hands  with  the  thermometers  arc  eliminated. 

The  volume  of  each  hand  is  now  measured  by  immersing  it  exactly 
to  the  lower  mark  in  water  contained  in  a  glass  douche-can  connected 
by  a  short  rubber  tube  with  a  pipette  furnished  with  a  side-tube  at  its 
lower  end.  The  lowest  graduation  on  the  burette  (50  on  a  50  c.c. 
burette)  is  brought  level  with  the  water  before  the  hand  is  immersed. 
While  the  hand  is  being  held  steadily  and  vertically  in  the  water  by 
an  assistant,  the  level  of  the  water  in  the  burette  is  read  off.     All  that 


PRACTICAL  EXERCISES 


219 


is  necessary  to  get  the  volume  of  the  hand  is  to  pour  water  into  the 
can  from  a  graduated  measure  after  withdrawal  of  the  hand  until  the 
same  level  is  reached.  Or  the  value  of  a  division  of  the  burette  can 
be  determined  once  for  all.  The  burette  is  simply  used  as  a  transparent 
scale.  When  the  two  hands  are  successively  measured,  the  small 
amount  of  water  removed  by  the  first  is  automatically  restored  by 
dipping  the  second  into  a  separate  vessel  of  water,  and  putting  it  wet 
into  the  douche-can.  The  rectal  t  mpcrature  should  now  be  obtained. 
The  temperature  of  the  arterial  blood  entering  the  hand  is  taken  as 
0-5°  C.  below  that  of  the  rectum.  If  only  the  mouth  temperature  can 
be  got,  the  thermometer  should.be  put  in  a  second  time  without  shaking 


-Calorimetric 


uicasurin^   Blood-Flow  in  Hands. 


down  to  see  if  it  rises  any  more.  The  mouth  temperature  is  taken  as 
equal  to  the  arterial  blood  temperature. 

After  thorough  stirring,  the  calorimeter  temperatures  can  now  be 
read  again.  The  two  being  noted,  the  amount  of  cooling  of  the  calor- 
imeters can  be  determined.  This  has  to  be  added  to  the  actually 
observed  rise  of  the  thermometers  during  immersion  of  the  hands. 

Suppose  an  experiment  yielded  the  following  data:  Rise  of  ther- 
mometer in  a  calorimeter  in  twenty  minutes  during  immersion  of  a  hand 
in  it,  10°  C. ;  temperature  of  calorimeter  at  beginning  of  the  twenty 
minutes,  310°  C;  at  end  of  twenty  minutes,  320°  C:  cooling  of  calor- 
imeter in  twenty  minutes,  oi°  C. ;  water  in  calorimeter,  3,000  c.c; 


220  THE  CIRCULATION  OF  THE  BLOOD  AND  LYMPH 

volume  of  hand,  450  c.c;  rectal  temperature,  370°  C. ;  water  equivalent 
of  calorimeter,  100  c.c. 

The  water  equivalent  of  the  hand  is  450  x  08*=  360  c.c. 
The  water  equivalent  of  the  calorimeter  is  -  100  c.c. 
Water   ------     3,000  c.c. 


Total  -  -  -  -     3,460  c.c. 

3,460  X  I' I  =  3,806  small  calories  given  off  by  the  hand  in  twenty 
minutes. 

Temperature  of  arterial  blood  (36'5°)  minus  temperature  of  venous 
blood  (3i'5°,  the  mean  temperature  of  the  calorimeter)  =  5'o. 

Flow  per  minute  through  hand  =  ^^ x  —  '  =423  grm. 

Flow  per  100  c.c.  of  hand  per  minute  =  9*4  grm. 

The  readings  of  the  calorimeter  thermometers  for  the  first  one  or  two 
minutes  may  not  be  usable,  owing  to  disturbance  caused  by  the  intro- 
duction of  the  hands.  As  soon  as  they  begin  to  rise  steadily  and 
uniformly,  the  readings  can  be  utilized  for  the  calculation  of  the  flow. 

33.  Vasomotor  Reflexes. — Begin  as  in  32.  Then,  after  the  hands 
have  been  in  the  calorimeters  for  a  sufficient  period  (say  ten  minutes)  to 
allow  satisfactory  readings  for  the  determination  of  the  blood-flow  to 
be  obtained,  rapidly  transfer  one  hand  to  cold  water  (at  about  8°  C), 
while  the  other  remains  in  the  calorimeter.  Continue  reading  the 
calorimeter  thermometer.  Its  rise  will  be  checked  by  reflex  vaso- 
constriction. If  the  hand  is  kept  for  a  few  minutes  in  the  calorimeter, 
the  reflex  vaso-constriction  of  the  hand  in  the  calorimeter  wiU  probably 
disappear,  and  the  thermometer  will  rise  faster.  WTien  a  sufficient 
number  of  readings  have  been  obtained  for  calculating  the  alteration 
in  the  flow,  which  will  usually  be  the  case  in  eight  or  ten  minutes, 
transfer  the  hand  from  the  cold  water  to  warm  water  (at  about  43°  C), 
and  continue  reading  the  calorimeter  thermometer.  There  is  usually 
a  reflex  vaso-constrittion  followed  by  vaso-dilatation. 

*  This  factor  is  the  product  of  the  specific  gravity  and  the  specific  heat  of 
the  hand.  The  volume  multiplied  by  the  specific  gravity  gives  the  mass  of 
the  hand,  which  multiplied  by  the  specific  heat,  gives  the  water  equivalent  of 
the  hand. 

t  The  reciprocal  of  the  specific  heat  of  blood  (see  formula,  p.  122), 


CHAPTER  IV 

RESPIRATION 

Respiration  in  its  widest  sense  is  the  sum  total  of  the  processes  bj' 
which  the  ultimate  elements  of  the  body  gain  the  oxygen  they 
require,  and  get  rid  of  the  carbon  dioxide  they  produce. 

Section. I. — Preliminary  Anatomical  Data. 

Comparative. — In  a  unicellular  organism  no  special  mechanism  of 
respiration  is  needed;  the  oxygen  diffuses  in,  and  the  carbon  dioxide 
diffuses  out,  through  the  general  surface.  The  simple  wants  of  such 
multicellular  animals  as  the  coelenterates,  the  group  to  which  the  sea- 
anemone  belongs,  are  also  supplied  by  diffusion  through  the  ectoderm 
from  and  into  the  surrounding  water,  and  through  the  endoderm  from 
and  into  the  contents  of  the  body-cavity-  and  its  ramifications. 

But  in  animals  of  more  complex  structure  special  arrangements 
become  necessary,  and  respiration  is  di\'ided  into  two  stages:  (i)  Ex- 
ternal respiration,  an  interchange  between  the  air  or  water  and  a  cir- 
culating medium  or  blood  as  it  parses  through  richly  vascular  skin, 
gills,  tracheae,  or  lungs;  and  (2)  internal  respiration,  an  interchange 
between  the  blood,  or  lymph,  and  the  cells. 

In  the  lower  kinds  of  worms  respiration  goes  on  solely  through  the 
skin,  under  which  plexuses  of  bloodvessels  often  exist,  but  in  some 
higher  worms  there  are  special  vascular  appendages  that  play  the  part 
of  gills.  The  Crustacea  also  possess  gills,  while  in  the  other  arthropoda 
respiration  is  carried  on  either  by  the  general  surface  of  the  body  (in 
some  low  forms),  or  more  commonly  by  means  of  trachea;,  or  branched 
tubes  surrovmded  by  blood  spaces  and  commimicating  externally  with 
the  air  and  internally  by  their  finest  twigs  with  the  individual  cells. 
Most  of  the  mollusca  breathe  by  gills,  but  a  few  only  by  the  skin. 

Among  vertebrates  the  fishes  and  larved  amphibians  breathe  by  gills, 
but  most  adult  amphibians  have  lungs.  The  skin,  too,  in  such  animals 
as  the  frog  has  a  very  important  respiratory^  function,  more  of  the 
gaseous  exchange  taking  place  through  it  in  some  conditions  than 
through  the  lungs. 

One  small  group  of  fiishes,  the  dipnoi,  has  the  peculiarity  of  possessing 
both  gills  and  a  kind  of  lungs,  the  swim-bladder  being  surrounded  with 
a  plexus  of  bloodvessels  and  taking  on  a  respiratory  function. 

In  all  the  higher  vertebrates  the  respiration  is  carried  on  by  lungs; 
the  trifling  amount  of  gaseous  interchange  which  can  possibly  take 
place  through  the  skin  is  not  worth  taking  into  account.  The  lungs 
are  to  be  regarded  as  developed  from  outgro\\i:hs  of  the  alimentary* 
canal,  beginning  near  the  mouth. 

221 


222  RESPIRA  TION 

The  object  of  all  special  respiratory  arrangements  being,  in  the  first 
instance,  to  facilitate  the  gaseous  exchange  between  the  surrounding 
medium  (air  or  water)  and  the  blood,  a  prime  necessity  of  a  respiratory 
organ,  be  it  skin,  gill,  trachea,  or  lung,  is  a  free  supply  of  blood,  in 
vessels  so  fine  and  thin  that  diffusion  readily  takes  place  into  them 
and  out  of  them.  But  a  free  supply  of  blood  would  be  of  no  avail  if  the 
medium  to  which  the  blood  gave  up  its  carbon  dioxide  and  from  which 
it  drew  its  oxygen  was  not  being  constantly  and  sufficiently  renewed. 

Sometimes  the  natural  currents  of  the  water  or  the  air  are  of  them- 
selves suf&cient  to  secure  this  renewal ;  in  other  cases,  artificial  currents 
are  set  up  by  cilia,  or  special  bailing  organs,  like  the  soaphognathites 
of  the  lobster.  In  all  the  higher  animals,  active  movements  by  which 
air  or  water  is  brought  into  contact  with  the  respiratory  surfaces,  are 
necessary;  and  it  is  possible  that  such  movements  take  place  even  in 
the  tracheae  of  insects  and  other  air-breathing  arthropoda.  Fishes,  by 
rhythmical  swallowing  movements,  take  in  water  through  the  mouth 
and  pass  it  over  the  gills  and  out  by  the  gill-slits,  while  the  frog  distends 
its  lungs  by  swallowing  air. 

Physiological  Anatomy  of  the  Respiratory  Apparatus.— In  man  the 
respiratory  apparatus  consists  of  a  tube  (the  trachea)  widened  at  its 
upper  part  into  the  larynx,  which  contains  the  special  mechanism  of 
voice,  and  communicates  through  the  nose  or  mouth  with  the  external 
air.  Below,  the  trachea  divides  dendritically  into  innumerable 
branches,  the  ultimate  divisions  of  which  are  called  bronchioles.  Each 
bronchiole  breaks  up  into  several  wider  passages,  or  infundibula,  the 
walls  of  which  are  everywhere  pitted  with  recesses  or  alcoves,  called 
alveoli.  The  infundibula  constitute  the  essential  distensible  elements 
of  the  lung,  by  the  alternate  stretching  and  relaxation  of  which  the 
respiratory  changes  in  the  volume  of  the  organ  are  mainly  brought 
about.  The  trachea  and  larger  bronchi  are  strengthened  by  hyaline 
cartilage  in  the  form  of  incomplete  rings,  connected  behind  by  non- 
striped  muscular  fibres,  which  also  exist  in  the  intervals  between  the 
rings.  The  middle-sized  bronchi  within  the  lungs  have  the  cartilage 
in  the  form  of  detached  pieces  in  the  outer  portion  of  the  wall,  while 
nearer  the  lumen  lies  a  complete  ring  of  non-striped  muscle. 

In  the  bronchioles,  no  cartilage  is  present,  but  the  circularly-arranged 
muscular  fibres  still  persist,  and  also  form  a  thin  layer  in  the  infundi- 
bula. In  the  air-cells,  or  alveoli,  however,  there  are  no  muscular  fibres. 
Their  walls  consist  essentially  of  a  network  of  elastic  fibres,  continuous 
with  a  similar  layer  in  the  infundibula  and  bronchioles,  and  covered  on 
the  side  next  the  lumen  by  a  single  layer  of  large,  clear  epithelial  scales, 
with  here  and  there  a  few  smaller  and  more  granular  polyhedral  cells. 

From  the  larynx  to  the  bronchioles  the  mucous  membrane  is  ciliated 
on  its  free  surface,  the  cilia  lashing  upwards  so  as  to  move  the  secre- 
tion towards  the  larynx  and  mouth.  In  the  infundibula  the  ciliated 
epithelium  begins  to  disappear,  and  is  absent  from  the  alveoli.  Part 
of  the  nasal  cavity  and  the  upper  part  of  the  pharynx  are  also  lined  with 
ciliated  epithelium.  Mucous  glands  are  present  in  abundance  in  the  upper 
portions  of  the  respiratory  passages,  but  disappear  in  the  smaller  bronchi. 

Blood-Supply  of  the  Lungs. — The  quantity  of  blood  traversing  the 
lungs  bears  no  proportion  to  the  amount  required  for  their  actual 
nourishment.  Small,  however,  as  this  latter  quantity  is,  it  cannot 
apparently  be  derived  from  the  vitiated  blood  of  the  right  ventricle, 
but  is  obtained  directly  from  the  aortic  system  by  the  bronchial  arteries. 
These  are  distributed,  with  the  bronchi,  which  they  supply  as  well  as 
the  connective  tissue  of  the  interlobular  septa  running  through  the 


PRELIMINARY  ANATOMICAL  DATA  223 

substance  of  the  lung,  the  pleura  lining  it  and  the  walls  of  the  large 
bloodvessels.  Most  of  the  blood  from  the  bronchial  arteries  is  returned 
by  the  bronchial  veins  into  the  systemic  venous  system,  but  some  of  it 
finds  its  way  by  anastomoses  into  the  pulmonary  veins. 

The  branches  of  the  pulmonary  artery  are  also  distributed  with  the 
bronchi,  and  break  up  into  a  dense  capillary  network  around  the  alveoli. 
From  the  capillaries  veins  arise  which,  gradually  uniting,  form  the  large 
pulmonary  veins  tliat  pour  their  blood  into  the  left  auricle. 

The  same  quantity  of  blood  must,  on  the  whole,  pass  per  unit  of 
time  through  the  lesser  as  through  the  greater  circulation,  other\vise 
equilibrium  could  not  exist,  and  blood  would  accumulate  either  in  the 
lungs  or  in  the  systemic  vessels.  But  it  does  not  follow  that  at  each 
heart-beat  the  output  of  the  two  ventricles  is  exactly  equal.  If,  indeed, 
the  capacity  of  the  lesser  circulation  were  constant,  the  quantity 
driven  out  at  one  systole  by  the  right  ventricle  would  be  the  same  as 
that  ejected  at  the  next  by  the  left  ventricle.  But  it  is  known  that 
the  capacity  of  the  pulmonary  vessels  is  altered  by  the  movements 
of  respiration  and  probably  in  other  ways,  so  that  it  is  only  on  the 
average  of  a  number  of  beats  that  the  output  of  the  two  ventricles  can 
be  supposed  equal. 

The  time  required  by  a  given  small  portion  of  blood — e.g.,  by  a  single 
corpuscle — ^to  complete  the  round  of  the  lesser  circulation,  is,  as  we 
have  seen  (p.  137),  much  less  than  the  average  time  needed  to  complete 
the  systemic  circulation.  In  man  the  ratio  is  probably  about  i  :  5. 
Since  all  the  blood  in  a  vascular  tract  must  pass  out  of  it  in  a  period 
equal  to  the  circulation  time,  the  average  quantity  of  blood  in  the 
lungs  and  right  heart  of  a  man  would  thus  be  about  one-fifth  of  that  in 
the  systemic  vessels.  That  is  to  say,  not  less  than  700  grm.  out  of  the 
4^  kilos*  of  blood  in  a  70-kilo  man  would  be  contained  in  the  lesser  cir- 
culation, and  about  3|-  kilos  in  the  greater.  This  corresponds  sufficiently 
well  with  calculations  from  other  data. 

For  example,  the  average  weight  of  the  lungs  in  three  persons  exe- 
cuted by  beheading,  was  457  grm.  (Gluge).  The  average  weight  of 
the  lungs  in  a  great  number  of  persons  who  had  died  a  natural  death 
was  1,024  grm.  (Juncker).  The  weight  of  the  pulmonary  tissue  alone 
in  the  first  set  of  cases  must  be  less  than  457  grm.,  for  the  lungs  of  a 
person  who  has  bled  to  death  are  never  bloodless.  In  a  dog  killed  by 
bleeding  from  the  carotid,  one-quarter  of  the  weight  of  the  lungs  con- 
sisted of  blood.  Assuming  the  same  proportion  for  the  decapitated 
individuals,  we  get  343  grm.  as  the  net  weight  of  the  blood-free  lungs. 
Deducting  this  from  1,024  grm.,  we  arrive  at  681  grm.  as  the  average 
quantity  of  blood  in  the  lungs.  Adding  to  this  the  quantity  in  the 
right  side  of  the  heart  (p.  140),  we  get,  in  round  numbers,  750  grm. 
as  the  amount  in  the  lesser  circulation.  It  is  true  that  in  the  living 
body  the  conditions  arc  not  the  same  as  after  death ;  but  it  is  probable 
that  in  a  large  number  of  cases  taken  at  random  the  differences  would 
be  approximately  equalized. 

It  has  been  further  calculated  that  the  total  area  of  the  alveolar 
surface  of  the  lungs  of  a  man  is  about  100  square  metres  (sixty  times 
greater  than  the  area  of  the  skin),  of  which,  perhaps,  75  square  metres 
are  occupied  by  capillaries.  The  average  thickness  of  this  immense 
sheet  of  blood  has  been  reckoned  to  be  equal  to  the  diameter  of  a  red 
blood-corpuscle,  or,  say,  8  /i.  This  would  give  600  c.c.  (630  grm.)  as 
the  quantity  of  blood  in  the  lungs,  which  is  probably  somewhat  too 
low  an  estiniate. 

*  See  footnote  on  p.  139 


224  RESPIRA  TION 

If   we  take  the  pulmonary  circulation-time  as  13  seconds  (p.  137), 

and  the  quantity  of  blood  in  the  lungs  as  700  grm.,  then   -^ — 

=  194  kilos  of  blood  will  pass  through  the  lungs  in  an  hour,  or  4,65b 
kilos  (say,  4,400  litres)  in  twenty-four  hours.  This  would  fill  a  cubical 
tank  in  which  the  man  could  almost  stand  upright  with  the  lid  closed. 

Section  II. — Mechanical  Phenomena  of  External 
Respiration. 

The  lungs  are  enclosed  in  an  air-tight  box,  the  thorax;  or  it  may 
be  said  with  equal  truth  that  they  form  part  of  the  wall  of  the 
thoracic  cavity,  and  the  part  which  has  by  far  the  greatest  capacity 
of  adjustment.  The  alveolar  surface  of  the  lungs  is  in  contact  with 
the  air.  The  pleura,  which  covers  their  internal  surface,  is  reflected 
over  the  chest-walls  and  diaphragm,  so  as  to  form  two  lateral  sacs, 
the  pleural  cavities.  In  health  these  are  almost  obliterated,  and  the 
visceral  and  parietal  pleurae,  separated  and  lubricated  by  a  few 
drops  of  lymph,  glide  on  each  other  with  every  movement  of 
respiration.  But  in  disease  the  pleural  cavities  may  be  filled  and 
their  walls  widely  separated  by  exudation,  as  in  pleurisy,  or  by 
blood,  as  in  rupture  of  an  aneurism,  or  by  air  in  the  condition 
known  as  pneumo-thorax.  Between  the  two  pleural  sacs  lies  a  mesial 
space,  the  mediastinum,  commonly  divided  into  an  anterior  medias- 
tinum in  front  of  the  heart,  and  a  posterior  mediastinum  behind  it. 
The  pleural  and  pericardial  sacs  and  the  mediastinum  constitute 
together  the  thoracic  cavity.  The  external  surface  of  the  chest- 
wall  and  the  alveolar  surface  of  the  lungs  are  subjected  to  the 
pressure  of  the  atmosphere,  to  which  the  pressure  in  the  thoracic 
cavity  (intra-thoracic  pressure)  would  be  exactly  equal  if  its  bound- 
aries were  perfectly  yielding.  But  in  reality  the  intra-thoracic 
pressure  is  always  normally  something  less  than  this.  For  even 
the  lungs,  the  least  rigid  part  of  the  boundary,  oppose  a  certain 
resistance  to  distension,  and  so  hold  off,  as  it  were,  from  the  thoracic 
cavity  a  portion  of  the  alveolar  pressure;  and  in  any  given  position 
of  the  chest  the  intra-thoracic  pressure  is  equal  to  the  atmospheric 
pressure  minus  this  elastic  tension  of  the  lungs. 

The  object  of  the  respiratory  movements  is  the  renewal  of  the  air 
in  contact  with  the  alveolar  membrane — in  other  words,  the  ventila- 
tion of  the  lungs.  Two  main  methods  are  followed  by  sanitary 
engineers  in  the  ventilation  of  buildings:  they  force  air  in,  or  they 
draw  it  in.  In  both  cases  the  movement  of  the  air  depends  on  the 
estabhshment  of  a  slope  of  pressure  from  the  inlet  to  the  interior. 
In  the  first  method,  this  is  done  by  increasing  the  pressure  at  the 
inlet;  in  the  second,  by  diminishing  the  pressure  at  the  outlet.  In 
certain  animals  Nature,  in  solving  its  problem  of  ventilation,  has 
made  use  of  the  first  i)rinciple.     Thus,  the  frog  forces  air  into  its 


MECHANICAL  PHENOMENA   OF  EXTERNAL  RESPIRATION      225 


lungs  by  a  swallowing  movement.  In  artificial  respiration,  as 
practised  in  physiological  experiments,  the  same  method  is  usually 
employed:  air  is  driven  into  the  lungs  under  pressure.  But  in  the 
vast  majority  of  air-breathing  animals,  including  man,  the  opposite 
principle  has  been  adopted;  and  the  '  indraught  '  of  air  from  nose 
and  pharynx  to  alveoli  is  not  set  up  by  increasing  the  pressure  in 
the  former,  but  by  diminishing  it  in  the  latter.  This  '  indraught,' 
or  inspiration,  is  brought  about  by  certain  movements  of  the  chest- 
wall,  which  increase  the  capacity  of  the 
thoracic  cage  and  lower  the  pressure  in  the 
thoracic  cavity.  The  expansion  of  the 
highly-distensible  lungs  keeps  pace  with 
the  diminution  of  pressure  in  the  pleural 
sacs,  and  they  follow  at  every  point  the 
retreating  chest  -  wall  and  diaphragm, 
although  they  do  not  expand  equally  in 
all  directions.  The  dorsal  surface  in  con- 
tact with  the  vertebral  column,  the 
mediastinal  surface  in  contact  with  the 
pericardium  and  the  contents  of  the 
mediastinum,  and  the  surface  of  the  apex, 
move  but  little.  The  surfaces  in  contact 
with  the  diaphragm,  ribs,  and  sternum 
have  the  greatest  range  of  movement. 
Intermediate  portions  of  the  parenchyma 
of  the  lungs  expand  in  a  degree  determined 
by  their  distance  from  the  relatively 
stationary  and  mobile  surfaces.  The  pres- 
sure of  the  air  in  the  alveoli  during  the 
rapid  expansion  of  the  lungs  necessarily 
sinks  below  that  of  the  atmosphere,  and 
air  rushes  in  through  the  trachea  and 
bronchi  till  the  difference  is  equalized. 
Then  commences  the  movement  of  ex- 
piration. The  expanded  chest  falls  back 
to  its  original  limits;  the  pressure  in  the 
thoracic  cavity  increases;  the  distended 
lungs,  in  virtue  of  their  elasticity,  shrink  to  their  former  volume; 
the  pressure  of  the  air  in  the  alveoli  rises  above  that  of  the  atmo- 
sphere, and  with  this  reversal  of  the  slope  of  pressure  air  streams 
out  of  the  bronchi  and  trachea. 

In  inspiration  the  chest  dilates  in  all  its  diameters.  Its  vertical 
diameter  is  increased  by  the  contraction  of  the  diaphragm,  which, 
composed  of  a  central  tendon,  a  peripheral  ring  of  muscular  tissue, 
and  the  two  muscular  crura,  bulges  up  into  the  thorax  in  the  form 
of  two  flattened  domes,  one  on  each  side,  and  thus  closes  its  lower 

15 


Fig.  109.  —  Scheme  to  illus- 
trate the  ^lovements  of  the 
Lungs  in  the  Chest.  T  is 
a  bottle  from  which  the 
bottom  has  been  removed; 
D,  a  flexible  and  elastic 
membrane  tied  on  the 
bottle,  and  capable  of  being 
pulled  out  by  the  string  S 
so  as  to  increase  the  ca- 
pacity of  the  bottle.  L  is 
a  thin  elastic  bag  repre- 
senting the  lungs.  It  com- 
municates with  the  external 
air  by  a  glass  tube  fitted 
airtight  through  a  cork  in 
the  neck  of  the  bottle. 
When  D  is  drawn  down,  the 
pressure  of  the  external  air 
causes  L  to  expand.  When 
the  string  is  let  go.  L  con- 
tracts again,  in  virtue  of 
its  elasticity. 


226  RESPIRATION 

aperture.  When  the  diapliragm  contracts,  even  in  ordinary  quiet 
breathing,  the  central  tendon  descends  distinctly  (about  half  an 
inch)  after  the  manner  of  a  piston.  The  acute  angle  which  the 
muscular  ring  makes  during  relaxation  with  the  thoracic  wall  opens 
out  around  its  whole  circumference,  so  as  to  form  a  groove  of  trian- 
gular section.  But  the  most  peripheral  portion  of  the  ring  is  always 
kept  in  close  apposition  to  the  chest- wall  by  the  negative  intra- 
thoracic pressure.  The  lungs  follow  the  descending  diaphragm, 
their  lower  borders  keeping  accurately  in  contact  with  it.  The 
descent  of  the  diaphragm  is  not  directly  downwards,  but  downwards 
and  forwards.  For  it  is  compounded  of  two  movements,  the  spinal 
segment  of  the  muscle  (the  crura)  causing  a  vertical  elongation  of 
the  thorax,  while  the  sterno-costal  part  (the  muscular  ring)  pushes 
the  abdominal  viscera  downwards  and  forwards  (Keith).  Since 
the  diaphragm  is  attached  to  the  lower  ribs,  there  is  a  tendency 
during  its  contraction  for  these  to  be  drawn  inwards  and  upwards; 
but  this  is  opposed  by  the  pressure  of  the  abdominal  viscera,  and  by 
the  action  of  the  quadratus  lumbonim,  which  fixes  the  twelfth  rib, 
and  of  the  serratus  posticus  inferior,  which  draws  the  lower  four 
ribs  backward.  When  these  and  the  other  inspiratory  muscles 
that  act  especially  upon  the  ribs  are  paralyzed  by  injury  to  the 
spinal  cord,  and  respiration  is  carried  on  by  the  diaphragm  alone, 
the  line  of  its  attachment  to  the  ribs  is  distinctly  marked  during 
inspiration  by  a  shallow  circular  groove. 

The  thorax  is  also  enlarged  by  the  action  of  certain  muscles  that 
act  upon  the  ribs.  Among  the  elevators  of  the  ribs,  as  their  name 
indicates,  are  usually  reckoned,  although  erroneously,  the  levatores 
costarum — ^twelve  in  number  on  each  side.  They  arise  from  the 
transverse  processes  of  the  last  cervical  and  first  eleven  dorsal 
vertebrae,  and  passing  obliquely  downwards  and  outwards,  are  in- 
serted between  the  tubercle  and  the  angle  into  the  first  or  second  rib 
below  their  origin.  They  do  not  elevate  the  ribs,  but  take  part  in 
lateral  movements  of  the  spinal  column.  The  scalene  muscles, 
which  may  in  a  lean  person  be  felt  to  be  tense  during  inspiration, 
fix  the  first  and  second  ribs  (scalenus  anticus  and  medius,  the  first ; 
scalenus  posticus,  the  second  rib),  and  so  afford  a  fixed  line  for  the 
intercostal  muscles  to  work  from  on  the  lower  ribs. 

The  most  important  elevators  of  the  ribs  are  the  external  inter- 
costals.  The  intercartilaginous  portions  of  the  internal  inter- 
costals  (the  intdrcartilaginei  muscles,  as  they  are  sometimes  called) 
also  contract  simultaneously  with  the  diaphragm,  and  may  there- 
fore be  included  in  the  list  of  inspiratory  muscles;  but  instead  of 
elevating  the  ribs  they  depress  the  costal  cartilages,  and  thus  help 
to  widen  the  angles  between  them  and  the  ribs.  In  addition  to 
increasing  the  capacity  of  the  chest,  the  contraction  of  the  external 
intercostals  and  the  intercartilaginous  muscles  aids  in  inspiration 


MECHANICAL  PHENOMENA   OF  EXTERNAL  RESPIRATION      227 

by  augmenting  the  rigidity  of  the  intercostal  spaces,  and  so  pre- 
venting tliem  from  being  drawn  in  as  easily  as  would  otherwise  be 
the  case  when  the  thorax  is  expanded  by  the  action  of  the  dia- 
phragm and  the  other  inspiratory  muscles. 

Lea\ang  out  of  account  the  floating  ribs,  which  functionally  form 
a  part  of  the  abdominal  wall,  the  ribs  in  relation  to  their  respiratory 
functions  may  be  divided  into  the  following  groups:  (i)  The  first 
rib,  which,  moving  itself  very  httle,  provides  a  fixed  line  towards 
which  the  next  set  of  ribs  may  be  raised. 

(2)  An  upper  costal  series  consisting  of  the  ribs  from  the  second 
to  the  fifth.  These  are  raised  in  inspiration  towards  the  fixed  first 
rib  by  the  contraction  of  the  intercostal  muscles.  The  movement 
of  these  ribs  is,  mainly  at  any  rate,  a  rotation  around  a  transverse 
axis,  the  axes  on  which  they  move  corresponding  to  their  necks. 
The  manner  in  which  they  are  articulated  to  the  vertebrae  prevents 
any  sensible  rotation  around  an  antero-posterior  axis  or  '  bucket- 
handle  '  movement.  Since  these  ribs  slant  downwards  and  forwards 
to  their  sternal  attachments,  the  sternum  is  raised  when  they  are 
elevated;  or,  rather,  since  the  manubrium  is  practically  immovable 
in  ordinary  breathing,  the  body  of  that  bone  is  bent  on  the  manu- 
brium at  the  manubrio-sternal  joint.  This  causes  an  increase  in 
the  antero-posterior  diameter  of  the  thorax.  Further,  since  the 
arches  formed  by  the  ribs  \^^den  in  regular  progression  from  above 
downwards  in  the  upper  portion  of  the  thoracic  cage,  so  that  the 
second  rib  is  a  segment  of  a  larger  circle  than  the  first,  and  the 
third  than  the  second,  it  is  clear  that  a  general  elevation  of  the  chest 
will  tend  to  increase  the  transverse  diameter  at  any  given  level. 
Such  an  increase  is  also  favoured  by  the  opening  out  of  the  angles 
between  the  bony  ribs  and  the  costal  cartilages  under  the  influence 
of  the  couple  (or  pair  of  oppositely  directed  forces)  that  acts  on  them 
— viz.,  the  upward  pull  of  the  external  intercostals  exerted  on  the 
ribs,  and  the  downward  pull  of  the  intercartilaginei  and  the  resist- 
ance of  the  sternum  to  further  displacement  exerted  on  the  carti- 
lages. The  whole  arrangement  is  perfectly  adapted  to  permit  the 
expansion  of  the  roughly  conical  upper  lobes  of  the  lungs. 

(3)  The  lower  costal  series,  consisting  of  the  ribs  from  the  sixth 
to  the  tenth.  These  ribs,  with  their  muscles,  form  a  mechanism 
which  normally  acts  along  with  the  diaphragm  (Keith).  They  are 
so  arranged  that  in  inspiration  the  lateral  and  anterior  part  of 
each  moves  outwards  to  a  greater  extent  than  the  one  above  it. 
There  is  not  only  a  rotation  around  a  transverse  axis,  by  which  the 
lower  end  of  the  sternum,  connected  to  these  ribs  by  the  combined 
cartilages  of  the  sixth  to  the  ninth,  is  elevated,  but  also  a  rotation 
around  an  antero-posterior  axis.  The  movement  of  the  lower  ribs 
results,  therefore,  in  increasing  both  the  back-to-front  diameter  and 
the  transverse  diameter  of  the  lower  portion  of  the  thorax.     The 


228  RESPIRA  TION 

widening  of  the  thorax  from  side  to  side  may  also  be  in  a  slight 
degree  ascribed  to  a  twisting  movement  of  the  ribs,  which  tends  to 
evert  their  lower  borders.  With  the  diaphragm,  these  lower  ribs 
arranged  in  a  vertical  series  of  not  very  different  curvature  con- 
stitute a  mechanism  for  the  inspiratory  expansion  of  the  roughly 
cyHndrical  lower  lobes  of  the  lungs. 

Expiration  in  perfectly  tranquil  breathing  is  brought  about  with 
less  aid  from  active  muscular  contraction.  The  sense  of  effort 
disappears  as  soon  as  the  chest  ceases  to  expand.  The  diaphragm 
and  the  elevators  of  the  ribs  relax.  The  structures  that  have  been 
stretched  or  twisted  recoil  into  their  original  positions;  the  struc- 
tures that  have  been  raised  against  the  force  of  gravity  fall  back 
by  their  weight,  and  in  the  measure  in  which  the  pressure  increases 
in  the  thoracic  cavity  the  elasticity  of  the  lungs  causes  them  to 
shrink.  The  pressure  in  the  alveoh,  which  at  the  end  of  inspiration 
was  just  equal  to  that  of  the  atmosphere,  is  thus  increased,  and  the 
air  expelled.  It  is  probable  that,  even  in  man  and  in  quiet  respira- 
tion, the  interosseous  portions  of  the  internal  intercostals  help  by 
their  contraction  in  depressing  the  ribs,  and  that  a  slight  contrac- 
tion of  the  abdominal  muscles  hastens  the  return  of  the  diaphragm 
to  its  position  of  rest.  In  reptiles  and  birds,  expiration  is  normally 
effected  by  an  active  muscular  contraction.  This  is  also  true  in 
some  mammals — the  rabbit,  for  instance,  in  which  the  external 
oblique  muscles  of  the  abdominal  wall  take  an  important  share  in 
the  expiratory  act. 

T3rpes  of  Respiration. — Differences  exist  also,  not  only  between 
different  groups  of  animals,  but  even  between  women  and  men,  in 
the  relative  importance  in  inspiration  of  the  diaphragm  and  the 
muscles  that  raise  the  lower  ribs  on  the  one  hand,  and  the  muscles 
that  elevate  the  upper  ribs  on  the  other.  When  the  movements  of 
the  diaphragm  predominate,  the  respiration  is  said  to  be  of  the 
abdominal  or  diaphragmatic  type  ;  when  the  movements  of  the  upper 
ribs  and  sternum  are  most  conspicuous,  of  the  costal  or  thoracic  type. 
In  abdominal  respiration,  the  inspiratory  movement  commences  at 
the  diaphragm,  and  then  involves  the  lower  ribs  and  the  tip  of  the 
sternum.  In  costal  respiration,  the  upper  ribs  initiate  the  move- 
ment, and  are  followed  by  the  abdomen.  In  the  rabbit,  during 
quiet  breathing,  the  respiration  is  purely  diaphragmatic,  the  ribs 
remain  motionless;  and  herbivorous  animals  in  general  conform 
more  or  less  closely  to  this  type.  In  the  carnivora,  on  the  contrary, 
the  costal  type  prevails.  Man  allies  himself  as  regards  his  respira- 
tion with  the  rabbit  and  the  sheep ;  he  uses  his  diaphragm  more  than 
his  upper  ribs.  Civihzed  woman  falls  into  the  class  of  the  wolf  and 
the  tiger;  she  uses  her  upper  ribs  more  than  her  diaphragm.  The 
cause  of  the  difference  between  men  and  women  has  been  much 
discussed.     It  is  not  a  primitive  sexual  difference,  for  it  is  far  from 


MECHANICAL   PHENOMENA    OF  EXTERNAL  RESPIRATION     229 

being  universal;  in  the  uncivilized  and  semi-civilized  races  that 
have  been  investigated,  the  women  breathe  like  the  men.  It  is 
therefore  probable  that  the  predominance  of  the  costal  type  among 
women  of  European  race  is  a  pecuUarity  developed  by  a  mode  of 
dressing  which  hampers  the  movements  of  the  diaphragm  while 
permitting  the  elevation  of  the  ribs.  This  conclusion  is  strengthened 
by  the  fact  that  in  children  no  difference  exists;  both  boys  and  girls 
show  the  abdominal  t3'pe  of  respiration. 

All  this  refers  to  ordinary  breathing.  In  forced  respiration,  when 
the  need  for  air  becomes  urgent,  costal  breathing  always  becomes 
prominent  ahke  in  men,  in  women,  and  in  animals,  for  by  elevation 
of  the  ribs  the  capacity  of  the  chest  can  be  increased  to  a  greater 
degree  than  by  any  contraction  of  the  diaphragm. 

In  forced  inspiration,  indeed,  all  the  muscles  that  can  elevate  the 
ribs  may  be  thrown  into  contraction,  as  well  as  other  muscles  which 
give  these  fixed  points  to  act  from.  During  a  paroxysm  of  asthma, 
for  example,  the  patient  may  grasp  the  back  of  a  chair  with  his 
hands,  so  as  to  fix  the  arms  and  shoulders  and  allow  the  pectorals 
and  serratus  magnus  to  raise  the  ribs.  Similarly  in  forced  expiration 
all  the  muscles  are  used  which  can  depress  the  ribs,  or  increase  the 
intra-abdominal  pressure  and  push  up  the  diaphragm. 

Artificial  Respiration. — An  efficient  pulmonary  ventilation  can  be 
obtained  by  various  methods  when  the  natural  breathing  is  in  abey- 
ance. In  animals  the  method  most  commonly  employed  for  ex- 
perimental purposes  is  the  rhythmical  inflation  of  the  lungs  by  a 
pump  or  bellows,  or  by  a  stream  of  compressed  air  which  is  regularly 
interrupted,  the  chest  being  allowed  to  collapse  after  each  inflation. 
When  the  animal  is  to  be  kept  alive  after  the  experiment  the  inflation 
is  produced  through  a  tube  introduced  through  the  glottis.  If  the 
animal  is  not  to  be  kept  alive,  the  apparatus  is  generally  connected 
with  a  cannula  in  the  trachea.  In  man  the  exchange  of  air  between 
the  atmosphere  and  the  lungs  may  be  most  readily  accomplished 
by  strong  rhythmical  compression  of  the  lower  part  of  the  chest. 
This  forces  out  some  of  the  air  from  the  lungs;  on  relaxing  the 
pressure  the  chest  expands  again  and  air  is  drawn  in.  Schafer  has 
shown  that  this  is  the  most  efficient  method  of  respiration  in  re- 
suscitation of  the  apparently  drowned.  '  The  patient  is  placed  face 
downwards  on  the  ground,  with  a  folded  coat  under  the  lower  part 
of  the  chest.  The  operator  puts  himself  athwart  or  at  tiie  side  of 
the  patient,  facing  his  head  and  kneeling  upon  one  or  both  knees 
(Fig.  110),  and  places  his  hands  on  each  side  over  the  lower  part 
of  the  back  (lowest  ribs).  He  then  slowly  throws  the  weight  of  his 
body  forward  to  bear  upon  his  own  arms,  and  thus  presses  upon 
the  thorax  and  forces  air  out  of  the  lungs.  He  then  gradually 
relaxes  the  pressure  by  bringing  his  own  body  up  again  to  a 
more  erect  position,  but  without  moving  the  hands.'     Air  is  thus 


230 


RESPIRA  TION 


drawn  into  the  lungs.     The  process  is  repeated  twelve  to  fifteen 
times  a  minute. 

Certain  accessory  phenomena  (movements  and  sounds)  are  asso- 
ciated with  the  proper  movements  of  respiration.  The  larynx  rises 
in  expiration,  and  sinks  in  inspiration.  The  glottis  (and  particu- 
larly its  posterior  portion,  the  glottis  respiratoria)  is  widened  during 
deep  inspiration  and  narrowed  during  deep  expiration.  The  same 
is  the  case  with  the  nostrils,  and,  indeed,  in  some  persons  the  alae 
nasi  move  even  in  ordinary  breathing.  It  has  long  been  known 
that  in  deep  respiration  changes  in  the  calibre  of  the  bronchi  syn- 
chronous with  the  respiratory  movements  may  occur.  In  young 
persons  it  may  be  directly  observed  with  the  bronchoscope,  an 
instrument  used  by  laryngologists  for  exploring  the  larger  bronchi, 

that  these  dilate 
in  inspiration 
and  constrict  in 
expiration  (In- 
galls).  In  part 
at  least  these 
movements  are 
passively  pro- 
duced by  the 
changes  of  intra- 
thoracic  pres- 
sure, but  it  has 
not  been  defi- 
nitely deter- 
mined whether 
they  are  not  in 
part  caused  by 
alternate  contraction  and  relaxation  of  the  circular  bronchial 
muscles.  To  these  muscles  has  sometimes  been  attributed  the 
function  of  regulating  the  flow  of  air  into  and  out  of  the  infundib- 
ula,  as  the  muscle  of  the  arterioles  regulates  the  distribution  of  the 
blood  in  the  organs. 

As  regards  the  respiratory  sounds,  all  that  is  necessary  to  be  said 
here  is  that  when  we  listen  over  the  greater  portion  of  the  lungs  with 
the  ear,  or,  much  better,  with  a  stethoscope,  a  soft  breezy  murmur, 
that  has  been  compared  to  1:he  rustUng  of  the  wind  througli  distant 
trees,  is  heard.  This  has  been  called  the  vesicular  murmur.  It  is  only 
heard  in  health  during  inspiration  and  the  very  beginning  of  expira- 
tion, and  is  louder  in  children  than  in  adults.  Around  the  larger 
bronchi  and  the  trachea  a  blowing  .sound  is  heard,  which  certainly 
originates  at  the  glottis,  and  is  strengthened  by  the  resonance  of  the 
air-tubes.  In  health  this  is  not  recognized  over  the  greater  portion  of 
the  lung.  But  in  certain  diseases  in  which  the  alveoli  arc  devoid  of 
air,  whether  from  compression  or  because  they  are  filled  up  with 
exudation,  and  in  other  conditions,  this  bronchial  or  tubular  breathing 


-Arliiicial  Respiration  in  Cases  of  Drowning  (after 
Schafer). 


MECHANICAL  PHENOMENA  OF  EXTERNAL  RESPIRATION      231 

may  be  heard  over  the  affected  area.  The  bronchi  themselves,  how- 
ever, must  still  be  patent  and  contain  air.  The  most  commonly 
accepted  explanation  is  that  the  laryngeal  soimd  is  better  conducted 
through  the  smaller  bronchi  towards  the  surface  of  the  lungs  when 
their  walls  have  been  rendered  more  rigid  by  the  solidification  of  the 
parenchyma,  in  spite  of  the  fact  that  the  consolidated  tissue  as  such 
does  not  conduct  the  sound  so  well  as  the  air-containing  alveoli.  It 
seems  probable  that,  in  addition,  the  columns  of  air  in  the  bronchi, 
which  are  encased  in  solid  tissue,  may  actually  increase  the  intensity 
of  the  transmitted  larjmgeal  murmur  by  resonance. 

It  has  been  much  debated  whether  the  vesicular  murmur  also  arises 
at  the  glottis,  and  is  modified  by  transmission  through  the  pulmonary 
tissue,  or  whether  it  arises  somewhere  in  the  terminal  bronchi,  the 
infundibula  or  the  alveoli.  Both  views  may  be  supported  by  certain 
arguments,  and  to  both  some  objections  may  be  raised.  The  fact 
appears  to  be  that  there  are  two  elements  in  the  inspiratory  murmur — 
a  true  vesicular  sound,  produced  about  the  place  where  the  terminal 
bronchioles  give  off  the  infundibula,  and  a  resonance  sound  set  up  in 
the  trachea  and  bronchi  by  the  glottic  murmur.  This  resonance  sound 
as  heard  over  portions  of  the  lung  containing  only  small  bronchi  has 
a  different  character  from  that  heard  over  large  bronchi,  inasmuch  as 
the  fundamental  note,  and  to  a  still  greater  extent  the  overtones 
(p.  304),  are  much  weakened  in  those  small  and  easily-distensible 
tubes.  The  true  vesicular  element  is  heard  all  over  the  lungs,  but 
the  resonant  laryngeal  element  in  large  animals,  like  the  horse  and  ox, 
dies  out  as  an  audible  murmur  before  it  reaches  the  remotest  lobules, 
and  can  only  be  distinguished  over  a  portion  of  the  pulmonary  area. 
When  the  glottic  sound  is  eliminated  by  causing  an  animal  to  breathe 
through  a  tracheal  fistula,  the  vesicular  murmur  is  still  heard,  and  in 
the  horse  is  even  somewhat  sharper  than  normal,  although  in  the  dog 
it  is  softer  and  weaker.  The  expiratory  murmur  does  not  seem  to 
contain  a  true  vesicular  element,  but  is  exclusively  due  to  the  resonance 
of  the  expiratory  glottic  soimd  (Marek).  It  is  generally  admitted,  and 
this  is  of  great  importance  in  practical  medicine,  that  when  the  normal 
vesicular  sound  is  heard  over  any  portion  of  the  lung  tissue,  it  may  be 
inferred  that  this  portion  is  being  properly  distended,  and  that  air  is 
freely  entering  its  alveoli. 

Up  to  this  point  we  have  contented  ourselves  with  a  purely 
qualitative  description  of  the  mechanical  phenomena  of  respiration. 
We  have  now  to  consider  their  quantitative  relations,  and  the 
methods  by  which  these  have  been  studied. 

The  expansion  of  the  lungs  in  inspiration  may  be  easily  demonstrated^ 
in  man,  and  even  a  rough  estimate  of  its  amount  obtained,  by  the  clinical' 
method  of  perffussion.  For  example,  the  resonant  note  that  is  elicited 
when  a  finger  laid  on  the  chest  at  a  part  where  it  overlies  the  right 
lung  is  smartly  struck  can  be  followed  down  until  it  is  lost  in  the  '  liver 
dulncss.'  If  the  lower  limit  of  the  resonant  area  be  marked  on  the 
chest-wall  first  in  full  inspiration,  and  then  in  full  expiration,  the  mark 
will  be  lower  in  the  former  than  in  the  latter,  and  the  diUcrcnce  will 
represent  the  difference  in  the  vertical  length  of  the  shrunken  and  dis- 
tended lung.  A  similar  enlargement  in  the  transverse  direction  rriay 
be  demonstrated  in  the  same  way,  the  inner  borders  of  the  lungs  coming 
nearer  to  the  middle  line  in  inspiration,  and  receding  from  it  in  expira- 
tion.    The  examination  of  the  chest  by  the  Rontgen  rays  has  also 


232 


RES  PI  R  A  TION 


yielded  results  of  importance  in  the  study  of  normal  respiratory  con- 
ditions, and  still  more  important  results  in  pulmonary  disease. 

For  most  physiological  purposes,  however,  a  faithful  graphic  record 
of  the  respiratory  movements  is  indispensable.     This  may  be  obtained — 

(i)  By  registering  the  movements 
of  a  single  point,  or  the  variations  in 
a  single  circumference,  of  the  bound- 
ary of  the  thoracic  cavity.  In  man 
changes  in  the  circumference  of  the 
thorax  at  any  level  can  be  recorded 
by  means  of  a  tambour  adjusted  to 
the  chest  (Figs,  iii  and  134),  and  in 
communication  with  another,  which 
is  provided  with  a  writing  lever 
(Figs.  99  and  137).  Or  an  elastic 
tube,  with  a  spiral  spring  in  its 
lumen,  may  be  fastened  around  the 
tliorax  or  abdomen  and  connected 
with  a  piston-recorder  (a  small  cylin- 
der in  which  works  a  piston  carrying 
a  writing-point)  (Fitz). 

(2)  By  recording  the  changes  of 
pressure  produced  in  the  air-passages 
by  the  respiratory  movements.  This 
can  be  done  by  connecting  a  cannula 
in  the  trachea  of  an  animal  with  a 
recording  tambour  in  the  manner 
described  in  the  Practical  Exercises 
(p.  295).  The  variations  of  pressure 
may  be  measured  by  connecting  a 
manometer  with  the  trachea,  or  in 
man  with  the  nostril. 

(3)  By  writing  off  the  changes  of  pressure  which  occur  in  the  thoracic 
cavity  during  respiration.  For  this  purpose  a  trocar  (Fig.  113)  is  intro- 
duced through  an  intercostal  space  into  one  of  the  pleural  sacs,  without 
the  admission  of  air,  or  into  the  pericardium,  and  then  connected  with 
a  manometer  or  other  recording  apparatus.  Or  a  tube,  similar  in  con- 
struction to  a  car- 
diac sound  (p.  96), 
may  be  pushed 
down  the  oesopha- 
gus. The  varia- 
tions in  the  intra- 
thoracic pressure 
are  transmitted  to 
the  air  in  the  elas- 
tic bag,  and  thence 
to  a  tambour. 

(4)  In  the  rabbit 
the  part  of  the  dia- 
phragm attached  to  the  ensiform  cartilage  may  be  isolated  from  the 
rest  and  its  contractions  recorded  by  a  lever  (Head).  For  some  purposes 
this  is  the  best  method. 


Fig.  III. — Scheme  of  Tambour  for 
recording  Respiratory  Movements. 
C,  a  metal  capsule  connected  airtight 
with  B,  A,  two  caoutchouc  mem- 
branes, the  chamber  formed  by  which 
can  be  inflated  by  means  of  the  tube 
and  stopcock  E.  The  tube  D  con- 
nects the  space  H  with  a  registering 
tambour  provided  with  a  lever.  The 
membrane  A  is  applied  to  the  chest, 
round  which  the  inextensible  strings 
Fare  tied.  At  every  expansion  of  the 
chest  the  pressure  in  H  is  increased, 
and  the  increase  of  pressure  is  trans- 
mitted to  the  registering  tambour. 


Fig.   112. — Respiratory  Tracing  from  Man  (Marey). 
stroke,  inspiration;  up  stroke,  expiration. 


Down 


When  the  respiratory  movements  are  studied  in  any  of  these  ways, 
it  is  found  that  there  is  practically  no  pause  between  the  end  of 


MECHANICAL  PHENOMENA   OF  EXTERNAL  RESPIRATION     233 


d 


Fig.     113- 


Simple 


inspiration  and  the  beginning  of  expiration.  Nor,  although  the 
chest  collapses  more  gradually  than  it  expands,  is  there  any  distinct 
interval  in  ordinary  breathing  between  the  end  of  expiration  and 
the  beginning  of  the  succeeding  inspiration.  When,  however,  the 
respiration  is  unusually  slow,  an  actual  pause  (expiratory  pause) 
may  occur  at  this  point.  Expiration  takes 
somewhat  longer  time  than  inspiration,  the 
ratio  varying  from  7  :  6  to  3  :  2,  according  to 
age,  sex,  and  other  circumstances. 

The  frequency  of  respiration  is  by  no  means 
constant  even  in  health.  All  kinds  of  in- 
fluences affect  it.  It  is  difficult  even  to  direct 
the  attention  to  the  respiratory  act  without 
bringing  about  a  modification  in  its  rhythm. 
In  the  adult  15  to  20  respirations  per  minute 
may  be  taken  as  about  the  normal.  In  young 
children  the  frequency  may  be  twice  as  great 
(new-born  child,  50  to  70;  child  from  i  to  5 
years  old,  20  to  30  per  minute).  It  is  greater 
in  a  female  than  in  a  male  of  the  same  age.  A 
rise  of  temperature  increases  it;  150  respira- 
tions per  minute  have  been  seen  in  a  dog  with 
a  high  temperature.  Sudden  cooling  of  the  skin, 
exercise,  and  various  emotional  states,  increase 
the  rate,  and  sleep  diminishes  it.  The  will  can 
alter  the  frequency  and  depth  of  respiration 
for  a  time,  and  even  stop  it  altogether,  but  in 
less  than  a  minute,  in  ordinary  individuals,  the 
desire  to  breathe  becomes  imperative.  Cato's 
assertion  that  he  could  kill  himself  at  anytime 
'  merely  by  holding  his  breath  '  is  only  a  proof 
that  he  was  a  better  philosopher  than  physi- 
ologist. After  a  period  of  forced  respiration 
the  breath  can  be  held  for  a  much  longer  time. 
This  is  due  to  the  '  washing  out  '  of  the  carbon 
dioxide,  the  normal  stimulus  to  the  respiratory 
centre  (p.  276).  After  six  minutes  of  forced 
breathing  the  interval  of  voluntary  inhibition  can  be  extended  be- 
yond four  minutes.  A  professional  diver  has  remained  under  water 
in  a  tank  for  about  four  and  three-quarter  minutes.  When  oxygen 
is  inhaled  instead  of  air  during  the  last  few  breaths  of  the  forced 
respiration,  the  interval  during  which  the  breath  can  be  held  may 
be  much  increased  (up  to  nine  or  ten  minutes).  In  animals  the  rate 
of  respiration  can  be  greatly  affected  by  drugs  and  by  the  section 
and  stimulation  of  certain  nerves;  but  to  this  we  shall  return  when 
we  come  to  consider  the  nervous  mechanism  of  respiration. 


Pleural  Cannula.  B, 
a  line  of  small  spurs 
which,  after  the  can- 
nula C  has  been 
pushed  without  ad- 
mission of  air  through 
an  intercostal  space 
into  the  pleural 
cavity,  stick  in  the 
parietal  pleura  and 
securely  fasten  the 
cannula.  Traction 
being  made  on  the 
cannula,  a  ligature  is 
tied  at  L  around  the 
protruding  tissue  for 
greater  security.  S. 
side-tube  by  whichthe 
cannula  is  connected 
with  a  manometer  or 
tambour. 


234 


RESPJRA  TION 


It  cannot  fail  to  be  observed  that  to  a  great  extent  the  rate  of 
respiration  is  affected  by  the  same  circumstances  as  the  frequency 
of  the  heart  (p.  107),  and  in  the  same  direction.  And,  indeed,  in 
health,  these  two  physiological  quantities,  amid  all  their  absolute 
variations,  maintain  to  each  other  a  fairly  constant  ratio  (i  to  4  or 

I  to  5  in  man).  Even  in  many  diseases 
this  proportion  remains  tolerably 
stable,  although  in  others  it  is  dis- 
turbed. 

The  total  quantity  of  air  expired,  or, 
what  comes  to  the  same  thing,  the 
alteration  in  the  capacity  of  the  chest 
during  expiration,  can  be  measured  by 
means  of  a  gas-meter  or  of  a  spiro- 
meter (Fig.  114),  which  consists  of  an 
inverted  graduated  glass  cyhnder  dip- 
ping by  its  open  mouth  into  water 
and  balanced  by  weights.  The  vessel 
is  sunk  till  it  is  full  of  water,  the  air 
being  allowed  to  escape  by  a  cock. 
The  expired  air  is  now  permitted  to 
enter  it  through  a  tube,  and  displaces 
some  of  the  water.  The  spirometer 
is  adjusted  so  that  the  level  of  the 
water  inside  and  outside  is  the  same, 
and  then  the  volume  of  air  contained  in  it  is  read  off.  This  gives 
the  volume  of  the  expired  air  at  atmospheric  pressure.  Similarly, 
by  breathing  air  from  the  spirometer  the  amount  inspired  can  be 
measured  (p.  297). 

From  400  to  500  cc.  of  air*  are  taken  in  and  given  out  at  each 
respiration  in  quiet  breathing.  This  is  called  tidal  air.  It  amounts 
to  35  pounds  by  weight 
in  twenty-four  hours, 
or  enough  to  fill,  at 
atmospheric  pressure, 
a  cubical  box  with  a 
side  of  8  feet.  With 
the  deepest  possible  in- 
spiration room  can  be 
made  for  2,000  cc.  more ;  this  is  called  complemental  air.  By  a  forced 
expiration  1,500  cc.  can  be  expelled  besides  the  tidal  air ;  and  to  this 

*  The  average  for  81  healthy  students,  with  an  average  bod 3'- weight  of 
66  kilos,  was  460  cc,  or  7  cc  per  kilo.  In  4  new-born  children  the  tidal  air 
varied  from  20  to  30  cc,  and  from  76  to  7"3  cc.  per  kilo,  which  is  not  very 
different  from  the  amount  in  the  adult.  The  pulmonary  ventilation  must 
therefore  be  far  more  rapid  in  the  child,  since  its  respiratory  frequency  is  so 
much  greater. 


Fig.  114. — Diagram  of  Spirometer. 
A,  vessel  filled  with  water.  B, 
glass  cylinder  with  scale  C, 
swung  on  pulleys  and  counter- 
poised by  weights  W.  D,  tube 
for  breathing  through. 


lital    \WmM/m  Complemental  air 


Fig.  115. — Diagram  to  illustrate  the  Relative  Amount 
of  Complemental,  Tidal,  Supplemental,  and  Residual 
Air. 


MECHANICAL  PHENOMENA  OF  EXTERNAL  RESPIRATION      235 

quantity  the  name  of  supplemental  or  reserve  air  has  been  given. 
After  the  deepest  expiration  thc^e  always  remains  1,000  to  1,200  c.c. 
of  air  in  the  lungs  (Durig),  and  this  is  called  the  residual  air.  After 
a  normal  expiration  following  a  normal  inspiration  the  lungs  still 
contain  stationary  air  to  the  amount  of  about  2,500  c.c. 

The  term  vital  or  respiratory  capacity  is  applied  to  the  quantity 
of  air  which  can  be  expelled  by  the  deepest  expiration  following  the 
deepest  inspiration,  and  amounts  in  an  adult  of  average  height  to 
3,500  or  4,000  c.c.  The  maximum  quantity  of  air  which  the  lungs 
can  contain  is  evidently  equal  to  vital  capacity  plus  residual  air. 
At  one  time  the  vital  capacity  was  thought  to  be  capable  of  affording 
valuable  information  in  the  diagnosis  of  chest  diseases;  but  little 
stress  is  now  laid  upon  it,  as  it  varies  from  so  many  causes.  For 
instance,  it  can  be  increased  by  practice  with  the  spirometer.  It  is 
greater  in  mountaineers  than  in  +he  inhabitants  of  lowland  plains. 

It  is  clear  from  the  figures  we  have  given  that  in  ordinary  breath- 
ing only  a  small  proportion  of  the  air  in  the  lungs  comes  in  direct  at 
each  inspiration  from  the  atmosphere,  and  only  a  small  proportion 
escapes  into  the  atmosphere  at  each  expiration.  The  greater  part 
of  the  air  in  the  lungs  is  simply  moved  a  little  farther  from  the  upper 
respiratory  passages,  or  a  little  nearer  them;  and  fresh  oxygen 
reaches  the  alveoli,  as  carbon  dioxide  leaves  them,  mainly  by  diffu- 
sion, aided  by  convection  currents  due  to  inequalities  of  temperature, 
and  to  the  churning  which  the  alternate  expansion  and  shrinking 
of  the  lungs,  and  the  pulsations  of  their  arteries,  must  produce. 
But  that  some  of  the  tidal  air  strikes  right  down  to  the  alveoli  is 
evident  enough.  For  the  respiratory  '  dead  space  ' — that  is,  the 
capacity  of  the  upper  air-passages  and  the  bronchial  tree  down  to 
the  infundibula — is  only  140  c.c,  or  one-third  of  the  amount  of  the 
tidal  air  (Zuntz,  Loewy).  There  is  no  direct  way  of  determining 
whether  any  respiratory  exchange  goes  on  through  the  walls  of  the 
upper  air-passages.  But  by  indirect  methods  it  has  been  estimated 
that  about  30  per  cent,  of  the  volume  of  the  tidal  air  is  pure  air 
(Haldane  and  Priestley).  This,  of  course,  corresponds  to  the  '  effec- 
tive '  dead  space.  Taking  the  average  tidal  air  at  460  c.c.  (p.  234), 
it  is  clear  that  the  effective  corresponds  very  closely  with  the  ana- 
tomical dead  space — that  is  to  say,  the  respiratory  function  of  the 
air-passages  above  the  point  where  the  infundibula  are  given  off  is 
negligible.  Although  such  calculations  can  only  be  approximately 
correct,  the  agreement  is  of  interest.  The  immense  extent  of  the 
pulmonary  surface,  and  the  extreme  thinness  of  the  layer  of  blood 
in  the  capillaries  of  the  lungs  and  of  the  alveolar  walls,  facilitate 
the  interchange  between  the  gases  of  the  blood  and  the  gases  of  the 
alveoli. 

The  Amount  and  Variations  of  the  Intrathoracic  Pressure. — In  the 
deepest  expiration  tlie  lungs  are  never  completely  collapsed;  their 


236 


RESPIRA  TION 


elastic  fibres  are  still  stretched;  and  the  tension  of  these  acts  in  the 
opposite  direction  to  the  external  atmospheric  pressure,  and  dimin- 
ishes by  its  amount  the  pressure  inside  the  thoracic  cavity.  In  the 
dead  body  Bonders  measured  the  value  of  this  tension,  and  there- 
fore of  the  negative  pressure  of  the  thorax,  by  tying  a  manometer 
into  the  trachea,  and  then  causing  the  lungs  to  collapse  by  opening 
the  chest  It  varied  from  7-5  mm.  of  mercury  in  the  expiratory 
position  to  9  mm.  in  the  inspiratory.  So  far  as  can  be  judged  from 
observations  made  on  persons  suffering  from  various  diseases  of  the 


Fi„  it6— Variations  of  Intrathoracic  Pressure.  Upper  curve,  carotid  blood-pres- 
sure  (dog);  lower  curve,  intrapleural  pressure.  At  42  tlie  trachea  was  closed; 
the  blood-pressure  curve  shows  the  rise  of  asphyxia,  and  the  intrapleural  curve, 
greatly  exaggerated  pressure  variations  due  to  the  strong  and  slow  but  abortive 
respirations. 

respiratory  organs,  the  alterations  during  ordinary  breathing  do  not 
amount  to  more  than  3  or  4  mm.  of  mercury.  But  when  an  attempt 
is  made  in  the  dead  body  to  imitate  a  deep  inspiration  by  making 
traction  on  the  chest-walls  so  as  to  expand  the  lungs,  the  intra- 
thoracic pressure  may  fall  to  -30  mm.  of  mercury;  and  in  a  hving 
rabbit,  during  a  deep  natural  inspiration,  a  pressure  of  -20  mm. 

has  been  seen. 

The  reason  why  the  lungs  collapse  when  the  chest  is  opened  is 
that  the  pressure  is  now  equal  on  the  pleural  and  alveolar  surfaces, 
being  in  both  cases  that  of  the  atmosphere.     There  is  therefore 


MECHANICAL  PHENOMENA   OF  EXTERNAL  RESPIRATION     237 

nothing  to  oppose  the  elasticity  of  the  lungs,  which  tends  to  con- 
tract them.  So  long  as  the  chest  is  unopened,  the  pressure  on  the 
pleural  surface  of  the  lungs  is  less  than  that  on  the  alveolar  surface, 
and  the  elastic  tension  can  only  cause  them  to  shrink  until  it  just 
balances  this  difference. 

In  intra-uterine  life,  and  in  stillborn  children  who  have  never 
breathed,  the  lungs  are  completely  collapsed  (atelectatic),  and  there 
is  no  negative  intrathoracic  pressure.  They  are  kept  in  this  con- 
dition by  adhesion  of  the  walls  of  the  bronchioles  and  alveoh.  If 
the  lungs  have  been  once  inflated,  this  adhesion  ceases  to  act,  and 
they  never  completely  collapse  again. 

Amount  and  Variations  of  the  Respiratory  or  Intrapulmonary 
Pressure. ^As  we  have  already  remarked,  the  pressure  in  the  alveoli 
and  air- passages  is  less  than  that  of  the  atmosphere  while  the  in- 
spiratory movement  is  going  on,  greater  than  that  of  the  atmosphere 
during  the  expiratory  movement,  and  equal  to  that  of  the  atmo- 
sphere when  the  chest-walls  are  at  rest.  When  the  external  air- 
passages  are  closed — e.g.,  by  connecting  a  manometer  with  the 
mouth  and  pinching  the  nostrils — the  greatest  possible  variations 
of  pressure  are  produced.  In  the  deepest  inspiration  under  these 
conditions  a  negative  pressure  of  about  75  mm.  of  mercury  {i.e.,  a 
pressure  less  than  that  of  the  atmosphere  by  this  amount)  has  been 
found,  and  in  deep  expiration  a  somewhat  greater  positive  pressure* 
(Practical  Exercises,  p.  298). 

But  with  ordinary  breathing,  the  variations  of  pressure  as 
measured  by  this  method  do  not  exceed  5  to  10  mm.  of  mercury 
above  or  below  the  pressure  of  the  atmosphere. 

When  the  external  openings  are  not  obstructed,  as,  for  example, 
when  the  lateral  pressure  is  taken  in  the  trachea  of  an  animal  by 
means  of  a  cannula  with  a  side-tube  connected  with  a  manometer, 
still  smaller,  and  doubtless  truer,  values  have  been  found  (2-3  mm. 
of  mercury  as  the  positive  expiratory  pressure  and  i  mm.  as  the 
negative  inspiratory  pressure  in  dogs).  But  since  the  respiratory 
passages  are  abruptly  narrowed  at  the  glottis,  the  variations  of 
pressure  must  be  greater  below  than  above  it,  and  in  general  they 
must  increase  with  the  distance  from  that  orifice,  being  greater,  for 
instance,  in  the  alveoli  than  in  the  bronchi. 

The  mechanical  phenomena  of  respiration  having  been  described, 
it  might  seem  logical  to  consider  next  the  nervous  mechanism  by 
which  the  respiratory  movements  are  controlled;  but  the  regulation 
of  the^e  movements  through  the  nervous  system  is  in  so  important 
a  degree  a  chemical  regulation  that  it  cannot  be  properly  understood 

♦  The  maximum  negative  pressure  in  deepest  inspiration  averaged  for  49 
students  -73  mm.  (highest  observation  —137  mm.)  of  mercury;  the  maxi- 
mum positive  pressure  in  deepest  expiration,  +  80  mm.  (highest  observation 
4-140  mm.). 


238  RESPIRA  TION 

without  some  knowledge  of  the  chemical  changes  in  the  blood 
associated  with  external  and  internal  respiration.  We  therefore 
pass  to  the  consideration  of — 


Section  III. — The  Chemistry  of  External  Respiration. 

Our  knowledge  of  this  subject  has  been  entirely  acquired  in  the 
last  200  years,  and  chiefly  in  the  last  century. 

Boyle  showed  by  means  of  the  air-pump  that  animals  die  in  a 
vacuum,  and  Bernoiiilli  that  fish  cannot  live  in  water  from  which 
the  air  has  been  driven  out  by  boihng. 

Mayow,  of  Oxford,  seems  to  a  considerable  extent  to  have  antici- 
pated Black,  who  in  1757  demonstrated  the  presence  of  carbonic 
acid  (carbon  dioxide)  in  expired  air  by  the  turbidity  which  it  causes 
in  hme-water. 

A  fundamental  step  was  the  discovery  of  oxygen  by  Priestley  in 
1771,  and  his  proof  that  the  venous  blood  could  be  made  crimson, 
like  arterial,  by  being  shaken  up  with  oxygen. 

Lavoisier  discovered  the  composition  of  carbonic  acid,  and  applied 
his  discovery  to  the  explanation  of  the  respiratory  processes  in 
animals,  the  heat  of  which  he  showed  to  be  generated,  like  that  of  a 
candle,  by  the  union  of  carbon  and  oxygen.  He  made  many  further 
important  experiments  on  respiration,  publishing  some  of  his  results 
in  1789,  when  the  French  Revolution,  in  which  he  was  to  be  one  of 
the  most  distinguished  victims,  was  breaking  out.  He  made  the 
mistake,  however,  of  supposing  that  the  oxidation  of  the  carbon 
takes  place  in  the  blood  as  it  passes  through  the  lesser  circulation. 

That  some  carbon  dioxide  is  formed  in  the  lungs  there  is  no  reason 
to  doubt,  and  the  quantity  may  even  be  considerable.  But  that 
they  are  not  the  chief  seat  of  oxidation  was  sufficiently  proved  as 
soon  as  it  was  known  that  the  blood  which  comes  to  them  from  the 
right  heart  is  rich  in  carbon  dioxide,  while  the  blood  which  leaves 
them  through  the  pulmonary  veins  is  comparatively  poor. 

There  are  two  main  lines  on  which  research  has  gone  in  trying  to 
solve  the  chemical  problems  of  respiration:  (i)  The  analysis  and 
comparison  of  the  inspired  and  expired  air,  or,  in  general,  the  in- 
vestigation of  the  gaseous  exchange  between  the  blood  and  the  air 
in  the  lungs.  (2)  The  analysis  and  comparison  of  the  gases  of 
arterial  and  venous  blood,  of  the  other  liquids,  and  of  the  solid 
tissues  of  the  body,  with  a  view  to  the  determination  of  the  gaseous 
exchange  between  the  tissues  and  the  blood.  We  shall  take  these 
up  as  far  as  possible  in  their  order. 

The  methods  which  have  been  used  for  comparing  the  composi- 
tion of  inspired  and  expired  air  and  estimating  the  respiratory  ex- 
change are  very  various. 


THE  CHEMISTRY  OF  EXTERNAL  RESPIRATION  239 

(i)  Breathing  into  one  spirometer  and  out  of  another,  the  inspired 
and  expired  air  being  directed  by  valves.  The  contents  of  the  spiro- 
meters are  analyzed  at  the  end  of  the  experiment  (Speck).  In  the 
arrangement  oi  Zuntz  and  Geppcrt,  instead  of  the  whole  of  the  expired 
air,  a  sample  is  collected  for  analysis  during  the  entire  duration  of  the 
experiment,  while  the  total  volume  expired  is  measured  by  a  gas-meter. 
This  is  a  very  convenient  method  for  observations  on  man,  especially 
in  disease,  but  each  experiment  can  only  be  carried  on  at  most  for 
fifteen  to  twenty  minutes. 

(2)  A  small  apparatus,  much  on  the  same  principle,  was  used  for 
rabbits  by  Pfliiger  and  his  pupils.  A  cannula  in  the  trachea  was  con- 
nected with  a  balanced  and  self-adjusting  spirometer  containing  oxygen, 
and  the  inspired  and  expired  air  separated  by  potassium  hydroxide 
valves,  which  absorbed  the  carbon  dioxide.  The  amount  of  oxygen 
used  could  be  read  off  on  the  spirometer,  and  the  amount  of  carbon 
dioxide  produced  estimated  in  the  liquid  of  the  valves. 

(3)  Elaborate  arrangements,  such  as  Pettenkofer's  great  respiration 
app;iratus,  and  the  still  larger  and  more  ef&cient  modifications  of  it 
constructed  since  his  time,  in  which  a  man,  or  even  several  men,  can 
remain  for  an  indefinite  period,  working,  eating,  and  sleeping.  Air  is 
drawn  out  of  the  chamber  by  aa  engine,  its  volume  being  measured 
by  a  gas-meter.  But  as  it  would  be  far  too  troublesome  to  analyze 
the  whole  of  the  air,  a  sample  stream  of  it  is  constantly  drawn  off,  which 
also  passes  through  a  gas-meter,  through  drydng-tubes  containing 
sulphuric  acid,  and  through  tubes  filled  with  baryta  water.  The  baryta 
solution  is  titrated  to  determine  the  quantity  of  carbon  dioxide ;  the 
increase  in  weight  of  the  drying  tubes  gives  the  quantity  of  aqueous 
vapour.  A  similar  sample  stream  of  the  air  before  it  passes  into  the 
chamber  is  treated  exactly  in  the  same  way,  and  from  the  data  thus  got 
the  quantity  of  carbon  dioxide  and  aqueous  vapour  given  off  can  readily 
be  ascertained.  The  oxy'^gen  can  be  calculated,  as  the  difference  be- 
tween the  final  body-weight  and  the  original  body-weight  plus  the 
weight  of  the  carbon  dioxide  and  water  eliminated,  but  may  also  be 
directly  estimated  by  special  methods. 

{4)  Haldane  and  Pembrey  have  elaborated  a  gravimetric  method, 
which  is  very  suitable  for  small  animals.  It  depends  upon  the  absorp- 
tion of  carbon  dioxide  by  soda  lime.  (See  Practical  Exercises,  p.  299.) 
In  Atwater's  so-called  respiration  calorimeter,  which  will  be  referred  to 
again  under  '  Animal  Heat,'  and  by  which,  not  only  the  gaseous  metab- 
olism, but  the  heat  production  can  be  measured  in  man,  the  carbon 
dioxide  is  estimated  in  the  same  way. 

Inspired  and  Expired  Air. — The  expired  air  is  at  or  near  the  body 
temperature,  and  is  saturated  with  watery  vapour.  In  ordinary 
breathing  it  contains  about  4  per  cent,  of  carbon  dioxide,  while  the 
inspired  air  only  contains  a  trace.  The  expired  air  contains  16  or 
17  per  cent,  of  oxygen,  the  inspired  air  about  21  per  cent.  The 
percentage  of  carbon  dioxide  in  the  alveolar  air  is,  of  course,  greater 
than  in  the  ordinary  expired  air,  since  the  relatively  pure  air  of  the 
dead  space  constitutes  a  substantial  fraction  of  the  tidal  air.  The 
carbon  dioxide  percentage  in  the  alveolar  air  at  the  end  of  expira- 
tion, with  the  body  at  rest,  is  remarkably  constant  in  one  and  the 
same  individual  at  constant  atmospheric  pressure  (p.  261).  There 
are  in  addition  in  expired  air  small  quantities  of  hydrogen  and  marsh- 


240  RESPIRATION 

gas  derived  from  the  alimentary  canal,  either  directly  from  eructa- 
tion or  after  absorption  into  the  blood.  Sometimes  a  trace  of 
ammonia  can  be  detected  in  the  air  of  expiration,  but  this  is  due  to 
decomposition  of  proteins  taking  place  in  the  mouth,  especially  in 
carious  teeth,  or  in  the  air-passages  and  lungs  in  disease  of  these 
organs.  It  has  indeed  been  shown  that  the  lungs  are  practically 
impermeable  for  ammonia.  Expired  air  is  entirely  free  from  float- 
ing matter  (dust),  which  is  always  present  in  the  inspired  air.  The 
volume  of  the  expired  air,  owing  to  its  higher  temperature  and  ex- 
cess of  watery  vapour,  is  somewhat  greater  than  that  of  the  inspired 
air,  but  if  it  be  measured  at  the  temperature  and  degree  of  satura- 
tion of  the  latter,  the  volume  is  somewhat  less.  Since  the  oxygen 
of  a  given  quantity  of  carbon  dioxide  would  have  exactly  the  same 
volume  as  the  carbon  dioxide  itself  at  a  given  temperature  and 
pressure,  it  is  clear  that  the  deficiency  is  due  to  the  fact  that  all  the 
oxygen  which  is  taken  up  in  the  lungs  is  not  given  off  as  carbon 
dioxide.  Some  of  it,  going  to  oxidize  hydrogen,  reappears  as  water. 
A  small  amount  of  it  unites  with  the  sulphur  of  the  proteins  (p.  478). 
Respiratory  Quotient. — The  quotient  of  the  volume  of  oxygen 
given  out  as  carbon  dioxide  by  the  volume  of  oxygen  taken  in  is 
the  respiratory  quotient.  It  shows  what  proportion  of  the  oxygen 
is  used  to  oxidize  carbon.  It  may  approach  unity  on  a  carbo-hydrate 
diet  which  contains  enough  oxygen  to  oxidize  all  its  own  hydrogen 
to  water.  With  a  diet  rich  in  fat  it  is  least  of  all;  with  a  diet  of 
lean  meat  it  is  intermediate  in  amount.  For  ordinary  fat  contains 
no  more  than  one-sixth,  and  proteins  not  one-half,  of  the  oxygen 
needed  to  oxidize  their  hydrogen  (p.  608).  In  man  on  a  mixed  diet 
the  respiratory  quotient  may  be  taken  as  0-8  or  0-9.  So  long  as  the 
type  of  respiration  is  not  changed,  the  respiratory  quotient  may 
remain  constant  for  a  wide  range  of  metabolism.  In  hibernating 
animals,  however,  the  respiratory  quotient  may  become  very  small 
during  winter  sleep  (as  low  as  0-25),  both  the  output  of  carbon 
dioxide  and  the  consumption  of  oxygen  falhng  enormously,  but 
the  former  in  general  more  than  the  latter.  This  has  been  explained 
on  the  assumption  that  oxygen  is  stored  away  in  winter  sleep  in  the 
form  of  incompletely  oxidized  substances.  On  the  other  hand,  in 
dyspnoea  accompanying  muscular  exertion  the  respiratory  quotient 
has  been  found  as  high  as  i'2.  It  must  be  remembered  that  even 
a  voluntary  increase  in  the  respiratory  movements  causes  an  imme- 
diate temporary  increase  in  the  respiratory  quotient,  owing  to  the 
'  washing  out  '  of  carbon  dioxide  from  the  blood  and  tissues.  This 
change  has  no  metabolic  significance.  Indeed,  the  determination 
of  the  respiratory  quotient  for  short  periods  has  only  a  limited 
value,  and  such  observations  must  be  interpreted  with  great  care. 
In  starvation  the  respiratory  quotient  diminishes,  the  production 
of  carbon  dioxide  falling  off  at  a  greater  rate  than  the  consumption 


THE  CHEMISTRY  OF  EXTERNAL  RESPIRATION  24! 

of  oxygen,  for  the  starving  organism  lives  on  its  own  fat  and  pro- 
teins, and  has  only  a  trifling  carbo-hydrate  stock  to  draw  upon. 
In  a  diabetic  patient,  fed  on  a  diet  of  fat  and  protein  alone,  the 
respiratory  quotient  was  only  o-6  to  07,  just  as  in  a  starving  man. 
Total  Respiratory  Exchange. — The  amount  of  oxygen  absorbed  in 
a  man  at  rest  has  been  determined  under  certain  conditions  as  about 
0-29  gramme  per  hour,  and  the  discharge  of  carbon  dioxide  as  about 
0*33  gramme  per  hour  per  kilogramme  of  body-weight.  In  an 
average  man  weighing  70  kilos  the  mean  production  of  carbon 
dioxide  is  about  800  grammes  (400  litres)  in  twenty-four  hours,  and 
the  mean  consumption  of  oxygen  about  700  grammes  (490  litres). 
But  there  are  very  great  variations  depending  upon  the  state  of  the 
body  as  regards  rest  or  muscular  activity  and  on  other  circum- 
stances. In  hard  work  the  production  of  carbon  dioxide  was  found 
to  rise  to  nearly  1,300  grammes,  and  in  rest  to  sink  to  less  than 
700  grammes,  the  consumption  of  oxygen  in  the  same  circumstances 
increasing  to  nearly  1,100  grammes  and  diminishing  to  600  grammes. 
In  rest,  in  moderate  exertion,  and  in  hard  work,  the  production  of 
carbon  dioxide  was  found  to  be  nearly  proportionate  to  the  numbers 
2,  3,  and  6  respectively.  When  unaccustomed  work  is  performed, 
the  increase  in  the  carbon  dioxide  output  (and  oxygen  intake)  may 
be  much  greater.  With  training  it  diminishes.  In  a  case  of  diabetes 
the  consumption  of  oxygen  was  50  per  cent,  greater  than  in  a  healthy 
man,  corresponding  to  the  higher  heat-equivalent  of  the  food  of 
the  diabetic  patient. 

Ventilation. — Taking  400  litres  per  twenty-four  hours,  or  17  litres 
per  hour,  as  the  mean  production  of  carbon  dioxide  by  an  average  male 
adult  at  rest  or  doing  only  light  work,  we  can  calculate  the  quantity  of 
fresh  air  which  must  be  supplied  to  a  room  in  order  to  keep  it  properly 
ventilated. 

It  has  been  found  that  when  the  carbon  dioxide  given  off  in  respiration 
amounts  to  no  more  than  2  parts  in  10,000  in  the  air  of  an  ordinary 
room,  the  air  remains  sweet.  When  the  carbon  dioxide  given  off  reaches 
4  parts  in  10,000,  the  room  feels  distinctly,  and  at  6  in  10,000  disagree- 
ably, close,  while  at  9  parts  in  10,000  it  is  oppressive  and  almo.st  in- 
tolerable. This  is  not  due  to  the  carbon  dioxide  as  such,  for  pure 
carbon  dioxide  added  alone  in  similar  proportions  to  the  air  of  a  room 
has  not  the  same  bad  effect,  and  the  amount  of  this  gas  is  only  taken 
as  an  index  of  the  extent  to  which  the  air  has  been  vitiated  by  some 
other  products  or  processes  connected  with  the  occupation  of  the 
room.  Very  often  the  mere  rise  of  temperature  in  a  crowded  and  ill- 
ventilated  space  is  sufficient  to  induce  disagreeable  symptoms,  especially 
as  it  is  inevitably  associated  with  an  i^icrease  in  the  humidity  of  the 
air,  which  reduces  the  capacity  of  the  body  to  cool  itself  by  increasing 
the  secretion  of  sweat.  Thus  it  has  been  found  that  persons  in  a 
respiratory  chamber  feel  quite  comfortable  with  only  moderate  ventila- 
tion when  the  carbon  dioxide  has  risen  to  i  per  cent.,  if  care  is  taken 
that  the  temperature  and  ^he  proportion  of  watery  vapour  do  not  rise 
too  high.  In  addition,  however,  it  has  been  supposed  by  some  that  a 
volatile  poison  exhaled  from  the  lungs  is  peculiarly  responsible  for  the 

'ft 


242  kESPIRA  TION 

evil  effects.  Certain  observers,  indeed,  alleged  that  the  condensed 
vapour  of  the  breath,  when  injected  into  rabbits,  produced  fatal  symp- 
toms. But  this  has  been  shown  to  be  erroneous;  and  the  most  careful 
experiments  have  failed  to  detect  in  the  air  expired  by  healthy  persons 
any  trace  of  such  a  poison.  It  has  therefore  been  suggested  that  the 
odour  and  some  of  the  other  ill-effects  of  a  close  room  are  due  to  sub- 
stances given  off  in  the  sweat  and  the  sebum,  and  allowed  by  persons 
of  uncleanly  habits  to  accumulate  on  the  skin,  and  also  to  the  products 
of  slow  putrefactive  processes  constantly  going  on,  under  favourable 
conditions,  on  the  walls,  floor,  or  furniture,  but  only  becoming  per- 
ceptible to  the  sense  of  smell  when  ventilation  is  insufficient.  In  a 
small,  newly-pamted  chamber,  presumably  free  from  such  impurities, 
it  was  not  until  the  carbon  dioxide  reached  3  to  4  per  cent.,  an  immensely 
greater  proportion  than  occurs  even  in  ver^^  badly  ventilated  rooms, 
that  marked  discomfort,  with  dyspnoea,  began  to  be  felt.  No  close 
odour  could  be  detected. 

Nevertheless,  experience  has  shown  that  it  is  a  good  working  rule  for 
ventilation  to  take  the  limit  of  permissible  respiratory  impurity  at 
2  parts  of  carbon  dioxide  per  10,000;  and  the  17  litres  of  carbon  dioxide 
given  off  in  the  hour  will  require  85,000  litres  (or  3,000  cubic  feet)  of 
air  to  dilute  it  to  this  extent.  This  is  the  average  quantity  required 
for  the  male  adult  per  hour.  For  men  engaged  in  active  labour,  as  in 
factories  or  mines,  twice  this  amount  may  not  be  too  much.  For 
women  and  children  less  is  required  than  for  men.  If  a  room  smells 
close,  it  needs  ventilation,  whatever  be  the  proportion  of  carbon  dioxide 
in  the  air.  It  must  be  remembered  that  in  permanently  occupied 
rooms  mere  increase  in  the  size  will  not  compensate  for  incomplete 
renewal  of  the  air,  although  it  may  be  easier  to  \'entilate  a  large  room 
than  a  small  one  without  causing  draughts  and  other  inconveniences. 
But  as  few  apartments  are  occupied  during  the  whole  twenty-four  hours, 
a  large  room  which  can  be  thoroughly  ventilated  in  the  absence  of  its 
inmates  has  a  distinct  advantage  over  a  small  one  in  its  great  initial 
stock  of  fresh  air.  The  cubic  space  per  head  in  an  ordinary  dweUing- 
house  should  be  not  less  than  28  cubic  metres  or  1,000  cubic  feet. 

The  quantity  of  carbon  dioxide  given  off  (and  of  oxygen  consumed) 
is  not  only  affected  by  muscular  work,  but  also  by  everything  which 
influences  the  general  metabolism.  In  males  it  is  greater  on  the 
average  than  in  females  (in  the  latter  there  is  a  temporary  increase 
during  pregnancy),  but  for  the  same  body- weight  and  under  similar 
external  conditions  there  is  no  difference  between  the  sexes.  The 
gaseous  exchange  is  greater  in  proportion  to  the  body-weight  in  the 
child  than  in  the  adult.  This  depends  largely  on  the  fact  that, 
other  things  being  equal,  the  metabolism  is  relatively'  to  the  body- 
weight  more  active  in  a  small  than  in  a  large  organism,  since 
the  surface  (and  therefore  the  heat  loss)  is  relatively  greater  in  the 
former.  But  it  has  been  shown  that  even  in  proportion  to  the 
surface  the  metabolism  is  greater  in  youth  than  in  adult  life,  and 
greater  in  the  vigorous  adult  than  in  the  old  man.  So  that  the  age 
of  the  organism  has  an  influence  apart  from  the  extent  of  surface. 
The  taking  of  food  increases  the  gaseous  exchange,  partly  from  the 
increased  mechanical  and  chemical  work  performed  by  the  ali- 
mentary canal  and  the  digestive  glands.     But  that  this  is  not  the 


THE  CHEMISTRY  OF  EXTERNAL  RESPIRATION 


243 


Sole  cause  of  the  increase  is  shown  by  the  fact  that  it  varies  w\th 
different  kinds  of  food  to  a  greater  extent  than  can  be  explained 
by  differences  in  the  ease  with  which  they  are  digested.  For  in- 
stance, maize  produces  a  much  greater  increase  than  oats  when 
given  in  equal  amount,  and  a  protein  diet  a  greater  increase  than  a 
diet  of  carbo-hydrate  or  fat.  Sleep  diminishes  the  production  of 
carbon  dioxide  partly  because  the  muscles  are  at  rest,  but  also  to 
some  extent  because  the  external  stimuh  that  in  waking  life  excite 
the  nerves  of  special  sense  are  absent  or  ineffective.  Even  a  bright 
light  is  said  to  cause  an  increase  in  the  aimount  of  carbon  dioxide 
produced  and  of  oxygen  consumed;  but  probably  only  by  increasing 
muscular  movements,  including  the  movements  of  respiration. 
The  external  temperature  also  has  an  influence.  In  poikilothermal 
animals  (such  as  the  frog),  the  temperature  of  which  varies  with 
that  of  the  surrounding  medium,  the  production  of  carbon  dioxide, 
on  the  whole,  diminishes  as  the  external  temperature  falls,  and 
increases  as  it  rises.  In  homoiothermal  animals,  that  is,  animals 
with  constant  blood  temperature,  external  cold  increases  the  pro- 
duction of  carbon  dioxide  and  the  consumption  of  oxygen.  But  if 
the  connection  of  the  nervous  system  with  the  striated  muscles  has 
been  cut  out  by  curara,  the  warm-blooded  animal  behaves  hke  the 
cold-blooded  (Pfluger  and  his  pupils  in  guinea-pig  and  rabbit). 
These  interesting  facts  will  be  returned  to  under  '  Animal  Heat.' 

Cold-blooded  animals  produce  far  less  carbon  dioxide,  and  con- 
sume far  less  oxygen,  per  kilo  of  body-weight  than  warm-blooded. 

The  following  table  shows  the  relation  between  the  body-weight 
and  the  excretion  of  carbon  dioxide  in  man : 


Age. 

Weight  in  Kilos. 

CO2  excreted  per  Kilo 
per  Hour. 

[58 

84-6             i 

0-41  gramme 

44 

76-5             ' 

0-48 

Male 

35 

65 

0-51 

28 

82 

0-49 

16 

57-7          i 

0-59 

I  9-t> 

22 

0*92 

1-66 
Female-  „ 

1 
66-9 

0-39 

53-9 

0'54 

19 

55-7          ' 

0-45 

.10 

-3             ! 

0-83 

The  next  table  illustrates  the  difference  in  the  intensity  of  metab- 
olism in  different  kinds  of  animals,  a  difference,  however,  largely 
dependent  upon  relative  size: 


244 


RESPIRATION 


Oxygen  absorbed  per 

Carbon  Dioxide  given  off 

Kilo  per  Hour. 

per  Kilo  per  Hour. 

Respiratory  Quotient 

Animal. 

CO2      Oo  (in  CO2) 
0.,  °'          O2        • 

In  Grms. 

In  C.C. 

In  Grms. 

In  C.C. 

Greenfinch    - 

13-000 

9091 

13-590 

6909 

0-76 

Hen      - 

1-058 

740 

1-3^7 

675 

0-91 

Dog      - 

1-303 

911 

1-3^5 

674 

074 

Rabbit 

0-987 

690 

1-244 

632 

0-91 

Sheep  - 

0-490 

343 

0-671 

.341 

0-99 

Boar     - 

0-391 

273 

0-443 

225 

0-82 

Frog     - 

0-105 

73-4 

0-113 

57-7 

0-78 

Crayfish 

0-054 

38 

0-064 

32-7 

0-86 

Forced  respiration,  although  it  will  temporarily  increase  the 
quantity  of  carbon  dioxide  given  off  by  the  lungs,  and  thus  raise 
for  a  short  time  the  respiratory  quotient,  does  not  sensibly  affect 
the  production;  it  is  only  the  store  of  already  formed  carbon  dioxide 
in  the  body  which  is  drawn  upon.  The  amount  of  oxygen  taken 
up  is  little  altered  by  changes  in  the  movements  of  respiration. 
Within  wide  limits  the  oxygen  consumption  of  the  organism  is  in- 
dependent of  the  supply  of  oxygen  offered  to  it. 

How  it  is  that  the  depth  of  the  respiration  may  affect  the  rate  at 
which  carbon  dioxide  is  eliminated,  we  can  only  understand  when 
we  have  examined  the  process  by  which  the  gaseous  interchange 
between  the  blood  and  the  air  of  the  alveoli  is  accomplished;  and 
before  doing  this  it  is  necessary  to  consider  the  condition  of  the 
oxygen  and  carbon  dioxide  in  the  blood. 


Section  IV. — The  Gases  of  the  Blood. 

Physical  Introduction. — Matter  may  be  assumed  to  be  made  up  of 
molecules  beyond  which  it  cannot  be  divided  without  altering  its  essen- 
tial character.  A  molecule  may  consist  of  two  or  more  particles  of 
matter  (atoms)  bound  to  each  other  by  chemical  links.  The  kinetic 
theory  of  matter  supposes  the  molecules  of  a  substance  to  be  in  constant 
motion,  frequently  colliding  with  each  other,  and  thus  having  the  direc- 
tion of  their  motion  changed. 

In  a  gas  the  mean  free  path,  that  is,  the  average  distance  which  a 
molecule  travels  without  striking  another,  is  comparatively  long,  and 
far  more  time  is  passed  by  any  molecule  without  an  encounter  than  is 
taken  up  with  collisions.  Although  the  average  velocity  of  the  mole- 
cules is  very  great,  these  collisions  will  produce  all  sorts  of  differences 
in  the  actual  velocity  of  different  molecules  at  any  given  time.  Some 
will  be  moving  at  a  greater,  some  at  a  slower  rate,  than  the  average; 
while  some  may  be  for  a  moment  at  rest.  If  the  gas  is  in  a  closed 
vessel,  the  molecules  will  be  constantly  striking  its  sides  and  rebounding 
from  them.  If  a  very  small  opening  is  made  in  the  vessel,  some  mole- 
cules will  occasionally  hit  on  the  opening  and  escape  altogether.  If  the 
opening  is  made  larger,  or  the  experiment  continued  for  a  longer  time 


THE  GASES  OF  THE  BLOOD  245 

with  the  small  opening,  all  the  molecules  will  in  course  of  time  have 
passed  out  of  the  vessel  into  the  air,  while  molecules  of  the  ox^'gen, 
nitrogen,  and  argon  of  the  air  will  have  passed  in.  In  a  gas,  then,  not 
enclosed  by  impenetrable  boundaries,  there  is  no  restriction  on  the  path 
which  a  molecule  may  take,  no  tendency  for  it  to  keep  within  any  limits. 

When  two  chemically  indifferent  gases  are  placed  in  contact  with  each 
other,  diffusion  will  go  on  till  they  are  uniformly  mixed.  The  diffusion 
of  gases  may  be  illustrated  thus.  Suppose  we  have  a  perfectly  level 
and  in  every  way  uniform  field  divided  into  two  equal  parts  by  a  visible 
but  intangible  line,  the  well-known  whitewash  line,  for  instance.  On 
one  side  of  the  line  place  500  blind  men  in  green,  and  on  the  other  500 
blind  men  in  red.  At  a  given  signal  let  them  begin  to  move  about  in 
the  field.  Some  of  the  men  in  green  will  pass  over  the  line  to  the  '  red  ' 
side;  some  of  the  men  in  red  will  wander  to  the  '  green  '  side.  Some 
of  the  men  may  pass  over  the  line  and  again  come  back  to  the  side 
they  started  from.  But,  upon  the  whole,  after  a  given  interval  has 
elapsed,  as  many  green  coats  will  be  seen  on  the  red  side  as  red  coats 
on  the  green.  And  if  the  interval  is  long  enough  there  will  be  at  length 
about  250  men  in  red  and  250  in  green  on  each  side  of  the  boundary- 
line.  When  this  state  of  equilibrium  has  once  been  reached,  it  will 
henceforth  be  maintained,  for,  upon  the  whole,  as  many  red  uniforms 
will  pass  across  the  line  in  one  direction,  as  will  recross  it  in  the  other. 

In  a  liquid  it  is  very  different;  the  molecule  has  no  free  path.  In  the 
depth  of  the  liquid  no  molecule  ever  gets  out  of  the  reach  of  other 
molecules,  although  after  an  encounter  there  is  no  tendency  to  return  on 
the  old  path  rather  than  to  choose  any  other;  so  that  any  molecule 
may  wander  through  the  whole  liquid.  Although  the  average  velocitj- 
of  the  molecules  is  much  less  in  the  liquid  state  than  it  would  be  for 
the  same  substance  in  the  state  of  gas  or  vapour  (gas  in  presence  of  its 
liquid),  some  of  them  may  have  velocities  much  above  the  average. 
If  any  of  these  happen  to  be  moving  near  the  surface  and  towards  it, 
they  may  overcome  the  attraction  of  the  neighbouring  molecules  and 
escape  as  vapour.  But  if  in  their  further  wanderings  they  strike  the 
liquid  again,  they  may  again  become  bound  down  as  liquid  molecules. 
And  so  a  constant  interchange  may  take  place  between  a  liquid  and  its 
vapour,  or  between  a  liquid  and  any  other  gas,  until  the  state  of  equi- 
librium is  reached,  in  which  on  the  average  as  many  molecules  leave  the 
liquid  to  become  vapour  as  are  restored  by  the  vapour  to  the  liquid,  or  as 
many  molecules  of  the  dissolved  gas  escape  from  solution  as  enter  into  it. 

For  the  sake  of  a  simple  illustration,  let  us  take  the  case  of  a  shallow 
vessel  of  water  originally  gas-free,  standing  exposed  to  the  air.  It  will 
be  found  after  a  time  that  the  water  contains  the  atmospheric  gases  in 
certain  proportions — in  round  numbers,  about  j^^  of  its  volume  of 
oxygen  and  ^\j  of  its  volume  of  nitrogen  (measured  at  760  mm.  mercury 
and  0°  C). 

Now,  let  a  similar  vessel  of  gas-free  water  be  placed  in  a  large  airtight 
box  filled  with  air  at  atmospheric  pressure,  and  let  the  oxygen  be  all 
absorbed  before  the  water  is  exposed  to  the  atmosphere  of  the  box. 
The  latter  now  consists  practically  only  of  the  nitrogen  of  the  air.  and 
its  pressure  will  be  only  about  four- fifths  that  of  the  external  atmo- 
sphere. Nevertheless,  the  quantity  of  nitrogen  absorbed  by  the  water 
will  be  exactly  the  same  as  was  absorbed  from  the  air.  If  the  box 
was  completely  exhausted,  and  then  a  quantity  of  oxj'gen,  equal  to  that 
in  it  at  first,  introduced  before  the  water  was  exposed  to  it,  the  pressure 
would  be  found  to  be  only  about  one-fifth  that  of  the  external  atmo- 
sphere ;  but  the  quantity  of  oxygen  taken  up  by  the  water  would  be 
exactly  equal  to  that  taken  up  in  the  first  experiment. 


246 


RESPIRATION 


Two  well-known  physical  laws  are  illustrated  by  our  supposed  ex- 
periments: (i)  In  a  mixture  of  gases  which  do  not  act  chemically  on  each 
other  the  pressure  exerted  by  each  gas  {called  the  partial  pressure  of  the 
gas)  is  the  same  as  it  would  exert  if  the  others  were  absent.  (2)  The  quan- 
tity {mass)  of  a  gas  absorbed  by  a  liquid  which  does  not  act  chemically  upon 
it  is  proportional  to  the  partial  pressure  of  the  gas.  It  also  depends  upon 
the  nature  of  the  gas  and  of  the  liquid,  and  on  the  temperature,  increase 
of  temperature  in  general  diminishing  the  quantity  of  gas  absorbed. 
It  is  to  be  noted  that  when  the  volume  of  the  absorbed  gas  is  measured 
at  a  pressure  equal  to  the  partial  pressure  under  which  it  was  absorbed 
the  same  volume  of  gas  is  taken  up  at  every  pressure. 

The  volume  of  a  gas  (reduced  to  0°  C.  and  760  mm.  pressure)  physi- 
cally absorbed  or  dissolved  in  i  c.c.  of  a  liquid  exposed  to  the  gas  at 
760  mm.  pressure  is  called  the  absorption  coefficient  of  the  gas  in  that 
liquid.  The  following  table  from  Bohr  shows  the  absorption  coefficients 
of  the  three  gases  of  physiological  interest — oxygen,  nitrogen,  and 
carbon  dioxide  in  water,  blood-plasma,  whole  blood  and  blood-corpuscles 
at  the  body  temperature  (38°  C.) : 


Oxygen. 

Nitrogen. 

Carbon  Dioxide. 

Water 

Blood-plasma 

Blood  -         -         -         - 

Blood-cells  -         -         - 

0-0237 

0*023 

0*022 

o'oig 

0-OI22 
0'0I2 

o-oii 
o-oio 

O555 
0-541 
0-511 
0-450 

Suppose,  now,  that  a  vessel  of  water,  saturated  with  oxygen  and 
nitrogen  for  the  partial  pressures  under  which  these  gases  exist  in  the 
air,  is  placed  in  a  box  filled  with  pure  nitrogen  at  full  atmospheric  pres- 
sure. As  we  have  seen,  there  is  a  constant  interchange  going  on  between 
a  liquid  which  contains  gas  in  solution  and  the  atmosphere  to  which  it 
is  exposed.  Oxygen  and  nitrogen  molecules  will  therefore  continue  to 
leave  the  water;  but  if  the  box  is  large,  few  oxygen  molecules  will  find 
their  way  back  to  the  water,  and  ultimately  little  oxygen  will  remain 
in  it.  In  other  words,  the  quantity  of  oxygen  absorbed  by  the  water 
will  become  again  proportional  to  the  partial  pressure  of  oxygen,  which 
is  not  now  much  above  zero.  On  the  other  hand,  molecules  of  nitrogen 
will  at  first  enter  the  water  in  larger  number  than  they  escape  from  it, 
for  the  pressure  of  the  nitrogen  is  now  that  of  the  external  atmosphere, 
of  which  its  partial  pressure  was  formerly  only  four-fifths.  In  unit 
volume  of  the  gas  above  the  water  there  will  be  5  molecules  of  nitrogen 
for  every  4  molecules  in  the  same  volume  of  atmospheric  air.  There- 
fore, on  the  average  5  nitrogen  molecules  will  in  a  given  time  get  en- 
tangled by  liquid  molecules  for  every  4  which  came  within  their  sphere 
of  attraction  before.  On  the  whole,  then,  the  water  will  lose  oxygen 
and  gain  nitrogen,  while  the  atmosphere  of  the  airtight  box  will  gain 
oxygen  and  lose  nitrogen. 

In  the  case  of  water,  in  which  oxygen  and  nitrogen  are  absorbed 
solely  in  solution,  the  partial  pressures  of  these  gases  under  which  the 
water  was  originally  saturated  could,  of  course,  be  easily  calculated 
from  the  amount  dissolved  and  the  coefficient  of  absorption.  But 
supposing  that  these  partial  pressures  were  unknown,  it  is  evident  that 
by  exposing  it  to  an  atmosphere  of  known  composition,  and  afterwards 
determining  the  changes  produced  m  the  composition  of  that  atmo- 


T?IE  GASES  OF  THE  BLOOD 


247 


W^       fF^ 


Z) 


sphere  by  loss  to,  or  gain  from,  the  gases  of  the  water,  wc  could  find  out 
something  about  the  original  partial  pressures.  If,  for  example,  the 
quantity  of  oxygen  in  the  atmosphere  or  the 
chamber  was  increased,  we  could  conclude  that 
the  partial  pressure  of  oxygen  under  which  the 
water  had  been  saturated  was  greater  than 
that  in  the  chamber  at  the  beginning  of  the 
experiment.  And  if  we  found  that  with  a 
certain  partial  pressure  of  oxygen  in  the  atmo- 
sphere of  the  chamber  there  was  neither  gain 
nor  loss  of  this  gas,  we  might  be  sure  that  the 
partial  pressure  (the  temperature  being  sup- 
posed not  to  vary)  was  the  same  when  the 
water  was  saturated.  We  shall  see  later  on 
how  this  pnnciple  has  been  applied  to  deter- 
mine the  partial  pressure  of  oxygen  or  carbon 
dioxide  which  just  suffices  to  prevent  blood,  or 
any  other  of  the  lic|uids  of  the  body,  from 
losing  or  gaining  these  gases  when  they  are  not 
merely  dissolved,  but  also  combined  in  the 
form  of  dissociable  compounds.  This  pressure 
is  evidently  equal  to  that  exerted  by  the  gases 
of  the  liquid  at  its  surface,  which  is  sometimes 
called  their  '  tension  ' ;  for  if  it  were  greater, 
gas  would,  upon  the  whole,  pass  into  the  blood ; 
and  if  it  were  less,  gas  would  escape  from  the 
blood.  Thus,  the  tension  of  a  gas  in  sohition  in 
a  liquid  is  eqtial  to  the  partial  pressure  of  that 
gas  in  an  atmosphere  to  which  the  liquid  is  ex- 
posed, which  is  just  sufficient  to  prevent  gain  or 
loss  of  the  gas  by  the  liquid  (p.  256). 

The  following  imaginary  experiment  may 
further  illustrate  the  meaning  of  the  term  '  ten- 
sion '  of  a  gas  in  a  liquid  in  this  connection. 

Suppose  a  cylinder  filled  with  a  liquid  con- 
taining a  gas  in  solution,  and  closed  above  by 
a  piston  moving  airtight  and  without  friction, 
in  contact  with  the  surface  of  the  liquid  (Fig. 
117).  Let  the  weight  of  the  piston  be  balanced 
by  a  counterpoise.  The  pressure  at  the  sur- 
face of  the  liquid  is  evidently  that  of  the 
atmosphere.  Now,  let  the  whole  be  put  into 
the  receiver  of  an  air-pump,  and  the  air 
gradually  exhausted.  Let  exhau.stion  proceed 
until  gas  begins  to  escape  from  the  liquid  and 
lies  in  a  thin  layer  between  its  surface  and  the 
piston,  the  quantity  of  gas  which  has  become 
free  being  very  small  in  proportion  to  that 
still  in  solution.  At  this  point  the  piston  is 
acted  upon  by  two  forces  which  balance  each 
other,  the  pressure  of  the  air  in  the  receiver 
acting  downwards,  and  the  pressure  of  the  gas 
escaping  from  the  liquid  acting  upwards.  If 
the  pressure  in  the  receiver  is  now  slightly 
increased,  the  gas  is  again  absorbed.  Tlac  pressure  at  which  this  just 
happens,  and  against  which  the  piston  is  still  supported  by  the  impacts 
of  ga;  eous  molecules  flying  out  of  the  liquid   while  no  pressure  is  as  yet 


Fig.  117. — Imaginary  Ex- 
periment to  illustrate 
'  Tension '  of  a  Gas  in  a 
Liquid.  P,  frictionless 
piston;  L,  liquid  in  cy- 
linder; G,  gas  beginning 
to  escape  from  liquid. 
P  is  exactly  counter- 
poised. In  addition  to 
the  manner  described  in 
the  text,  the  experiment 
may  be  supposed  to  be 
performed  thus:  Let  the 
weight,  W,  be  deter- 
mined which,  when  the 
receiver  is  completely 
exhausted,  suffices  just  to 
keep  the  pis  'on  in  contact 
with  the  liquid.  The 
pressure  of  the  gas  is 
then  just  counter- 
balanced by  W;  and  if 
S  is  the  area  of  the  cross- 
section  of  the  piston,  the 
pressure  of  the  gas  per 

unit  of  area  is  a  .     Or,  if 

the  piston  is  hollow,  and 
mercury  is  poured  into 
it  so  as  just  to  keep  it  in  , 
contact  with  the  liquid, 
the  height  of  the  column 
of  mercury  required  is 
also  equal  to  the  pressure 
or  tension  of  the  gas. 


!48 


RESPIRATION 


exerted  directly  between  the  liquid  and  the  piston,  is  obviously  equal 
to  the  pressure  or  tension  of  the  gas  in  the  liquid. 

From  the  above  principles  it  follows  that  a  gas  held  in  solution  may 
be  extracted  by  exposure  to  an  atmosphere  in  which  the  partial  pressure 
of  the  gas  is  made  as  small  as  possible.  Thus,  oxygen  can  be  obtained 
from  liquids  in  which  it  is  simply  dissolved  by  putting  them  in  an 
atmosphere  of  hydrogen  or  nitrogen,  in  which  the  partial  pressure  of 
oxygen  is  zero,  or  in  the  vacuum  of  an  air-pump,  in  which  it  is  extremely 
small.  Heat  also  aids  the  expulsion  of  dissolved  gases.  Some  gases 
held  in  weak  chemical  union,  like  the  loosely-combined  oxygen  of 
oxyhaemoglobin,  can  be  obtained  by  dissociation  of  their  compounds 

Fig.  ii8. — Scheme  of  Gas-Pump.  A,  the  blood 
bulb;  B,  the  froth  chamber;  C,  the  drying  tube; 
D.  fixed  mercury  bulb  ;  E,  movable  mercury 
bulb  connected  by  a  flexible  tube  with  D;  F, 
eudiometer;  G,  a  narrow  delivery  tube;  i,  2,  3,  4, 
taps,  4  being  a  three-way  tap.  A  is  filled  with 
blood  by  connecting  the  tap  i  by  means  of  a 
tube  with  a  bloodvessel.  Taps  i  and  2  are  then 
closed.  The  rest  of  the  apparatus  from  B  to  D  is 
nov/  exhausted  by  raising  E,  with  tap  4  turned 
so  as  to  place  D  only  in  communication  with  G, 
till  the  mercury  fills  D.  Tap  4  is  now  turned  so  as 
to  connect  C  with  D,  and  cut  off  G  from  D,  and  E 
is  lowered.  The  mercury  passes  out  of  D,  and  air 
passes  into  it  from  B  and  C.  Tap  4  is  again  turned 
so  as  to  cut  off  C  from  D  and  connect  G  and  D.  E 
is  raised  and  the  mercury  passes  into  D  and  forces 
the  air  out  through  G,  the  end  of  which  has  not 
hitherto  been  placed  under  F.  This  alternate 
raising  and  lowering  of  E  is  continued  till  a  man- 
ometer connected  between  C  and  4  indicates  that 
the  pressure  has  been  sufficiently  reduced.  The 
tap  2  is  now  opened;  the  gases  of  the  blood  bubble  up  into  the  froth  chamber,  pass 
through  the  drying-tube  C.  which  is  filled  with  pumice-stone  and  sulphuric  acid,  and 
enter  D.  The  end  of  G  is  placed  under  the  eudiometer  F,  and  by  raising  E,  with 
tap  4  turned  so  as  to  cut  off  C,  the  gases  are  forced  out  through  G  and  collected 
in  F.  The  movements  required  for  exhaustion  can  be  repeated  several  times  till 
no  more  gas  comes  off.  The  escape  of  gas  from  the  blood  is  facilitated  by  immersing 
the  bulb  A  in  water  at  40°  to  50°  C. 

when  the  partial  piessure  is  reduced.  More  stable  combinations  may 
require  to  be  broken  up  by  chemical  agents — carbonates,  for  instance, 
by  acids. 

Extraction  of  the  Blood-Gases. — This  is  best  accomplished  by  ex- 
posing blood  to  a  nearly  perfect  vacuum.  The  gas-pumps  which  have 
been  most  largely  used  in  blood  analysis  are  constructed  on  the  principle 
of  the  Torricellian  vacuum.  A  diagram  of  a  simple  form  of  Pfliiger's 
gas-pump  is  given  in  Fig.  118,  The  gases  obtained  are  ultimately  dried 
and  collected  in  a  eudiometer,  which  is  a  graduated  glass  tube  with  its 
mouth  dipping  into  mercury.  The  carbon  dioxide  is  estimated  by 
introducing  a  little  potassium  hydroxide  to  absorb  it.  The  diminution 
in  the  volume  of  the  gas  contained  in  the  eudiometer  gives  the  volume 
of  the  carbon  dioxide.  The  oxygen  may  hz  estimated  by  putting  into 
the  eudiometer  more  than  enough  hydrogen  to  unite  with  all  the  oxygen 
so  as  to  form  water,  and  then,  after  reading  off  the  volume,  exploding 
the  mixture  by  means  of  an  electric  spark  passed  through  two  platinum 
wires  fused  into  the  glass.  One-third  of  the  diminution  of  volume 
represents  the  (Quantity  of  oxygen  present.     It  can  also  b^  cstinaated 


THE  GASES  OF  THE  BLOOD  249 

by  absorption  with  a  solution  of  pyrogallic  acid  and  potassium  hydrox- 
ide, or  an  alkahne  solution  of  sodium  hydrosulphite,  which  is  more 
cleanly.  The  remainder  of  the  original  mixture  of  blood-gases,  after 
deduction  of  the  carbon  dioxide  and  oxygen,  is  put  down  as  nitrogen 
(with,  no  doubt,  a  small  proportion  of  argon).  For  the  sake  of  easy 
comparison,  the  observed  volume  of  gas  is  always  stated  in  terms  of  its 
equivalent  at  a  standard  pressure  and  temperature  (760  mm.,  or  some- 
times on  the  Continent  i  metre  of  mercury,  and  0°  C). 

It  is  also  possible  in  various  ways  to  estimate  the  amount  of  oxygen 
in  blood  without  the  use  of  the  pump.  Thus,  since  a  definite  volume  of 
oxygen  (i'338  c.c.  at  0°  C.  and  760  mm.  pressure)  combines  with  a 
gramme  of  haemoglobin,  we  can  calculate  the  total  volume  of  oxygen 
present  if  we  know  how  much  of  the  blood-pigment  is  in  the  form  of 
oxyhajmoglobin ;  and  this  can  be  determined  by  means  of  the  spectro- 
photometer. Or  potassium  ferricyanide  may  be  added  to  the  blood. 
This  expels  the  oxygen  from  its  combination  with  the  haemoglobin, 
which  then  unites  with  an  exactly  equal  amount  of  oxygen  obtained 
from  the  ferricyanide  to  form  methaemoglobin  (Haldane)  (p.  75). 

The  Quantity  of  the  Blood-Gases. — In  arterial  and  in  venous  blood 
oxygen,  carbon  dioxide,  nitrogen,  and  argon  are  constantly  found. 
Both  the  oxj^gen  and  the  carbon  dioxide  vary  considerably  in 
amount  in  the  arterial  blood,  even  of  individuals  of  the  same  animal 
group,  and,  of  course,  much  more  in  the  venous  blood,  as  might 
naturally  be  expected,  since  even  to  the  eye  it  varies  greatly  accord- 
ing to  the  vein  it  is  obtained  from,  the  rapidity  of  the  circulation, 
and  the  activity  of  the  tissues  which  it  has  just  left.  In  one 
observation  on  blood  obtained  directly  from  a  human  artery,  21-6  c.c. 
of  oxygen,  40-3  c.c.  of  carbon  dioxide,  and  16  c.c.  of  nitrogen  were 
found  in  100  c.c.  of  blood.  The  quantity  of  oxygen  taken  up  outside 
of  the  body  by  specimens  of  human  blood  drawn  from  six  normal 
persons,  when  shaken  up  with  atmospheric  air,  varied  from  17-6  c.c. 
to  22-5  c.c.  per  100  c.c.  of  blood,  the  variations  depending  mainly 
on  the  haemoglobin  content.  The  arterial  blood  as  it  actually  left 
the  lungs  of  those  persons  must  have  contained  somewhat  less  oxygen 
(about  I  c.c.  less  per  100  c.c.  of  blood),  since  the  partial  pressure  of 
oxygen  in  the  alveolar  air  is  decidedly  below  that  in  atmospheric 
air.  In  dogs  the  amount  of  carbon  dioxide  in  arterial  blood  has 
been  found  to  vary  from  35  to  45  c.c.  per  100  c.c.  of  blood,  the 
differences  being  due  to  variations  in  the  extent  of  the  pulmonary 
ventilation  and  to  other  factors. 

In  a  series  of  observations  on  the  venous  blood  of  dogs  the  oxygen 
content  ranged  from  5-5  to i6-6  c.c.  (averageii-g  c.c),  and  the  carbon 
dioxide  content  from  38-8  c.c.  to  47-5  (average  44-3  c.c.)  per  100  c.c. 
of  blood  (Schoffer).  It  will  be  sufficiently  accurate  to  assume  that 
on  the  average,  Voiun.es  of 

0^_.  CO.,.  Na- 

100  volumes  of  arterial  blood  yield        -         -       20  40  1-2 

,,  ,,  mixed    venous    blood    (from 

right  heart)  yield 10-12      43-50        1-2 

(reduced  to  0°  C  and  760  mm-  of  uicrcury). 


250  RESPIRA  TION 

Average  venous  blood  contains  7  or  8  per  cent,  by  volume  less 
oxygen,  and  7  or  8  per  cent,  more  carbon  dioxide,  than  arterial 
blood.  Thus,  in  the  lungs  the  blood  gains  about  twice  as  many 
volumes  of  oxygen  per  cent,  as  the  air  loses,  and  the  air  gains  about 
half  as  many  volumes  of  carbon  dioxide  per  cent,  as  the  blood  loses. 
It  is  easy  to  see  that  this  must  be  so,  for  the  volume  of  air  inspired 
in  a  given  time  is  about  twice  as  great  as  that  of  the  blood  which 
passes  through  the  pulmonary  circulation  (pp.  223,  234).  Even 
arterial  blood  is  not  quite  saturated  with  oxygen;  it  can  still  take 
up  a  variable  small  amount.  The  percentage  saturation  with 
oxygen  of  the  arterial  blood  of  a  normal  woman  from  whom 
blood  was  being  transfused  into  a  patient  was  directly  determined. 
The  blood  proved  to  be  94  per  cent,  saturated — i.e.,  it  could  still 
have  taken  up  about  one-sixteenth  of  the  quantity  contained  in 
it.  Nor  is  venous  blood  nearly  saturated  with  carbon  dioxide; 
when  shaken  with  the  gas  it  can  take  up  about  150  volumes 
per  cent. 

When  the  gases  are  not  removed  from  blood  immediately  after 
it  is  drawn,  it  yields  more  carbon  dioxide  and  less  oxygen  than  if  it 
is  evacuated  at  once  (Pfluger).  From  this  it  is  concluded  that 
oxidation  goes  on  in  the  blood  for  some  time  after  it  is  shed.  The 
oxidizable  substances  are,  however,  confined  to  the  corpuscles, 
which  suggests  that  ordinary  metabolism  simply  continues  for 
some  time  in  the  formed  elements  of  the  shed  blood,  and  that  the 
disappearance  of  oxygen  is  not  due  to  the  oxidation  of  substances 
which  have  reached  the  blood  from  the  tissues. 

The  Distribution  and  Condition  of  the  Oxygen  in  the  Blood. — ^The 
oxygen  is  nearly  all  contained  in  the  corpuscles.  A  little  oxygen 
can  be  pumped  out  of  serum  (0-2  or  0-3  per  cent,  by  volume),  but  this 
follows  the  Henry-Dalton  law  of  pressures — that  is,  it  comes  off  in 
proportion  to  the  reduction  of  the  partial  pressure  of  the  oxygen  in 
the  pump,  and  is  simply  in  solution. 

When  blood  at  body  temperature  is  shaken  up  with  air  at  the 
ordinary  pressure,  corresponding  to  a  partial  pressure  of  oxygen 
of  a  little  over  one-fifth  of  an  atmosphere  (in  round  numbers  160  mm. 
of  mercury),  the  blood-pigment  becomes  saturated  with  oxygen  or 
nearly  so.  When  the  blood  is  now  pumped  out,  very  little  oxygen 
comes  off  till  the  pressure  has  been  reduced  to  about  half  an  atmo- 
sphere, corresponding  to  a  pressure  of  oxygen  of  about  80  mm. 
At  about  70  mm.  partial  pressure  the  dissociation  is  somewhat 
greater.  At  a  third  to  a  quarter  of  an  atmosphere  (50  to  40  mm.) 
the  amount  of  oxygen  liberated  is  markedly  increased,  and  the 
dissociation  becomes  more  and  more  rapid  as  the  pressure  falls 
towards  zero.  This  behaviour  shows  that  the  oxygen  is  not  simply 
absorbed,  but  is  united,  as  a  dissociable  compound,  to  some  con- 
stituent of  the  blood.     The  same  thing  is,  of   course,  seen  when 


THE  GASES  OF  THE  BLOOD 


251 


defibrinated  blood  is  saturated  at  body  temperature  with  oxygen  at 
different  pressures.  As  the  partial  pressure  of  the  gas  is  increased 
from  zero  the  first  increments  of  pressure  correspond  to  a  much 
greater  absorption  of  oxygen  than  further  equal  increments.  Thus, 
as  is  seen  in  Fig.  120,  with  an  oxygen  pressure  of  10  mm.  100  c.c. 
of  blood  took  up  6  c.c.  of  oxygen,  or  30  per  cent,  of  the  amount 
required  to  saturate  it.  When  the  pressure  of  oxygen  was  30  mm. 
over  16  c.c.  of  oxygen  was  absorbed,  the  blood  being  80  per  cent, 
saturated.     A  further  increase  of  the  oxygen  pressure  to  40  mm. 


119. — Curve  of  Dissociation  of  Oxyhaemoglobin  at  35°  C.  (after  Hiifner's  Re- 
sults). Along  the  horizontal  axis  are  plotted  the  partial  pressures  (numbers 
below  the  curve)  of  oxygen  in  air,  to  which  a  solution  of  haemoglobin  was  exposed. 
The  corresponding  percentages  of  oxygen  are  given  above  the  curve.  Along  the 
vertical  axis  is  plotted  the  percentage  saturation  of  the  haemoglobin  with  oxygen. 
Thus,  on  exposure  to  an  atmosphere  in  which  oxygen  existed  to  the  extent  of 
I  per  cent.,  corresponding  to  a  partial  pressure  of  7*6  mm.  of  mercury,  the  haemo- 
globin took  up  about  75  per  cent,  of  the  amount  of  oxygen  required  to  saturate 
it.  When  the  oxygen  was  present  in  the  atmosphere  to  the  amount  of  about  10  per 
cent.,  corresponding  to  a  partial  pressure  of  76  mm.  of  mercury,  the  quantity 
taken  up  by  the  haemoglobin  was  about  96  per  cent,  of  that  required  for  satu- 
ration. 

increased  the  quantity  of  the  gas  taken  up  by  only  2  c.c.  (to  90  per 
cent,  saturation).  The  next  increment  of  10  mm.  in  the  oxygen 
pressure  only  produced  an  additional  absorption  of  i  c.c,  and  above 
this  increasing  the  pressure  had  very  little  effect. 

We  may  suppose  that  at  the  ordinary  temperature  and  pressure 
some  oxygen  is  continually  escaping  from  the  bonds  by  which  it  is  tied 
to  the  hajmoglobin ;  but,  on  the  whole,  an  equal  number  of  free  mole- 
cules of  oxygen,  coming  within  the  range  of  the  haMnoglobin  molecules, 
are  entangled  by  them,  and  thus  equilibriuna  is  kept  up.      If  now  the 


252 


RESPIRATION 


atmospheric  pressure,  and  thexefore  the  partial  pressure  of  oxygen,  is 
reduced,  the  tendency  of  the  oxygen  to  break  off  from  the  haemoglobin 
will  be  unchanged,  and  as  many  molecules  on  the  whole  will  escape  as 
before;  but  even  after  a  considerable  reduction  of  pressure  the  haemo- 
globin, such  is  its  avidity  for  oxygen,  will  still  be  able  to  seize  as  much 
oxygen  as  it  loses.  The  more,  however,  the  partial  pressure  of  the 
oxygen  is  diminished — that  is  to  say,  the  fewer  oxygen  molecules  there 
are  in  a  given  space  above  the  haemoglobin — ^the  smaller  will  be  the 
chance  of  the  loss  being  made  up  by  accidental  captures.  At  a  certain 
pressure  the  escapes  will  become  conspicuously  more  numerous  than 
the  captures;  and  the  gas-pump  will  give  evidence  of  this.  The  higher 
the  temperature  of  the  haemoglobin  is,  the  greater  will  be  the  average 
velocity  of  the  molecules,  and  the  greater  the  chance  of  escape  of  mole- 
cules of  oxygen. 

It  is  easily  proved  that  the  substance  in  the  corpuscles  which 
unites  with  oxygen  is  the  blood-pigment.     Although  a  solution  of 

19CJC 

isac 

16CjC 
l4CiX 
I2CQ 
lOCC 

8ce. 

6CC. 
4C.C. 


100 
•0 

so 

B^ 

^ 

— 

■"" 

^""" 

-- 

^ 

K»- 

/ 

H^ 

^ 

/ 

/ 

/ 

1 

f 

/ 

•.ft 

/ 

40 

SO 
20 
IC 

1 

f 

/ 

i 

1 

L 

_. 

._ 

__ 

_ 

__ 

._ 

i. 

-    tm» 

^^    , 

__ 

,  ^ 

^  ^ 

.  ^< 

2  C.C 
0  3CC 


10     20     30     40      SO      60     70      60     90     100    HO    120    !30     140    ISO 


Fig.  120. — Curves  of  Dissociation  of  Oxygen  for  Horse's  Blood  (B)  and  Dog's  Haemo- 
globin solution  (H)  at  38°  C.  (Bohr).  The  figures  along  the  base-line  are  the 
partial  pressures  of  oxygen  to  which  the  blood  and  haemoglobin  solution  were 
exposed.  Those  along  the  vertical  axis  on  the  left  are  the  percentage  saturations 
with  oxygen.  The  figures  along  the  vertical  at  the  right  give  the  actual  number 
of  C.C.  of  oxygen  chemically  combined  by  100  c.c.  of  the  blood  for  each  pressure 
of  oxygen.  The  interrupted  line  P  indicates  the  amount  of  oxygen  dissolved  in 
the  plasma  of  the  blood  at  each  partial  pressure  on  the  assumption  that  the 
plasma  is  two-thirds  of  the  volume  of  the  blood.  Thus,  at  150  mm.  oxygen 
pressure  the  plasma  of  roo  c.c.  of  blood  took  up  o"3  c.c.  oxygen. 

oxyhsemoglobin  crystals  behaves  towards  oxygen  somewhat  differ- 
ently from  blood  containing  the  same  proportion  of  the  native  pig- 
ment, the  maximum  amount  of  oxygen  taken  up  is  the  same  for 
each.  The  differences  in  the  results  of  the  various  investigators 
who  have  worked  out  the  curves  of  dissociation  for  haemoglobin  and 
for  blood  (Figs.  119,  120,  121)  are  paitly  explained  by  the  fact  that, 
as  is  the  case  with  similar  dissociable  compounds,  the  dissociation 
tension  varies  with  the  temperature  and  the  concentration  of  the 
pigment.     Another   factor   which   was  overlooked   in  the    earher 


THE  GASES  OF  THE  BLOOD 


253 


observations  is  the  influence  of  the  carbon  dioxide  of  the  blood  on 
the  binding  power  of  hccmoglobin  for  oxygen.  It  has  been  shown 
that  the  presence  of  carbon  dioxide  increases  the  dissociation  ten- 
sion of  oxyhaemoglobin,  or,  what  is  a  different  way  of  expressing 
the  same  thing,  diminishes  the  quantity  of  oxygen  taken  up  with 
a  given  oxygen  partial  pressure  (Bohr,  Barcroft,  Fig.  121).  The 
influence  of  salts  is  also  considerable.  The  form  of  curve  obtained  by 
Hiifner  (an  equilateral  hyperbola.  Fig.  iig)  is  only  found  when  the 
haemoglobin  solution  is  thoroughly  freed  from  salts.  But  even  when 
allowance  is  made  for  all  these  factors,  the  discrepancies  seem  still 
sufficiently  definite  to  warrant  the  conclusion,  which  is  also  sup- 
ported by  other  facts,  that  the  substance  in  blood  with  which  the 
oxygen  is  loosely  united,  although,  of  course,  intimately  related  to 
the  haemoglobin  which  can  be 
artificially  prepared  from  it,  is 
yet  not  absolutely  identical  with 
the  crystalline  product.  Some 
writers  for  this  reason  prefer  to 
give  the  special  name  hsemo- 
chrome  to  the  native  blood-pig- 
ment as  it  exists  within  the 
unaltered  corpuscles,  reserving 
the  term  haemoglobin  for  the 
more  or  less  artificial  though, 
perhaps,  only  slightly  altered 
product. 

The  Distribution  and  Condition 
of  the  Carbon  Dioxide  in  the 
Blood. — The  question  is  much 
more  complicated  than  for  the 
oxygen,  which  is  practically  con- 
fined to  one  of  the  morphologi- 
cal elements  of  the  blood  (the 
erythrocytes),  and  exists  in  the  form  of  a  single  compound.  Carbon 
dioxide  is  distributed  over  the  entire  blood  in  important  amounts, 
and  is  present  is  several  forms.  The  serum  yields  a  larger  per- 
centage of  carbon  dioxide  than  the  clot,  but  this  percentage  is  not 
great  enough  to  allow  us  to  assume  that  the  whole  of  the  carbon 
dioxide  is  contained  in  the  plasma.  Somewhat  more  than  a  third 
of  it  belongs  to  the  corpuscles. 

As  regards  the  condition  of  the  carbon  dioxide,  it  is  known  that 
some  of  it  is  simply  dissolved  in  the  plasma  and  corpuscles;  but 
although  this  fraction,  on  account  of  the  relatively  high  coefficient  of 
absorption  of  the  gas  (p.  246) ,  is  much  greater  than  the  corresponding 
oxygen  fraction,  it  is  insignificant  in  comparison  with  the  quantity 
chemically   combined.      Carbon    dioxide    is    united  in    dissociable 


Fig.  121. — Dissociation  Curves  of  Blood, 
with  Difiereat  Tensions  of  CO2  (o,  3, 
20,  40,  and  90  mm.).  Ordinates  = 
percentage  saturation.  Abscissae  = 
oxygen  pressure.     (After  Barcroft.) 


254  RESPIRATION 

combinations  with  a  number  of  the  constituents  of  the  blood,  both 
inorganic  and  organic,  and  our  knowledge  of  these  combinations, 
especially  of  the  compounds  formed  with  organic  substances,  is  far 
from  complete.  The  inquiry  is  complicated  by  the  circumstance 
that  the  proportion  of  the  total  combined  carbon  dioxide  united 
with  a  given  constituent  or  bound  by  plasma  and  corpuscles  respec- 
tively is  not  constant,  but  varies  with  the  varying  tension  of  the  gas, 
while  the  total  amount  of  carbon  dioxide  is  itself  dependent  upon 
the  varying  '  titratable  alkalinity  '  (p.  25).  There  is  no  doubt  that 
some  of  the  carbon  dioxide  in  blood  is  combined  with  alkah,  but 
the  amount  of  alkali  available  is  not  nearly  sufficient  to  unite  with 
all  the  carbon  dioxide  even  in  the  form  of  bicarbonate.  Some  of 
the  dissociable  carbon  dioide  must  therefore  be  combined  with 
organic  substances.  The  relations,  even  of  that  portion  which 
exists  as  bicarbonate,  are  peculiar.  This  is  sufficiently  indicated  by 
the  fact  that  from  defibrinated  blood  the  whole  of  the  carbon 
dioxide  can  in  time  be  pumped  out  without  the  addition  of  an  acid 
to  displace  it  from  the  bases  with  which  it  is  united.  On  the  other 
hand,  from  a  bicarbonate  solution  whose  concentration  corresponds 
to  that  of  the  blood,  not  much  more  than  half  of  the  loosely  bound 
carbon  dioxide  (that  is,  the  carbon  dioxide  which  comes  off  accord- 
ing to  the  equation  2HNaC03  =  Na2C03 +CO2 +H2O)  can  be  ob- 
tained even  when  the  evacuation  is  kept  up  for  days.  This  is  only 
about  one-fourth  of  the  total  carbon  dioxide  in  the  bicarbonate; 
yet,  when  sodium  bicarbonate  is  added  to  blood,  even  in  consider- 
able amount,  all  the  carbon  dioxide  in  it  can  be  obtained  by  the 
pump.  From  serum  a  great  deal,  but  not  the  whole,  of  the  carbon 
dioxide  can  be  likewise  pumped  out,  and  the  liberation  of  the  gas 
does  not  stop,  as  in  the  case  of  the  bicarbonate  solution,  when  all 
the  bicarbonate  has  been  changed  into  carbonate.  The  residue 
(from  10  to  18  per  cent,  of  the  whole)  is  set  free  on  the  addition  of 
an  acid — e.g.,  phosphoric  acid. 

The  most  satisfactory  explanation  is  that  in  the  serum  there  exist 
substances  which  can  act  as  weak  acids  in  gradually  driving  out  the 
carbon  dioxide,  when  its  escape  is  rendered  easier  by  the  vacuum. 
The  quantity  of  these,  however,  is  not  so  large  but  that  a  portion  of 
the  carbon  dioxide  remains  in  the  serum.  The  proteins  of  the  serum, 
such  as  serum-globulin,  behave  in  certain  respects  like  weak  acids, 
and  may  contribute  to  the  driving  out  of  the  carbon  dioxide.  When 
defibrinated  blood  is  pumped  out,  the  whole  of  the  carbon  dioxide  can 
be  removed,  apparently  because  substances  of  acid  nature  pass  from 
the  corpuscles  into  the  serum  and  help  to  break  up  the  carbonates. 
The  haemoglobin  in  the  corpuscles  acts  as  a  weak  acid,  and  as  some 
corpuscles  are  haemolyzed  during  the  evacuation,  the  haemoglobin  may 
exert  this  action  in  the  serum  as  well  as  in  the  interior  of  the  corpuscles. 

The  quantity  of  carbon  dioxide  combined  with  alkah  (as  bicar- 
bonate) has  not  been  exactly  determined.  Bohr  estimated  it  by 
shaking  blood  with  atmospheric  air,  which  was  supposed  to  leave 


THE  GASES  OF  THE  BLOOD 


255 


the  bicarbonate  intact,  while  removing  nearly  all  the  rest  of  the 
carbon  dioxide,  the  compounds  of  the  gas  with  organic  constituents 
of  the  blood  being  more  easily  dissociated  than  the  bicarbonate. 
The  best  known  of  these  compounds  is  that  which  carbon  dio.xide 
seems  to  form  with  haemoglobin.  A  solution  of  haemoglobin  absorbs 
more  of  the  gas  than  water,  and  the  quantity  taken  up  is  not  pro- 
portional to  the  pressure.  There  is  also  evidence  of  the  existence 
of  dissociable  combinations  between  carbon  dioxide  and  the  proteins 
of  the  plasma,  by  which  considerable  amounts  of  the  gas  can  be 
bound  at  such  carbon  dioxide  tensions  as  normally  exist  in  blood. 

In  the  red  corpuscles  a  portion  of  the  carbon  dioxide  is  in  com- 
bination with  alkalies.  We  know  that  the  corpuscles  contain  more 
alkali  than  the  serum,  and  the  titratable  alkalinity  of  '  laked  ' 
blood  (pp.  25,  28)  is  greater  than  that  of  unlaked  blood,  unless 
a  long  time  is  allowed  in  the  case  of  the  latter  for  the  alkalies  of  the 
corpuscles  to  reach  the  acid  used  in  titration.  The  haemoglobin  of 
the  corpuscles  holds  a  portion  of  the  carbon  dioxide  in  weak  com- 
bination. 

Although  the  student  is  warned  not  to  give  too  much  weight  to 
the  actual  numbers,  the  present  position  of  our  knowledge  in  regard 
to  the  distribution  and  condition  of  the  carbon  dioxide  of  the  blood 
may  be  summed  up  by  quoting  the  calculation  of  Loewy,  that  in 
100  C.C  of  arterial  blood  containing  (with  a  carbon  dioxide  tension 
of  30  mm.  of  mercury)  40  cc  of  carbon  dioxide,  there  are — 


In  Plasma. 

In  Corpuscles. 

1 

In  Blood. 

Physically  absorbed      -         -         - 
Combined  as  bicarbonate 
In  organic  combinations 

I'2  C.C. 
I2'0      ,, 
II-8      ,, 

0'7  C.C. 
6-8    ,, 
7-5    .. 

I-g  C.C. 

i8-8    ,, 
19-3    .. 

When  blood  is  saturated  with  carbon  dioxide  and  then  separated  into 
scrum  and  clot,  the  serum  is  found  to  yield  more  gas  than  the  clot;  but 
if  the  serum  and  clot  are  separately  saturated,  the  latter  takes  up  more 
carbon  dioxide  than  the  former.  From  this  it  is  argued  that  a  substance 
combined  with  carbon  dioxide  must  in  blood  saturated  with  the  gas  pass 
out  of  the  corpuscles  into  the  serum.  Tl^e  cnrpuscles  at  the  same  time 
gain  water  and  become  larger.  The  molecular  concentration  (p.  .|2o) 
of  the  serum  of  dcfibrinated  blood,  as  measured  by  the  lowering  of  the 
freezing-point,  increases  when  it  is  saturated  with  carbon  dioxide.  On 
the  other  hand,  when  blood  is  saturated  with  oxygen,  the  corpuscles 
lose  water  and  shrink  in  volume,  while  the  molecular  concentration  of 
the  serum  is  diminished.  Hamburger  lias  extended  these  observations 
to  the  circulating  blood,  and  has  shown  that  the  plasma  of  venous 
blood  has  a  higher  percentage  of  alkali,  protein,  sugar,  and  fat  than 
the  plasma  of  arterial  blood,  and  that  the  corpuscles  have  a  greater 
volume,  though  not  a  greater  diameter.  He  therefore  supposes  that  in 
the  puhnonary  capillaries,  under  the  influence  of  oxygen,  water  passes 
into  the  plasma  from  the  corpuscles.  In  the  systemic  capillaries  the 
blood  becomes  loaded  with  carbon  dioxide,  and  therefore  the  corpuscles 


256  RESPIRA  TION 

take  up  water  from  the  plasma;  which  accordingly  has  a  more  coAcefl- 
trated  supply  of  food-substances  to  offer  to  the  tissues  than  the  plasma 
of  arterial  blood  itself.  Some  writers  see  in  this  interchange  an  auto- 
matic arrangement  by  which  oxidation  is  favoured.  Whatever  may  be 
thought  of  tlais  view — and  objections  to  it  are  not  wanting — the  current 
theory,  that  the  corpuscles  are  simply  passive  carriers  of  oxygen,  and 
exercise  no  further  influence  on  the  plasma,  breaks  down  in  face  of  the 
facts.  We  must  admit  that  an  active  and  many-sided  commerce  exists 
between  them  and  the  liquid  in  which  they  float. 

The  nitrogen  of  the  blood  is  simply  absorbed.* 

The  Tension  of  the  Blood-Gases. — If  the  gases  of  the  blood  existed 
in  simple  solution,  their  tension  or  partial  pressure  could  be  deduced 
from  the  amount  dissolved  and  the  coefficient  of  absorption.  We 
have  seen  that  they  are  mainly  combined,  and  it  is  characteristic 
of  dissociable  compounds  of  this  kind  that  the  relation  between  the 
partial  pressure  of  the  gas  in  contact  with  the  liquid  and  the  quantity 
of  gas  taken  up  is  much  more  comphcated  than  in  the  case  of  pure 
physical  absorption.  It  is  therefore  necessary  to  determine  the 
tension  directly. 

This  can  be  done  by  means  of  arrangements  called  aerotonometers. 
There  are  various  forms  of  aerotonometer,  but  the  object  of  all  is  to 
bring  the  blood  into  contact  with  an  atmosphere  or  gaseous  mixture 
into  which  the  gases  of  the  blood  can  diffuse  and  from  which  gases  can 
enter  the  blood.  When  the  composition  of  the  mixture  has  ceased  to 
change,  the  gases  in  it  are  imder  the  same  partial  pressure  as  the  corre- 
sponding gases  in  the  blood,  and  all  that  is  necessary  in  order  to  arrive 
at  the  tension  of  the  blood-gases  is  to  determine  the  final  composition 
of  the  gaseous  mixture  by  analysis.  The  speed  with  which  equilibrium 
is  attained  depends  essentially  upon  the  magnitude  of  the  surface  of 
contact  between  the  blood  and  the  gas  mixture  in  proportion  to  the 
volume  of  the  gas  space.  In  the  earlier  observations  with  the  aerotono- 
meter it  was  found  to  be  very  difhcult  to  get  complete  equilibrium,  and 
therefore  the  gas  space  was  filled  at  the  beginning  with  a  mixture  whose 
gases  had  partial  pressures  as  nearly  equal  as  possible  to  those  expected 
in  the  blood.  In  one  form  of  the  apparatus  the  blood  is  made  to  pass 
directly  from  the  vessel  to  glass  tubes,  which  it  traverses  at  the  same 
time,  the  stream  being  divided  between  them;  it  then  passes  out  again. 
The  tubes  are  warmed  by  means  of  a  water-jacket  to  the  body-tera- 
perature.  Some  of  them  are  filled  with  gaseous  mixtures  having  a 
greater,  and  the  others  with  mixtures  having  a  smaller,  partial  pressure, 
say  of 'carbon  dioxide,  than  is  expected  to  be  found  in  the  blood.  As 
the  latter  runs  in  a  thin  sheet  over  the  walls  of  the  tubes,  it  loses  carbon 
dioxide  to  some  of  them  and  takes  up  carbon  dioxide  from  others. 
From  the  alteration  in  the  proportion  of  the  carbon  dioxide  in  the  tubes, 
the  partial  pressure  of  that  gas  in  the  blood  is  calculated — that  is,  the 
partial  pressure  which  would  be  necessary  in  the  tubes  in  order  that 
the  blood  might  pass  through  them  without  losing  or  gaining  carbon 
dioxide  (p.  247). 

Bohr's  aerotonometer,  constructed  and  worked  much  in  the  same 
way  as  a  stromuhr  (p.  121),  permits  the  blood  after  passing  through  the 
gas  space  to  return  to  the  circulation.     A  stream  of  blood  can  thus  be 

*  But  according  to  Buckmaster  and  Gardner,  the  volume  of  nitrogen  in 
blood  does  not  follow  the  ordinary  physical  law.s  of  absorption  with  varying 
nitrogen  pressures  in  the  alveolar  air. 


THE  GASES  OF  THE  BLOOD 


257 


kept  in  contact  with  the  gas  for  a  quarter  of  an  hour  or  longer,  so  as 
to  insure  equilibrium.  Finally,  in  Krogh's  microlonorneler  tho  gas  space 
is  reduced  to  the  smallest  possible  dimensions,  being  composed  merely 
of  an  air-bubble  z  mm.  in  diameter,  which  is  exposed  to  the  contact  of 
a  stream  of  blood  from  an  artery  or  vein.  Equilibrium  is  established 
so  quickly  that  it  is  indifferent  whether  a  bubble  of  air  or  of  pure 
nitrogen  is  employed.  The  bubble  is  analyzed  at  the  end  of  th  ?  obser- 
vation, and  its  composition  gives  the  tension  of  the  blood  gases. 

Suppose  that  the  gaseous  mixture  which  is  in  equilibrium  with  the 
blood  contains  10  per  cent,  of  oxygen  and  5  per  cent,  of  carbon  dioxide. 

Fig.  122.  —  Krogh's  Microto- 
nometer.  The  apparatus, 
which  is  filled  with  salt  solu- 
tion, consists  of  a  graduated 
capillary  tube,  3,  the  lower 
part  of  which,  with  its  ex- 
panded lower  end,  is  shown 
on  a  much  enlarged  scale  in 
A.  The  rest  of  the  capillary 
tube,  surrounded  by  a  water- 
jacket  to  control  the  tempera- 
ture, is  shown  on  a  smaller 
scale  in  B.  2  is  a  gas-bubble, 
against  which  blood  flowing 
from  the  very  narrow  mouth 
of  the  tube  i  plays,  i  is  con- 
nected by  a  rubber  tube  with 
a  cannula  in  a  bloodvessel. 
The  blood  forces  its  way  up 
above  the  gas-bubble,  which 
is  pressed  a  little  down  by  the 
current,  and  kept  oscillating 
rapidly.  The  blood  flows  off 
through  the  tube  5,  and  is 
collected  drop  by  drop  and 
measured.  By  means  of  the 
screw  4,  shown  in  B,  which 
moves  in  mercury,  the  gas- 
bubble  can  be  drawn  into  the 
capillary  for  measurement. 
The  upper  end  of  the  capil- 
lary tube  also  expands  into  a 
funnel-shaped  cavity,  which 
is  closed  by  a  stopper,  and 
is  only  used  for  cleaning  the 
apparatus. 

the  tension  of  oxygen  in  the  blood  would  be  one-tenth  of  an  atmosphere 
[i.e.,  of  760  mm.  of  mercury),  or  76  mm  ,  and  the  tension  of  the  carbon 
dioxide  in  the  blood  one-twentieth  of  an  atmosphere,  or  38  mm.  of 
mercury. 

Another  method  by  which  the  tension  of  the  gases  in  the  venous 
blood  passing  from  tho  right  heart  through  the  lungs  has  been  estimated 
depends  upon  the  use  of  the  pulmonary  catheier.  This  consists  of  two 
tubes,  one  within  the  other.  The  inner  tube,  which  is  a  fine  elastic 
catheter,  projects  free  from  the  other  for  a  little  distance  at  its  lower 
end.  The  outer  tube  terminates  in  a  thin  india-rubbtr  balloon,  through 
which  the  inner  tube  passes  without  communicating  with  the  balloon. 

17 


258  RESPIRA  TION 

» 

The  balloon  can  be  inflated  so  as  to  block  the  bronchus  into  which  it 
is  passed,  and  cut  off  the  corresponding  portion  of  tlie  lung  from  com- 
munication with  the  outer  air.  A  sample  of  the  air  below  the  block  can 
be  drawn  off  through  the  inner  tube,  which  opens  free  in  the  bronchus. 

This  method  has  been  applied  both  to  animals  and  to  man.  In 
observations  on  man  the  catheter  was  passed  into  the  right  bronchus 
so  as  to  occlude  at  will  any  one  of  the  lobes  of  the  right  lung.  On  the 
assumption  that  the  gaseous  exchange  in  the  lungs  depends  essentially 
on  the  physical  process  of  diffusion,  the  occluded  alveoli  will  correspond 
to  the  gas  space  of  an  aerotonometer.  When  the  occlusion  has  lasted 
long  enough  for  the  gases  in  the  alveoli  and  the  blood  gases  to  come 
completely  into  equilibrium — say  half  an  hour — all  that  is  necessary  is 
to  draw  off  the  air,  and  from  its  composition  to  deduce  the  tensions  in 
the  blood.  Since  the  respiratory  function  of  the  occluded  lobe  is  in 
abeyance,  the  blood  circulating  in  it  is  all  unaltered  venous  blood,  as  it 
comes  from  the  right  ventricle,  so  that  the  gas  tensions  found  can  be 
considered  those  of  the  mixed  venous  blood. 

For  estimating  the  oxygen  tension  in  the  arterial  blood  of  man  the 
following  method  was  introduced  by  Haldane  and  Smith:  The  subject 
of  the  experiment  breathes  air  containing  a  definitely  known  very  small 
percentage  of  carbon  monoxide  until  the  haemoglobin  has  united  with 
as  much  of  that  gas  as  it  will  take  up  for  the  given  concentration  of  it 
in  the  air.  Then  the  percentage  amount  to  which  the  haemoglobin  has 
become  saturated  with  carbon  monoxide  is  determined  in  a  sample  of 
blood  taken,  say,  from  the  finger.  Now,  the  final  saturation  with 
carbon  monoxide  of  a  haemoglobin  solution  brought  into  contact  with  a 
gaseous  mixture  containing  carbon  monoxide  and  oxygen,  depends  on 
the  relative  tensions  of  the  two  gases  in  the  liquid.  But  the  tension  of 
carbon  monoxide  in  the  blood  leaving  the  lungs  will  (after  absorption 
has  ceased)  be  the  same  as  that  in  the  inspired  air.  Knowing  this 
tension  and  the  degree  of  saturation  of  the  haemoglobin  with  carbon 
monoxide,  the  oxygen  tension  in  the  blood  leaving  the  lungs — i.e.,  in 
the  arterial  blood — is  known. 

Before  proceeding  to  the  consideration  of  the  results  obtained  by 
these  diverse  methods,  it  may  be  well  to  point  out  that  when  a  gas 
is  stated  to  be  under  such  and  such  a  tension  in  the  blood,  no  direct 
information  is  given  as  to  the  quantity  of  gas  present.  For  instance, 
the  oxygen  tension  in  blood  exposed  to  atmospheric  air  will  be  the 
same  for  the  erythrocytes  as  for  the  serum — namely,  about  i6o  mm. 
of  mercury;  but  loo  cc.  of  serum  will  scarcely  contain  |  c.c.  of 
oxygen,  while  loo  c.c.  of  corpuscles  will  have  absorbed  about  60  c.c. 
of  the  gas. 

When  we  now  turn  to  the  actual  blood-gas  tensions  obtained  by 
different  observers  and  by  different  methods,  these,  as  displayed  in 
such  a  table  as  appears  on  p.  259,  seem  to  present,  at  first  sight, 
nothing  but  a  welter  of  widely  diverging  and  contradictory  figures. 

As  regards  the  venous  blood,  we  have  already  learnt  that  very 
considerable  variations  in  the  content  of  oxygen  and  of  carbon 
dioxide  are  associated  with  the  varying  functional  activity  of  the 
tissues  from  which  the  blood  comes.  This  factor,  of  course,  is  also 
not  without  influence  upon  the  gas  tensions  of  the  venous  blood. 
The  carbon  dioxide  tension  of  arterial  blood  is  affected  by  variations 


THE  GASES  OF  THE  BLOOD 


259 


in  the  amount  of  the  pulmonary  ventilation,  which  affect  the  partial 
pressure  of  the  carbon  dioxide  in  the  alveolar  air  and  thus  alter  the 
steepness  of  the  slope  of  pressure  between  the  two  sides  of  the  pul- 
monary mtmbrane. 


Arterial  Blood  : 

Venous 

Blood: 

Tension  in 

Mm.  Hg. 

Tension  in 

Mm.  Hg. 

Observer  and  Method. 

Oxygen. 

Carbon 
Dioxide. 

Oxygen. 

Carbon 
Dioxide. 

Strassburg     -         -         -         - 

21-43 

1 
16-29 

10-35 

38-49 

-4-< 

(29-6)* 

(20) 

(20-6) 

(41) 

Hertcr 

39-79 

17-31 





c  ■ 

Bolir      ----- 

101-144 

20-32 





0 

Bohr  (later  series) 

— 

9-27 



26-43 

2 

Fredericq       -         -          -         - 

91-105 

17-19 

0 

< 

Falloise          -         -         -         - 

— 

— 

17-37 

32-54 

^u 

(42-5) 

g  0  AVolffberg       -         -         -         - 

— 



(26) 

18-37 

0  o_  Nussbaum     -         -         -         - 

— 



(27) 

24-33 

^  ^    Loewy  and  Schrottcr  ~j    q 
^        Haldane  and  Smith     /  "^^^ 

(200  + 

— 

(37-7) 

34-59 
(45) 

It  is  chiefly  the  enormous  differences  in  the  recorded  oxygen 
tensions  of  the  arterial  blood  which  excite  surprise.  To  some  ex- 
tent, indeed,  these  also  may  depend  upon  differences  in  the  partial 
pressure  of  the  oxygen  in  the  alveoli,  and  it  has  been  shown  experi- 
mentally (by  the  aerotonometer)  that  with  increasing  oxygen  tension 
of  the  inspired  air  the  oxygen  tension  of  the  arterial  blood  increases 
(Fredericq).  Still,  the  differences  which  can  possibly  have  existed 
in  the  partial  pressure  of  the  oxygen  in  the  alveoh  in  the  various 
series  of  observations  can  only  to  a  small  extent  account  for  the 
differences  in  the  results.  The  main  reason  for  the  great  range  of 
values  lies  unquestionably  in  the  different  experimental  procedures 
by  which  they  were  obtained.  There  is  no  doubt  that  in  the  earlier 
observations  with  the  aerotonometer  (Strassbiu"g)  the  oxygen  of 
the  blood  could  not  have  come  into  equilibrium  with  the  mixture 
in  the  gas  space,  in  which  the  oxygen  pressure  was  at  the  beginning 
much  lower  than  that  in  the  blood;  the  results  are  therefore  too  low. 
The  same  is  true  for  the  oxygen  tension  of  the  venous  blood,  but  as 
this  is  in  any  case  considerably  smaller  than  that  of  the  arterial 
blood,  the  proportional  error  is  not  so  great.  The  later  experiments 
(of  Herter),  given  in  the  second  line  of  the  table,  yield  much  higher 
values,  owing  to  improved  technique,  but  the  findings  are  still  to  be 
regarded  as  minimal  and  not  average  results.     At  the  other  end  of 

*  The  numbers  in  brackets  are  averages. 


26o  RESPIRATION 

the  scale  stand  the  results  of  Haldane  and  Smith,  who  found  in  man 
an  oxygen  tension  in  the  arterial  blood  of  over  200  mm.  of  mercury 
equal  to  more  than  26  per  cent,  of  an  atmosphere.  This  exceeds 
the  partial  pressure  of  oxygen  in  the  external  air,  and  is  about  twice 
as  great  as  that  of  the  air  of  the  alveoli.  In  the  bird  they  found 
an  oxygen  tension  of  between  300  and  400  mm.,  equal  to  45  per 
cent,  of  an  atmosphere.  These  results,  however,  differ  so  vastly 
from  those  of  all  other  observers  that  for  the  present  it  is  best  to 
leave  them  out  of  account.  The  method  by  which  they  were  ob- 
tained, although  perhaps  correct  enough  in  principle,  seems  to  be 
exposed  to  several  sources  of  error  in  practice,  and  has  not  escaped 
criticism  as  to  its  details  (Osborne,  etc.).  We  are  left,  then,  with  a 
series  of  values  for  the  oxygen  tension  of  arterial  blood  which  lie 
always  below  the  partial  pressure  of  the  gas  in  atmospheric  air,  and 
usually  do  not  much  exceed  or  fall  much  below  100  mm.  of  mercury, 
corresponding  to  about  13  per  cent,  of  oxygen. 

The  average  tension  of  carbon  dioxide  in  the  venous  blood  passing 
through  the  lungs,  as  determined  by  the  pulmonary  catheter,  in 
man  was  45  mm.,  corresponding  to  6  per  cent,  of  an  atmosphere. 
This  agrees  fairly  well  with  most  of  the  observations  made  with  the 
aerotonometer.  The  lower  results  (of  Wolffberg  and  of  Nussbaum) 
with  the  lung  catheter  are  probably  due  to  the  fact  that  in  the  dogs 
used,  which  breathed  through  tracheal  cannulae,  the  catheter  caused 
greater  interference  with  the  respiration  than  in  man  and  induced 
dyspnoea,  with  the  consequent  washing  out  of  carbon  dioxide  (p.  246). 

The  chief  interest  of  this  discussion  of  the  blood-gas  tensions  lies 
in  their  fundamental  importance  in  the  problem  of  the  gaseous 
exchange  in  the  lungs,  on  the  one  hand,  and  between  the  blood  and 
tissues  on  the  other.    We  are  now  in  a  position  to  consider  the  former. 

Calculations  made  on  the  basis  of  such  anatomical  and  physical 
data  as  are  available  (total  surface  of  the  lungs,  thickness  of  the 
membrane  which  separates  the  air  of  the  alveoli  and  the  blood  in 
the  capillaries,  velocity  of  diffusion  of  oxygen  and  carbon  dioxide), 
indicate  that  even  with  differences  of  oxygen  tension  between  the 
blood  and  the  alveolar  air,  which  would  lie  within  the  limits  of 
error  of  our  present  methods  of  measurement,  enough  oxygen 
could  diffuse  across  the  pulmonary  membrane  to  cover  the  whole 
normal  intake.  The  speed  of  diffusion  of  carbon  dioxide  across 
such  a  membrane  being  much  greater  than  that  of  oxygen,  still 
smaller  differences  of  tension  would  suffice  to  permit  the  whole 
normal  output  of  that  gas  to  be  ehminated  b}'  diffusion.  Accord- 
ingly, the  problem  in  its  present  phase  reduces  itself  to  this,  whether, 
as  a  matter  of  fact,  the  slope  of  the  oxygen  pressure  is  always  from 
the  alveolar  air  to  the  blood  passing  through  the  lungs,  and  the 
slope  of  the  carbon  dioxide  pressure  always  from  the  blood  to  the 
alveolar  air  ? 


THE  GASES  OF  THE  BLOOD  261 

In  order  to  answer  this  question  it  is  necessary  to  know  the  partial 
pressures  of  oxygen  and  carbon  dioxide  in  the  alveoli.  The  per- 
centage of  oxygen  or  carbon  dioxide  in  expired  air  cannot  tell  us 
the  pressure  of  the  gas  in  the  alveoli,  for  the  air  in  the  upper  part 
of  the  respiratory  tract  is  necessarily  expelled  along  with  the 
alveolar  air,  and  alters  the  proportions.  But  the  mean  of  the  oxygen 
or  carbon  dioxide  percentages  in  samples  taken  from  the  last  por- 
tions of  the  air  of  two  deep  expirations,  one  following  an  ordinary 
inspiration  and  the  other  following  an  ordinary  expiration,  is  the 
mean  percentage  in  the  alveoli.  The  average  percentage  of  oxygen 
may  be  taken  as  14-5,  corresponding  to  log  mm.  of  mercury.  The 
percentage  of  carbon  dioxide  in  the  alveolar  air  while,  as  already 
remarked  (p.  239),  very  constant  in  a  given  individual,  varies  in 
different  men  from  46  to  6"2  (mean  5-5)  per  cent,  of  the  dry  alveolar 
air.  In  women  and  in  children  of  both  sexes  it  is  less  than  in  men. 
From  this  we  conclude  that  in  men  the  partial  pressure  of  carbon 
dioxide  in  the  alveoli  may  be  at  least  one-eighteenth  of  an  atmo- 
sphere, or  42  mm.  of  mercury  (Fitzgerald  and  Haldane). 

If  we  take  the  average  oxygen  tension  in  the  alveolar  air  as 
100  mm., it  is  clear  that  the  slope  of  pressure  is  very  decidedly  from  the 
alveoli  to  the  venous  blood  coming  to  the  lungs,  the  average  oxygen 
tension  in  the  observations  with  the  pulmonary  catheter  being  only 
377  mm.  It  must  be  clearly  pointed  out,  however,  that  in  the  lungs 
the  air  is  in  relation  with  arterialized  as  well  as  with  venous  blood; 
and  if  the  partial  pressure  of  oxygen  in  the  alveoli,  while  exceed- 
ing that  in  the  venous  blood',  is  inferior  to  that  in  the  arterial  blood, 
the  only  conclusion  which  could  be  drawn  would  be  that  some  of 
the  oxygen  might  pass  into  the  blood  by  diffusion,  but  that  the 
whole  of  it  could  not  do  so.  For  as  soon  as  the  oxygen  tension  in 
the  blood,  as  it  became  better  and  better  oxygenated  in  its  circuit 
through  the  lungs,  reached  the  level  of  the  alveolar  partial  pressure, 
diffusion  would,  of  course,  come  to  an  end.  According  to  the 
majority  of  observers,  however,  the  diffusion  hypothesis  surmounts 
this  test  also,  since  the  oxygen  tension  in  the  alveoli  is  invariably 
at  least  as  great  as  that  in  the  arterial  blood.  Bohr,  however, 
found  that  in  the  majority  of  his  observations  on  dogs  the  oxygen 
tension  was  distinctly  greater  in  the  arterial  blood  than  in  the  pul- 
monary air.  Even  if  we  accept  Bohr's  results,  and  they  have  been 
severely  criticized,  the  conclusion  that  the  alveolar  oxygen  tension 
far  exceeds  that  in  the  blood  of  the  right  heart  is  in  no  way  affected, 
and  this  establishes  the  possibility  of  a  large  absorption  of  oxygen 
by  the  venous  blood  in  the  lungs  through  diffusion  alone.  It  must 
be  carefully  remembered  that  even  if  it  be  admitted  that  diffusion 
can  account  for  the  absorption  of  the  whole  of  the  oxygen,  this  is 
not  of  itself  a  proof  that  it  is  by  diffusion  that  the  thing  is  actually 
done;  it  is  only  a  reason  for  refusing  to  call  in  the  aid  of   a  more 


262  RESPIRA  TION 

recondite  hypothesis,  until  the  necessity  for  doing  so  is  clearly 
demonstrated. 

It  is  unfortunate  that  complete  unanimity  has  not  been  attained 
on  this  question  in  regard  to  the  oxygen  absorption,  for  the  avail- 
able differences  of  partial  pressure  between  air  and  blood  are  much 
greater  than  in  the  case  of  the  carbon  dioxide,  and  were  it  definitely 
shown  that  the  process  is  a  physical  one  for  oxygen,  there  would  be 
little  chance  that  it  could  be  anything  else  for  carbon  dioxide.  A 
glance  at  the  table  on  p.  259  shows  that  while  the  carbon  dioxide 
tension  of  venous  blood  may  sometimes,  perhaps  generally,  exceed 
that  of  the  alveolar  air,  the  difference  is  quite  small.  The  average 
for  the  observations  on  man  with  the  pulmonary  catheter  was 
45  mm.,  which  compares  with  an  average  alveolar  tension  of  42  mm. 
If  this  excess  of  3  mm.  in  favour  of  the  blood  be  taken  to  show,  as 
it  certainly  could  be,  if  the  difference  were  a  constant  one,  that 
carbon  dioxide  can  diffuse  from  the  venous  blood,  as  it  enters  the 
pulmonary  capillaries,  into  the  air  of  the  alveoli,  the  marked  de- 
ficiency in  the  carbon  dioxide  tension  of  arterial  blood  ought  to  be 
interpreted  as  meaning  that  diffusion  is  not  the  only  way  in  which 
the  blood  gets  rid  of  its  carbon  dioxide  in  making  the  round  of  the 
pulmonary  circulation. 

In  Bohr's  experiments,  in  some  of  which  the  animals  were  made 
to  breathe  air  containing  carbon  dioxide  in  various  proportions,  the 
tension  of  that  gas  in  the  alveolar  air  was  often  greater  than  in  the 
arterial  and  even  than  in  the  venous  blood,  and  yet  carbon  dioxide 
was  given  off  by  the  blood  to  the  lungs. 

It  does  not  seem  improbable  in  itself  that  the  physical  process  of 
diffusion,  which  is  generally  considered  to  play  a  great  part,  is  aided 
by  some  other  process,  which  may  provisionally  be  termed  secre- 
tion, and  which  can  move  the  gases  even  against  the  slope  of  pres- 
sure. It  is  possible,  too,  that  when  the  conditions  are  especially 
unfavourable  to  diffusion— when,  for  instance,  the  partial  pressure 
of  carbon  dioxide  is  artificially  increased  in  the  alveoli — ^the  cells 
which  line  them  are  stimulated  to  increased  activity,  just  as  Bohr 
has  supposed  that  under  the  influence  of  the  carbon  monoxide  used 
in  the  observations  of  Haldane  and  Smith  the  absorption  of  oxygen 
was  greatly  stimulated. 

Additional  evidence  in  favour  of  the  view  that  there  is,  besides 
diffusion,  an  element  of  selective  secretion  in  the  exchange  of  gases 
through  the  pulmonary  membrane  has  been  found  by  some  writers 
in  the  results  of  a  study  of  the  gases  of  the  swim-bladder  in  fishes; 
and  to  the  extent  that  this  study  has  demonstrated  the  existence 
of  animal  cells  which  actually  secrete  gases,  it  removes  a  presump- 
tion against,  if  it  does  not  establish  a  presumption  in  favour  of,  the 
secretion  theory  of  external  respiration.  These  gases  consist  of 
oxygen,  nitrogen,  and  usually  a  small  quantity  of  carbon  dioxide, 


THE  GASES  OF  THE  BLOOD  263 

but  in  very  different  proportions  from  those  in  which  they  exist  in 
the  air  or  the  water.  Thus,  as  much  as  87  per  cent,  of  oxygen  has 
been  found  in  the  bladder  of  fishes  taken  at  a  considerable  depth, 
but  a  smaller  amount  in  those  captured  near  the  surface.  When 
the  gas  is  withdrawn  by  puncturing  the  bladder  with  a  trocar,  the 
organ  rapidly  refills,  and  the  percentage  of  oxygen  increases. 
Further,  this  process  of  gaseous  secretion  is  under  the  influence  of 
nerves,  for  gas  ceases  to  accumulate  in  the  organ  when  the  branches 
of  the  vagi  that  supply  it  are  cut.  In  the  tortoise  stimulation  of 
the  peripheral  end  of  the  vagus  causes  a  fall  of  gaseous  exchange 
in  the  corresponding  lung,  with  an  accompanying  rise  in  the  other 
lung.  That  this  is  not  the  consequence  of  an  alteration  in  the  pul- 
monary circulation  is  indicated  by  the  fact  that  the  change  is 
greater  in  the  intake  of  oxygen  than  in  the  output  of  carbon  dioxide. 
In  the  mammal,  however,  no  such  effect  has  been  clearly  demon- 
strated, and  the  decisive  proof  that  the  lungs  are  gas-secreting 
glands  which  would  be  afforded  by  the  discovery  of  secretory  nerves_ 
is  still  wanting. 

We  have  now  completed  the  description  of  the  phenomena  of 
external  respiration,  with  the  discussion  of  its  central  fact,  the 
exchange  of  gases  between  the  blood  and  the  air  at  the  surface  of 
the  lungs.  It  remains  to  trace  the  fate  of  the  absorbed  oxygen, 
and  to  determine  where  and  how  the  carbon  dioxide  arises. 


Section  V. — ^Internal  or  Tissue  Respiration. 

Seats  of  Oxidation. — The  suggestion  which  lies  nearest  at  hand, 
and  which,  as  a  matter  of  fact,  was  first  put  forward,  is  that  the 
oxygen  does  not  leave  the  blood  at  all,  but  that  it  meets  with 
oxidizable  substances  in  it,  and  unites  with  their  carbon  to  form 
carbon  dioxide.  While  there  is  a  certain  amount  of  truth  in  this 
view,  oxygen,  as  already  mentioned,  being  to  some  extent  taken  up 
by  freshly  shed  blood,  and  also  by  blood  under  other  conchtions, 
to  oxidize  bodies,  other  than  haemoglobin,  either  naturally  contained 
in  it  or  artificially  added,  there  is  no  doubt  that  the  cells  of  the  body 
are  the  busiest  seats  of  oxidation.  This  is  shown  by  the  presence 
of  carbon  dioxide  in  large  amount  in  lymph  and  other  liquids  which 
are,  or  have  been,  in  intimate  relation  with  tissue  elements;  by  its 
presence,  also  in  considerable  amount,  in  the  tissues  themselves — 
in  muscle,  for  instance;  by  its  continued  and  scarcely  lessened  pro- 
duction not  only  in  a  frog  whose  blood  has  been  replaced  by  physio- 
logical salt  solution,  and  which  continues  to  live  in  an  atmosphere 
of  pure  oxygen,  but  in  excised  muscles;  and  by  the  remarkable  con- 
nection between  the  amount  of  this  production  and  the  functional 
state  of  those  tissues.  In  insects  the  finest  twigs  of  the  tracheae, 
through  which  oxygen  passes  to  the  tissues,  actually  end  in  the  cells; 


264  RESPIRA  TION 

and  in  luminous  insects,  like  the  glow-worm,  it  has  been  noticed 
that  the  phosphorescence,  which  is  certainly  dependent  on  oxida- 
tion, begins  and  is  most  brilliant  in  those  parts  of  the  cells  of  the 
light-producing  organ  that  surround  the  ends  of  the  tracheae.  Micro- 
scopic evidence  has  been  obtained  that  the  nucleus  plays  a  predomi- 
nant part  in  intracellular  oxidation — e.g.,  in  the  indophenol  (p.  268) 
and  similar  reactions  the  coloured  oxidation  products  are  deposited 
chiefly  in  and  around  the  nuclei  of  such  cells  as  Uver  and  kidney 
cells  and  frog's  red  corpuscles  (Lillie). 

The  fact  observed  by  Bohr,  and  already  alluded  to  (p.  252),  that 
an  increase  in  the  carbon  dioxide  tension  of  blood  diminishes  its 
combining  power  for  oxygen,  and  therefore  favours  the  giving  up 
of  oxygen  to  the  lymph  and  tissues,  may  have  an  important  influence 
on  internal  respiration.  The  effect  is  much  more  marked  where  the 
oxygen  tension  is  low  than  where  it  is  high,  so  that  in  the  lungs  the 
taking  up  of  oxygen  is  scarcely  interfered  with  even  by  a  high  carbon 
dioxide  tension.  Lymph,  bile,  urine,  and  the  serous  fluids  contain 
very  little  oxygen,  but  so  much  carbon  dioxide  that  the  pressure  of 
that  gas  in  all  of  them  is  greater  than  in  arterial  blood,  while  in 
lymph  alone  (taken  from  the  large  thoracic  duct)  has  it  been  found 
less  than  that  of  venous  blood.  And  it  is  probable  that  lymph 
gathered  nearer  the  primary  seats  of  its  production  (the  spaces  of 
areolar  tissue)  would  show  a  higher  proportion  of  carbon  dioxide. 
Strassburg  found  that  with  a  pressure  of  carbon  dioxide  in  the 
arterial  blood  of  21  mm.  of  mercury,  the  pressure  in  bile  was  50  mm., 
in  peritoneal  fluid  58  mm.,  in  urine  68  mm.,  in  the  surface  of  the 
empty  intestine  58  mm.  Saliva,  pancreatic  juice,  and  milk,  also 
contain  much  carbon  dioxide,  and  only  a  little,  if  any,  oxygen. 
From  muscle  no  free  oxygen  at  all  can  be  pumped  out,  but  as  much 
as  15  volumes  per  100  of  carbon  dioxide,  some  of  which  is  free — 
that  is.  is  given  up  to  the  vacuum  alone — while  some  of  it  is  fixed, 
and  only  comes  o^  after  the  addition  of  an  acid. 

Muscle  may  be  safely  taken  as  a  type  of  the  other  tissues  in  regard 
to  the  problems  of  internal  respiration.  It  is  instructive,  therefor^, 
to  observe  that  the  great  scarcity  of  oxygen  in  the  parenchymatous 
liquidswhich  bathe  the  tissues,  here  in  the  tissues  themselves,  deepens 
into  actual  famine.  The  inference  is  plain.  The  active  tissues  are 
greedy  of  oxygen;  as  soon  as  it  enters  the  muscle  it  is  seized  and 
'  fixed  '  in  some  way  or  other.  The  traces  of  oxygen  in  the  lymph 
cannot  therefore  be  journeying  away  from  the  tissue  elements;  they 
must  have  come  from  another  source,  and  this  can  only  be  the  blood. 
Could  we  gatlicr  tissue  lymph  for  anal3^sis  directly  from  the  thin 
sheets  that  lie  between  the  blood  capillaries  and  the  tissues,  we 
might  find  more  oxygen  present  as  well  as  more  carbon  dioxide. 
But  if  we  did  find  more  oxygen,  it  would  still  be  oxygen  in  transit 
from  the  capillaries  towards  places  where  the  partial  pressure  of 


INTERNAL  OR  TISSUE  RESPIRATION  265 

oxygen  is  less.  In  the  lymph,  the  pressure  is  kept  low  by  the  avidity 
of  the  tissues  with  which  it  is  in  contact,  and  possibly  by  the  exis- 
tence in  it  of  oxidizable  substances  which  have  come  from  the  tissues. 
In  the  tissues  there  is  no  partial  pressure  at  all,  because  the  oxygen 
that  reaches  them  is  at  once  stowed  away  in  some  compound  in 
which  it  has  lost  the  properties  of  free  oxygen. 

Assuming,  then,  that  at  least  a  great  part  of  the  oxidation  and 
consequent  production  of  carbon  dioxide  goes  on  in  the  tissues,  let 
us  follow  the  steps  of  the  process,  as  far  as  we  can,  in  the  hght  of  our 
knowledge  of  the  respiration  of  muscle. 

Respiration  of  Muscle. — It  is  a  remarkable  fact  that  an  excised 
frog's  muscle  is  capable  of  going  on  yielding  carbon  dioxide  for  a 
long  time,  in  the  entire  absence  of  oxygen,  in  a  chamber,  for  instance, 
filled  with  nitrogen  or  other  indifferent  gas.     Not  only  so,  but  it 


Fig.  123. — Fatigue  of  a  Pair  of  Sartorius  Muscles  (Fletcher).  A,  in  an  atmosphere  of 
oxygen;  B,  in  an  atmosphere  of  nitrogen.  A  is  partially  restored  by  a  rest  oi 
five  minutes, 

can  be  made  to  contract  many  times  in  this  oxygen-free  atmosphere, 
although  it  loses  its  power  of  contraction  sooner  than  in  oxygen, 
and  does  not  show  the  same  capacity  for  recuperation  during  an 
interval  of  rest.  In  mammals  the  muscles  can  also  be  made  to 
contract  repeatedly  when  the  dissociable  oxygen  has.  as  far  as  pos- 
sible, been  got  rid  of  from  the  blood  by  asphyxiating  the  animal,  and 
to  give  off  a  correspondingly  large  quantity  of  carbon  dioxide, 
although  they  lose  their  contractibility  much  more  rapidly  than  the 
muscles  of  the  frog.  This  has  usually  been  interpreted  as  meaning 
that  the  carbon  dioxide  does  not  arise,  so  to  speak,  on  the  spot,  from 
the  immediate  union  of  carbon  and  o.xygen,  but  that  a  stock  of 
it  is  taken  up  by  the  muscle,  and  stored  in  some  compound  or 
compounds,  which  are  broken  down  during  contraction,  and  more 
slowly  during  rest,  carbon  dioxide  in  both  cases  being  one  of 
the  end-products.      In  a  normal  muscle  with  intact  circulation. 


266  RESPIRATION 

while  carbon  dioxide  is  given  off,  certain  of  the  other  decomposition 
products  are  supposed,  in  conjunction  with  oxygen  and  some  sub- 
stance rich  in  carbon,  Uke  sugar,  to  be  regenerated  into  the  material 
which  breaks  down  in  contraction.  When  oxygen  is  not  available, 
as  in  an  atmosphere  of  nitrogen,  carbon  dioxide  is  still  given  off,  but 
the  other  decomposition  products  are  supposed  not  to  be  regenerated 
to  contractile  substance,  but  to  accumulate  in  the  muscle,  producing 
the  phenomena  of  fatigue,  and  eventually  of  rigor. 

When  muscle  goes  into  rigor  (p.  751) — and  this  is  most  strik- 
ingly seen  when  the  rigor  is  caused  by  raising  the  temperature  of 
frog's  muscle  to  about  40°  or. 41°  C. — there  is  a  sudden  increase  in 
the  quantity  of  carbon  dioxide  given  off.  Moreover,  in  an  isolated 
muscle  the  total  quantity  of  carbon  dioxide  obtainable  during  rigor  is 
markedly  less  if  the  muscle  has  been  previously  tetanized.  From  this 
it  has  been  argued  that  the  hypothetical  substance  ("  inogen  "),  the 
decomposition  of  which  yields  carbon  dioxide  in  contraction,  is  also 
the  substance  which  decomposes  so  rapidly  in  rigor ;  that  a  given 
amount  of  it  exists  in  the  muscle  at  the  time  it  is  removed  from  the 
influence  of  the  blood;  and  that  this  can  all  explode  either  in  con- 
traction or  in  rigor,  or  partly  in  the  one  and  partly  in  the  other. 
Recent  work,  however,  has  tended  to  show  that  this  famous 
inogen  theory  has  very  little  foundation.  According  to  Fletcher, 
there  is  no  increase  in  the  amount  of  carbon  dioxide  given  off  during 
tetanus  by  an  excised  frog's  muscle  unless  the  stimulation  is  so  severe 
and  prolonged  as  to  hasten  the  onset  of  rigor.  He  therefore  supposes 
that  in  the  contraction  the  decomposition  does  not  proceed  quite  to 
the  formation  of  carbon  dioxide,  which  in  the  intact  body  is  after- 
wards liberated  from  some  more  complex  carbon-containing  waste- 
product.  He  considers  that  the  carbon  dioxide  yielded  by  excised 
muscles  is  really  preformed  carbon  dioxide,  already  existing  in  a 
state  of  loose  combination,  from  which  it  is  displaced  by  the  lactic 
acid  formed  after  excision.  There  is  no  reason  to  suppose  that  any 
independent  new  formation  of  carbon  dioxide  occurs  within  the 
isolated  muscle  in  the  absence  of  a  good  supply  of  oxygen. 

The  respiration  of  muscles  in  situ  can  be  studied  by  collecting 
samples  of  the  blood  coming  to  and  leaving  them  and  analyzing  the 
gases.  The  mere  difference  of  colour  between  the  venous  and 
arterial  blood  of  a  muscle,  or  other  active  organ,  is  sufficient  to  show 
that  oxygen  is  taken  up  and  carbon  dioxide  given  out  by  it  to  the 
blood.  This  is  the  case  in  muscles  at  rest,  and  even  in  muscles 
with  artificial  circulation  after  they  have  become  inexcitable.  In 
active  muscles  more  oxygen  is  used  up  and  more  carbon  dioxide 
produced  than  in  the  resting  state.  Chauveau  and  Kaufmann,  in 
their  experiments  on  the  levator  labii  superioris  muscle  of  the  horse  in 
feeding,  found  that  the  consumption  of  oxygen  and  the  production 
of  carbon  dioxide  might  be  many  times  as  great  in  activity  as  in  rest. 


INTERNAL  OR  TISSUE  RESPIRATION  267 

Thus  in  one  experiment  the  amount  of  oxygen  taken  in,  expressed 
in  CO.  per  gramme  of  muscle  per  minute,  was  o-oo8  during  rest,  and 
0-14  during  work;  the  corresponding  quantities  for  the  carbon 
dioxide  given  off  were  o-oo6  and  o-i8.  The  respiratory  quotient 
rose  to  1-3  in  two  experiments,  and  even  to  17  in  a  third,  showing 
that  the  increase  in  the  production  of  carbon  dioxide  was  relatively 
greater  than  the  increase  in  the  intake  of  oxygen.  These  experi- 
ments were  performed  under  conditions  so  normal  that  the  animal 
continued  to  eat  its  hay  with  seeming  unconcern  throughout  the  obser- 
vations, altliough  these  involved  the  exposure  of  the  main  blood- 
vessels of  the  muscle,  and  the  collection  of  samples  of  blood  from  them . 

For  skeletal  muscle  at  rest,  Barcroft  gives  0*004  c.c.  per  gramme 
per  minute  as  the  oxygen  consumption;  during  maximal  activity 
twenty  times  as  much  (o-o8  gramme).  In  the  heart  of  a  small  dog 
through  which  blood  was  pumped  by  a  larger  dog  the  oxygen  intake 
when  the  heart  was  beating  feebly  was,  on  the  average,  about 
o-oi  c.c.  per  gramme  of  heart-muscle  per  minute.  When  the  heart 
was  caused  to  beat  very  strongly  under  the  influence  of  adrenalin, 
the  oxygen  intake  rose  in  one  case  to  o-o8,  and  in  two  others  to  0-04. 
In  the  resting  pancreas  the  oxygen  intake  has  been  found  to  be  0-03 
to  0-05  c.c.  per  gramme  per  minute;  in  the  active  pancreas,  o-i  c.c. 
The  corresponding  number  for  the  submaxillary  gland  at  rest  is 
0-03,  and  in  activity  0-09;  for  the  kidney,  0-03  at  rest  or  during 
scanty  secretion,  and  0-07  or  even  o-og  during  active  secretion. 

Nature  of  the  Oxidative  Process. — When  we  have  recognized  the 
cells  as  the  seat  of  oxidation,  the  question  immediately  presents 
itself.  How  do  they  accomplish  the  feat  of  burning  such  masses  of 
food  substances  as  can  only  be  rapidly  oxidized  in  the  laboratory 
at  the  temperature  of  the  body  l3y  the  most  energetic  chemical 
reagents  ?  The  researches  of  late  years  have  furnished  a  key  to 
the  solution  of  this  long-standing  puzzle  by  demonstrating  the 
existence  in  the  tissues  of  oxidizing  ferments  or  oxydases.  Of  these, 
one  of  the  most  widely  distributed  is  a  ferment  which  splits  off 
oxygen  from  hydrogen  peroxide.  Since  any  oxidation  produced 
is  only  secondary  to  this  decomposition,  ferments  which  decompose 
hydrogen  peroxide  are  often  spoken  of  as  catalases,  to  distinguish 
them  from  the  o.xydascs  proper.  A  catalase  is  found  in  practically 
all  the  tissues  of  the  body,  as  well  as  in  vegetable  cells,  and  we  have 
already  mentioned  instances  of  its  action  in  connection  with  the 
oxidation  of  the  guaiaconic  acid  in  tincture  of  guaiacum  in  the 
presence  of  the  peroxide  (p.  76).  As  regards  the  activity  of  this 
ferment,  blood  comes  first;  then  follow  spleen,  liver,  pancreas, 
thymus,  brain,  muscle,  and  ovary.  It  is  present  in  the  blood-free 
organs  as  well  as  in  the  blood.  Some  tissues,  both  animal  and 
vegetable,  contain  a  ferment,  an  oxydase,  which  causes  the  oxida- 
tion of  guaiaconic  acid  in  the  presence  of  atmospheric  oxygen,  and 


268  RESPIRATION 

these  do  not  need  peroxide  of  hydrogen  in  order  to  render  guaiacum 
blue.  An  allied  ferment  which  also  induces  the  blue  colour  in 
tincture  of  guaiacum  is  the  so-called  laccase  found  in  the  most  active 
form  in  the  latex  of  the  tree  from  which  Japanese  lacquer  is  ob- 
tained, but  also  in  many  other  plants.  Many  fungi  contain  a  fer- 
ment, tyrosinase,  which  oxidizes  tyrosin,  and  in  certain  animals 
tyrosinases  have  also  been  demonstrated.  Another  well-known 
oxidizing  ferment  in  fresh  animal  tissues  is  characterized  by  the 
property  of  forming  indophenol  by  oxidation  in  an  alkaline  solution 
of  paraphenylenediamin  and  a-naphthol,  and  may  therefore  be 
termed  indophenyloxydase.  The  colourless  solution  becomes 
reddish  or  violet.  This  ferment  is  contained  in  pancreas,  salivary 
glands,  spleen,  thymus,  and  bone-marrow,  but  has  not  been  de- 
tected in  muscle,  lungs,  brain,  kidneys,  and  other  organs.  It  is 
to  be  expected  that  other  oxydases  capable  of  favouring  oxida- 
tion of  specific  kinds  of  food  substances  or  their  decomposition 
products  will  be  discovered,  but  it  ought  to  be  remarked  that 
those  at  present  known  are  only  capable  of  attacking  relatively 
simple  organic  substances,  and  it  would  be  rash  to  conclude 
that  this  is  the  only  way  in  which  living  protoplasm  can  bring 
about  the  rapid,  but  at  the  same  time  the  regulated,  oxidation 
which  is  so  characteristic  a  feature  of  its  activity.  Yet  the  capacity 
of  the  cell  to  regulate  the  intensity  and  the  extent  of  the  intra- 
cellular oxidations  would  seem  to  find  a  simple  explanation  .if  we 
assign  an  important  role  to  oxidizing  ferments  formed  by  the  cell 
itself  in  accordance  with  its  needs.  In  this  connection  we  may 
mention  a  ferment,  aldehydase,  which  was  formerly  included 
among  the  oxydases,  but  is  now  known  to  be  a  hydrolytic  enzyme. 
It  splits  aldehydes  so  as  to  yield  the  corresponding  acid — e.g., 
salicylic  aldehyde  is  split  into  sahcylic  acid  and  sahgenin.  Evidence 
of  its  presence  in  most  organs  has  been  obtained. 

Section  VI. — Relation   of   Respiration   to   the  Nervous 

System. 

The  Respiratory  Centre  and  its  Connections. — Unlike  the  beat  of 
the  heart,  the  respiratory  movements  are  entirely  dependent  on  the 
central  nervous  system.  The  '  centre  '  which  presides  over  them  is 
situated  in  the  spinal  bulb.  It  is  a  bilateral  centre — that  is,  it  has 
two  functionally  symmetrical  halves,  one  on  each  side  of  the  middle 
line.  Each  of  these  halves  has  to  do  more  particularly  with  the 
respiratory  muscles  of  its  own  side,  for  destruction  of  one-half  of 
the  spinal  bulb  causes  paralysis  of  respiration*  only  on  that  side. 
Anatomically  the  respiratory  centre  has  not  been  sharply  localized, 
but  it  lies  lower  than  the  vaso-motor  centre,  not  far  from  the  point 
of  the  calamus  scriptorius.  Stimulation  of  this  region  during  apnoea 
(p.  277)  is  stated  to  cause  co-ordinated  inspiratory  movements  and 


RELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM      269 

Widening  of  the  opening  of  the  glottis  through  abduction  of  the 
vocal  cords.  The  centre  is  brought  into  relation  with  the  muscles 
of  respiration  by  efferent  nerves.  The  phrenic  nerves  to  the  dia- 
phragm, and  the  intercostal  nerves  to  the  muscles  which  elevate 
the  ribs,  are  the  most  important  of  those  concerned  in  ordinary 
breathing.  The  respiratory  centre  is  further  related  to  afferent 
nerves,  of  which  the  most  influential  are  those  which  supply  the 
respiratory  tract  itself,  particularly  the  pulmonary  fibres  and  superior 
laryngeal  branch  of  the  vagus.  But  almost  any  afferent  nerve  may 
powerfully  affect  the  centre;  and  it  is  also  influenced  by  fibres  pass- 
ing to  it  from  the  higher  parts  of  the  central  nervous  system. 

Section  of  the  spinal  cord  in  animals  above  the  origin  of  the 
phrenic  nerves  causes  complete  paralysis  of  respiration,  and  con- 
sequent death.  The  phrenics  arise  from  the  third  and  fourth 
cervical  nerves,  and  are  joined  by  a  branch  from  the  fifth;  and  in 
man  fracture  of  any  of  the  four  upper  cervical  vertebrae  is  as  a  rule 
instantly  fatal.  But  in  one  case  respiration  was  carried  on,  and 
life  maintained  for  thirty  minutes,  merely  by  the  contraction  of  the 
muscles  of  the  neck  and  shoulders  in  a  man  entirely  paralyzed 
below  this  level  (Bell).  Section  of  the  cord  just  below  the  origin  of 
the  phrenics  leaves  the  diaphragm  working,  although  the  other 
respiratory  muscles  are  paral3'zed.  A  case  has  been  recorded  of  a 
man  in  whom,  from  disease  of  the  spine  in  the  lower  cervical  region, 
all  the  ribs  became  completely  immovable.  He  was  able  to  lead 
an  active  life,  and  to  carry  on  his  business,  although  he  breathed 
entirely  by  his  diaphragm  and  abdominal  muscles. 

Section  of  one  phrenic  is  followed  by  paralysis  of  the  correspond- 
ing half  of  the  diaphragm,  section  of  both  phrenics  by  complete 
paralysis  of  that  muscle,  and  although  respiration  still  goes  on  by 
means  of  the  muscles  which  act  upon  the  ribs,  it  is  usually  inadequate 
to  the  prolonged  maintenance  of  life.  In  the  horse,  however,  not  only 
has  survival  been  seen  after  this  operation,  but  the  animal,  after 
the  first  temporary  increase  in  the  frequency  of  the  breathing  had 
disappeared,  could  be  driven  in  a  light  vehicle  without  any  marked 
dyspnoea.  The  phrenic  nuclei  in  the  two  halves  of  the  cord  are 
connected  across  the  middle  line.  For  when  a  semisection  of  the 
cord  is  made  between  this  level  and  the  respiratory  centre  in  the 
medulla,  respiratory  impulses  are  still  able  to  reach  both  phrenic 
nerves.  In  some  animals  both  halves  of  the  diaphragm  go  on  con- 
tracting. But  when,  as  usually  happens,  this  is  not  the  case,  and 
the  diaphragm  on  the  side  of  the  semisection  has  ceased  to  act,  it 
at  once  begins  to  "infract  again  when  the  opposite  phrenic  nerve 
is  cut,  and  the  respiratory  impulse,  descending  from  the  bulb,  is 
blocked  out  from  the  direct,  and  forced  to  follow  the  crossed  path. 
It  has  been  shown  that  the  crossing  takes  place  at  the  level  of  the 
phrenic  nuclei,  and  nowhere  else  (Porter). 


270  RESPIRATION 

The  Regulation  of  the  Respiration  through  the  Afferent  Vagtls 
Fibres. — When  one  vagus  is  divided,  there  is  httle  or  no  change  in 
the  respiratory  movements.  Half  an  inch  of  one  vagus  nerve  has 
been  excised  in  removing  a  tumour,  and  the  patient  showed  no 
symptoms  whatever.  But  section  of  both  vagi  in  such  animals  as 
the  dog,  cat  and  rabbit  causes  respiration  to  become  much  deeper 
and  slower,  the  one  change  for  a  time  compensating  the  other,  so 
that  the  total  amount  of  air  taken  in  and  given  out,  the  amount  of 
carbon  dioxide  eliminated,  and  the  partial  pressure  of  that  gas  in 
the  pulmonary  alveoli  are  not  greatly  altered.  The  relative  dura- 
tion of  the  two  respiratory  phases  is  completely  changed,  inspira- 
tion being  much  more  prolonged  than  expiration.  It  has  been 
shown  that  the  effect  is  really  due  to  the  loss  of  impulses  that  nor- 
mally ascend  the  vagi,  not  to  any  irritation  of  the  cut  ends.  For  a 
nerve  can  be  frozen  without  exciting  it ;  and  when  a  portion  of  each 
vagus  is  frozen,  the  respiration  is  affected  in  precisely  the  same 
way  as  when  the  nerves  are  divided. 

After  section  of  both  vagi  certain  fibres  coming  from  the  brain 
above  the  respiratory  centre  appear  to  take  a  share  in  the  regulation 
of  the  respiratory  movements.  The  bloodvessels  supplying  these 
fibres,  or  the  centres  from  which  they  come,  can  be  blocked  by 
injection  of  paraffin  wax  into  the  common  or  internal  carotid,  or 
the  bulb  can  be  severed  with  the  knife  above  the  level  of  the  re- 
spiratory centre,  without  any  effect  being  produced  upon  the  breath- 
ing, except  that  the  rate  is  as  a  rule  somewhat  lessened.  But 
when  both  the  vagi  and  these  upper  paths  are  cut  the  character  of 
the  respiration  is  changed,  exceedingly  prolonged  inspiratory 
spasms  alternating  with  long  periods  of  complete  relaxation  of  the 
diaphragm  till  the  animal  dies. 

From  these  facts  it  appears  that  the  periodic  automatic  discharges 
of  the  respiratory  centre  are  being  continually  controlled  and  modi- 
fied by  impulses  passing  up  the  vagus,  and  that  in  the  absence  of 
these  impulses  a  certain  degree  of  control  is  exercised  by  the  higher 
paths,  which,  however,  do  not  appear  to  be  normally  in  action,  at 
any  rate  to  the  full  measure  of  their  capacity.  When  the  vagi  are 
severed,  the  control  of  the  higher  paths  comes  into  play,  and  is 
sufficient  still  to  keep  the  breathing  regular,  although  it  is  slowed. 
When  the  higher  paths  are  cut  off,  the  vagus  of  itself  is  able  to  regu- 
late the  discharge.  But  when  both  are  gone,  the  respiratory  centre, 
freed  from  nervous  control,  passes  into  a  condition  of  alternate 
spasm  and  exhaustion.  Of  the  central  connections  of  these  upper 
paths  but  little  is  surely  known.  The  corpora  quadrigemina,  how- 
ever, seem  to  contain  centres  which  can  affect  the  respiration. 
Certain  areas  on  the  cerebral  cortex  have  also  been  described,  the 
excitation  of  which  modifies  the  respiratory  movements.  There  is 
no  question  that  the  cortex  is  connected,  and  extensively  connected. 


RELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM     271 

with  the  respiratory  centre,  since  the  rate  and  depth  of  the  co- 
ordinated respiratory  movements,  which  are  universally  acknow- 
ledged to  involve  the  activity  of  the  centre,  can  be  altered  not  only 
by  the  will,  but  by  the  most  varied  psychical  events. 

The  rhythmical  excitation  of  the  regulating  vagus  fibres  must 
be  brought  about  by  either  mechanical  stimulation  of  the  nerve- 
endings  in  the  lungs,  due  to  the  alternate  stretching  and  shrinking, 
or  by  chemical  stimulation  of  these  endings  depending  on  the  changes 
that  occur  with  each  respiration  in  the  content  of  oxygen  and  carbon 
dioxide  in  the  alveolar  air,  and  therefore  in  their  pressure  (p.  260) 
in  the  blood.  Both  \news  have  found  advocates,  but  whatever 
influence  the  chemical  changes  in  the  blood  may  exert,  there  is  no 
doubt  that  the  mechanical  factors  are  the  more  important.  That 
the  vagus  is  really  excited  is  shown  by  the  fact  that  a  negative  varia- 
tion (p.  801)  is  set  up  in  the  nerve  when  the  lungs  are  inflated. 
An  electrical  change  is  also  observed  when  air  is  sucked  out  of  the 
lungs  (Alcock  and  Seemann,  Einthoven). 

When  the  normal  excitation  of  the  vagus  fibres  by  expansion  of 
the  lungs  is  exaggerated  by  closing  the  trachea  at  the  end  of  in- 
spiration, the  diaphragm  immediately  relaxes,  and  a  long  expira- 
tory pause  ensues,  broken  at  last  by  a  series  of  inspirations  much 
deeper  and  more  prolonged  than  those  which  were  taking  place 
before  occlusion.  When  the  trachea  is  occluded  at  the  end  of 
expiration,  a  series  of  deep  and  long-drawn  inspirations  occurs,  the 
first  of  which  begins  at  the  moment  when  the  next  normal  inspira- 
tion ought  to  have  taken  place  had  the  windpipe  been  left  free. 
The  most  obvious  explanation  of  these  results  is  that  the  expansion 
of  the  lungs  sets  up  impulses  in  the  vagi  which  cut  short  the  in- 
spiratory activity  of  the  respiratory  centre  (inspiration-inhibiting 
fibres),  while  in  collapse  impulses  are  set  up  which  excite  it  to  re- 
newed inspiratory  discharge  (inspiration-exciting  fibres).  Since 
ordinary  expiration  is  in  the  main  not  associated  with  active  muscular 
contraction,  the  inspiration-inhibiting  fibres  would  be  at  the  same 
time  expiration-exciting.  Clearly  this  would  constitute  a  so-called 
'  self-steering  '  arrangement,  each  inspiration  leading  inevitably  to 
the  succeeding  expiration,  and  each  expiration  providing  the  neces- 
sary stimulus  for  the  succeeding  inspiration.  On  this  hypothesis 
section  of  the  vagi  must  necessarily  be  followed  by  slowing  of  the 
respiratory  movements,  and  we  have  seen  that  this  is  the  case. 

A  rival  hypothesis  is  that  the  automatic  activity  of  the  respira- 
tory centre  leads  normally  to  the  discharge  of  motor  impulses  to 
the  inspiratory  muscles,  which  are  cut  short  at  each  expansion  of 
the  lungs  by  the  inhibitory  action  of  the  vagus,  the  nerve  not  being 
excited  during  pulmonary  collapse,  and  therefore  carrying  no  in- 
spiratory impulses  to  the  centre.  On  this  assumption,  we  may 
think  of  the  centre  as  being  '  wound  up  '  like  a  clock,  the  periodic 


272  RESPIRATION 

arrival  of  regulating  impulses  acting  like  an  escapement  movement, 
and  allowing  a  certain  amount  of  discharge.  When  the  vagi  are 
cut,  the  inspirations  are  greatly  prolonged  and  deepened,  because 
the  check  on  the  discharge  of  the  centre  has  been  removed. 

Attempts  have  been  made  by  experimental  stimulation  of  the 
vagus  trunk  to  determine  whether,  as  a  matter  of  fact,  it  contains 
both  inspiratory  and  expiratory  fibres.  But  the  results  are  neither 
so  clear  nor  so  constant  that  we  can  confidently  appeal  to  them  in 
making  a  decision,  and  even  some  of  the  investigators  who  main- 
tain the  existence  of  but  one  anatomical  set  of  fibres  believe  that 
these  are  affected  differently  by  different  kinds  of  stimulation — • 
momentary  stimuli,  for  example,  setting  up  in  them  impulses 
which  we  may  call  inspiratory,  and  long-lasting  stimuli  impulses 
which  we  may  call  expiratory. 

Excitation  of  the  central  end  of  the  cut  vagus  below  the  origin 
of  its  superior  laryngeal  branch,  with  induction  shocks  of  moderate 


fig.  124. —  Respiratory  Tracings:  Dog.  A,  normal;  B,  effect  of  stimulation  of  the 
central  end  of  vagus;  C,  effect  of  section  of  both  vagi.  (Tracing  taken  a?  in 
JPig-  135.  P-  295.)     Time-tracing,  seconds. 

strength,  certainly  causes  quickening  of  respiration.  If  the  excita- 
tion be  strong,  there  is  arrest  in  the  inspiratory  phase.  A  brief 
mechanical  stimulus,  or  a  series  of  such,  has  a  similar  effect.  But 
chemical  stimulation  {e.g.,  with  a  strong  solution  of  potassium 
chloride)  or  long-continued  mechanical  excitation  like  that  produced 
by  stretching  or  compression  of  the  nerve,  or  certain  kinds  of  elec- 
trical stimulation — for  instance,  the  very  weakest  induction  shocks, 
or  the  closure  of  an  ascending  voltaic  current* — cause  slowing  of 
the  respiratory  movements  or  expiratory  standstill.  This  is  also 
the  usual,  though  not  the  invariable  result  of  stiniiilating  the 
superior  laryngeal,  even  when  weak  induction  shocks  are  employed. 
With  stronger  stimulation  energetic  contractions  of  the  expiratory 
muscles  may  occur.  These  facts  undoubtedly  suggest  the  existence 
in  the  vagus  of  two  kinds  of  afferent  nerve-fibres  that  affect  the 
*  I  .e.,  a  current  passing  towards  the  head  in  the  nerve. 


DELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM     273 

respiratory  centre  in  opposite  ways — inspiratory  fibres,  which 
stimulate  it  to  greater  activity  of  discharge,  and  expiratory  fibres, 
which  inhibit  its  action.  The  latter  variety  we  may  suppose  to  be 
more  numerous  in  the  superior  laryngeal,  the  former  in  the  pul- 
monary branches  of  the  vagus.  And  there  is  nothing  forced  in  the 
hypothesis  that  certain  kinds  of  stimuli  act  particularly  on  the  one 
set  of  fibres,  and  certain  kinds  on  the  other,  for  we  have  already 
seen  an  instance  of  this  in  studying  the  differences  between  the  vaso- 
constrictor and  the  vaso-dilator  nerves  (p.  173). 

The  most  pmbable  conclusion,  and  the  one  which  best  reconciles  the 
conflicting  hypotheses,  is  that  two  sets  of  fibres  are  present :  (i)  Fibres 
which  inhibit  inspiration  {and  cause  expiration) ,  and  are  excited  in 
ordinary  inspiration  by  the  expansion  of  the  lungs.     (2)  Fibres  ichich 


A  a  r\ 


^"'Vv^ 


'^f-m 


„;V«V^' 


Fig.  125. — Effect  of  Stimulation  of  Central  End  of  Vagus  in  a  Cat.  Upper  Trace, 
Respiration;  Lower  Trace,  Blood-Pressure.  At  the  top  are  the  time-trace 
(seconds),  and  below  it  the  signal  line,  the  depression  in  which  indicates  the 
duration  of  the  excitation.  Practically  no  effect  was  produced  on  the  respira- 
tion, but  a  fall  of  blood-pressure  with  slowing  of  the  heart. 

cause  inspiration  {and  inhibit  expiration),  and  are  excited  in  strong 
expiration,  as  in  dyspnoea,  by  the  collapse  of  the-  lungs,  but  are  not 
active  in  ordinary  expiration. 

However  this  may  be,  the  facts  we  have  been  discussing  have  an 
importance  of  their  own,  apart  from  any  hypothetical  explanations 
of  them.  Some  of  them  have  been  more  than  once  unintentionally 
illustrated  on  man.  In  one  case  the  left  vagus  trunk  was  included 
in  a  ligature  with  the  common  carotid.  The  respiratory  move- 
ments immediately  stopped,  the  pulse  was  slowed,  and  death 
occurred  in  thirty  minutes  (Rouse).  The  superior  laryngeal  fibres, 
unlike  those  of  the  vagus  proper,  are  not  constantly  in  action,  as 
section  of  both  nerves  has  no  effect  on  respiration.  Any  source  of 
irritation  in  the  larynx  may  stinuilate  these  fibres  and  produce  a 

18 


274 


RESPIRATION 


cough,  which  may  also  be  caused  by  irritation  of  the  pulmonary 

"'iTtil'o'iVthrAff^^^^^ 

neVves  and  especially  those  of  the  face  (fifth  nerve),  abdomen  and 
chelt  have  a  marked  influence  on  respiration.  They  can  be  easily 
excited  in  the  intact  body  by  thermal  and  mechanical  stimulation. 
Icold  bath,  for  instance,  usually  causes  acceleration  and  deepemng 
of  the  respiratory  movements;  and  the  efficacy  of  mechanical  stimu- 
lation of  sensory  nerves  in  stirring  up  a  sluggish  respiratory  centre 
is  well  known  to  midwives,  who  sometimes  slap  the  buttocks  of  a  new- 


Fig  i26.-Effect  of  Stimulation  of  Central  End  of  Brachial  Nerve  o^  ff JP^^^ion 
(Upper  Tracing)  and  Blood-Pressure  (Lower  Tracing)  m  the  Cat.  At  the  top  of 
the  figure  are  the  time-trace  (seconds)  and  the  signal  line,  showmg  beginnmg  and 
end  of  stimulation. 

born  child  to  start  its  breathing.  The  reflex  expiratory  standstill 
caused  in  rabbits  by  inhalation  of  such  sharp-smelling  substances  as 
ammonia,  acetic  acid,  and  tobacco-smoke  is  due  to  afferent  impulses 
passing  up  the  trigeminus  fibres  from  the  mucous  membrane  of  the 
nose  and  is  still  obtained  after  section  of  the  olfactory  nerves. 

Another  set  of  afferent  nerves  which  have  been  supposed  by  some 
to  bear  an  important  relation  to  the  respiratory  centre  are  those 
which  supply  the  muscles.  We  have  already  noticed  that  the 
frequency  of  respiration  is  greatly  augmented  by  muscular  exercise. 
The  simplest  explanation  would  seem  to  be  that  afferent  muscular 
nerves  are  stimulated  either  by  mechanical  compression  of  their 


RELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM     275 

terminal  '  spindles,'  or  by  the  chemical  action  on  them  of  certain 
waste  products  produced  in  contraction.  It  is  quite  likely  that  this 
is  one  way  in  which  the  adjustment  is  achieved.  But  this  is  not 
the  only,  and  perhaps  not  the  most  important,  way.  For  an  in- 
crease in  the  respiratory  movements  is  caused  by  tetanizing  the 
muscles  of  a  limb  whose  nerves  have  been  completely  severed,  and 
which  is  indeed  connected  with  the  rest  of  the  body  by  no  other 
structures  than  its  bloodvessels.  This  can  only  be  due  to  two  things : 
a  direct  action  on  the  respiratory  centre  by  the  blood  that  has 
passed  through,  and  been  altered  in,  the  contracting  muscles,  or  an 
action  exerted  by  the  blood  indirectly  on  the  centre  through  the 
excitation  of  afferent  respiratory  nerves  whose  connection  with  it 
is  still  intact — for  example,  the  other  muscular  nerves  or  the  pul- 
monary branches  of  the  vagus.  That  the  action  is  direct  is  shown 
by  the  fact  that  after  section  of  the  vagi,  the  sympathetic,  and  the 
spinal  cord  below  the  origin  of.  the  phrenics,  an  increase  in  the 
respiratory  movements  is  still  produced  by  tetanizing  a  limb. 

The  Chemical  Regulation  of  the  Respiration. — However  important 
the  regulation  of  respiration  by  afferent  nervous  impulses  may  be, 
the  normal  discharge  of  the  respiratory  centre  is  intimately  associ- 
ated with  the  gases  of  the  blood. 

It  is  generally  acknowledged  that  the  centre  may  be  excited  both 
by  blood  that  is  rich  in  carbon  dioxide  and  by  blood  that  is  poor  in 
oxygen.  Stimulation  by  deficiency  of  oxygen  has  to  some  minds 
presented  a  metaphysical  difficulty — namely,  that  it  i€  not  easy  to 
see  how  the  absence  of  a  thing  could  cause  stimulation.  The  diffi- 
culty does  not  exist,  but  none  the  less  there  is  some  evidence  that 
when  oxj^gen  is  lacking  the  respiratory  centre  can  be  excited  by 
substances  like  lactic  acid,  which  are  easily  oxidizable  and  rapidly 
disappear  from  properly  oxygenated  blood.  On  the  other  hand,  it 
it  stated  that,  when  the  oxidative  processes  of  the  medullary  centres 
are  decreased  by  the  administration  of  carbon  monoxide  or  sodium 
cyanide,  the  latent  period  which  precedes  the  excitation  of  the 
respiratory  (and  other)  centres  is  so  short  that  the  stimulation 
cannot  be  attributed  to  the  accumulation  of  acid  products,  and 
that  the  mere  oxygen  want  is  of  itself  a  stimulus  for  these  centres 
(Rosenthal,  Gasser  and  Loevenhart). 

Be  that  as  it  may,  it  has  been  the  subject  of  long-continued  dis- 
cussion whether  excess  of  carbon  dioxide  or  deficiency  of  oxygen  is 
the  more  potent  stimulus  for  the  respiratory  centre.  The  best  e\-i- 
dence  points  to  the  conclusion  that  comparatively  small  alterations 
in  the  amount  of  carbon  dioxide  in  the  inspired  air  cause  a  relatively 
great  increase  in  the  respiration,  while  in  the  case  of  the  oxygen  the 
departure  from  the  normal  proportion  must  be  much  more  decided 
to  bring  about  any  notable  effect.  Nor  is  it  at  all  out  of  harmony 
with  this  that,  when  very  large  quantities  of  carbon  dioxide  (30  per 


276  RESPIRATION 

cent,  and  upwards  in  rabbits)  are  inhaled,  a  condition  of  narcosis 
comes  on  without  any  previous  respiratory  distress.  For  many 
substances  act  differently  in  large  and  in  small  doses.  Haldane  has 
pointed  out  how  exquisitely  sensitive  the  respiratory  centre  is  to  even 
small  changes  in  the  partial  pressure  of  carbon  dioxide  in  the 
alveolar  air,  and  therefore  in  the  blood  and  the  centre  itself,  and 
has  demonstrated  that  this  is  the  way  in  which  the  amount  of  the 
pulmonary  ventilation  (the  volume  of  air  breathed  per  unit  of  time) 
is  chiefly  regulated  in  ordinary  breathing. 

For  instance,  an  increase  of  as  little  as  02  per  cent,  of  carbon 
dioxide  in  the  alveolar  air,  corresponding  to  an  increase  of  14  mm. 
of  mercury  in  the  partial  pressure  (p.  246)  of  the  gas,  caused  an 
increase  in  the  pulmonary  ventilation  of  100  per  cent.  The  alveolar 
oxygen  pressure  had  to  be  diminished  to  13  per  cent,  of  an  atmo- 
sphere before  any  decided  increase  in  the  respiration  occurred. 
During  moderate  muscular  work  the  percentage  of  carbon  dioxide 
in  the  alveolar  air,  and  therefore  in  the  blood,  increases  slightly, 
causing  an  increase  in  the  ventilation,  and  this  is  one  of  the  ways  in 
which  the  hyperpnoea  associated  with  muscular  exercise  is  brought 
about.  In  severe  work  lack  of  oxygen,  with  accumulation  of  lactic 
acid  and  other  metabolic  products,  which  stimulate  the  respiratory 
centre  or  render  it  excitable  by  smaller  pressures  of  carbon  dioxide, 
also  plays  a  part. 

To  sum  up,  the  regulation  of  normal  breathing  is  twofold — a  chemical 
regulation  {through  the  carbon  dioxide)  of  the  amount  of  air  moved  into 
and  out  of  the  lungs  per  unit  of  time  ;  and  a  nervous  regulation  (chiefly 
through  the  vagi)  of  the  rate  and  depth  of  the  movements  necessary  to 
effect  the  given  amount  of  ventilation. 

When  the  vagi  have  been  divided,  an  increase  in  the  carbon 
diox'dc  pressure  within  certain  limits  is  responded  to  by  an  increase 
in  the  total  ventilation,  just  as  in  the  normal  animal,  but  the  form 
of  the  response  is  different.  Whereas  in  the  normal  animal  both 
the  rate  and  the  depth  of  respiration  are  increased,  in  the  vagoto- 
mized  animal  there  is  a  marked  increase  in  depth,  with  little  or  no 
increase  in  rate  (Scott). 

When  the  gaseous  exchange  in  the  lungs  from  any  cause  becomes 
insufficient,  the  respiratory  movements  are  exaggerated,  and  ulti- 
mately every  muscle  which  can  directly  or  indirectly  act  upon  the 
chest-wall  is  called  into  play  in  the  struggle  to  pass  more  air  into 
and  out  of  the  lungs.  To  a  lesser  and  greater  degree  of  this  exag- 
geration of  breathing  the  terms  Hyperpncea  and  Dyspncea  have  been 
respectively  applied.  If  the  gaseous  interchange  remains  insuffi- 
cient, or  is  altogether  prevented,  asphyxia  sets  in.  Sometimes  in 
man  impending  asphyxia  from  loss  of  function  by  a  part  of  the  lungs 
(with  crippling  of  the  lesser  circulation),  as  in  pneumonia,  may  be 
warded  off  by  inhalations  of  oxygen.     Increase  in  the  temperature 


J 


RELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM     277 

of  the  blood  circulating  through  the  spinal  bulb,  as  when  the  carotid 
arteries  of  a  dog  are  laid  on  metal  boxes  through  which  hot  water 
is  kept  flowing,  also  causes  dyspnoea  [heat-dyspncea)  (p.  296).  But 
if  the  temperature  be  too  high,  the  respiratory  movements  may  be 
slowed,  perhaps  by  a  partial  paralysis  or  inhibition  of  the  respiratory 
centre.  When  the  blood  is  cooled  the  respiration  becomes  deeper 
and  slower,  but  if  the  temperature  is  greatly  and  suddenly  lowered, 
the  centre  may  be  stimulated  and  the  breathing  quickened.  In 
man  the  increased  temperature  of  the  blood  in  fever  is  a  cause, 
though  not  the  only  one,  of  the  increase  in  the  rale  of  respiration. 

Apnoea.— The  physiological  opposite  of  dyspnoea  is  apncca.  This 
condition  may  be  produced  in  an  animal  by  rapid  or  prolonged 
artificial  respiration.  It  is  especially  easy  to  obtain  in  an  animal 
in  which  the  circulation  through  the  brain  and  bulb  is  interrupted 
for  a  time  and  then  restored,  while  artificial  respiration  is  being  kept 
up.  Spontaneous  respiration  returns  after  a  longer  or  shorter 
interval,  but  if  the  artificial  respiration  be  still  maintained,  it  again 
ceases.  In  a  successful  experiment  the  animal  remains  without 
breathing  for  many  seconds  after  the  artificial  respiration  is  stopped. 
In  apnoea  the  chest  remains  at  rest  in  the  expiratory  phase  if  the 
lungs  have  been  inflated  by  the  artificial  respiration  and  then  allowed 
to  collapse  of  themselves  (expiratory  apnoea),  but  in  the  inspiratory 
phase  if  they  have  been  emptied  by  suction  and  then  permitted  of 
themselves  to  expand  (inspiratory  apnoea).  The  apnoea  is  not  pro- 
duced, as  some  have  thought,  by  the  accumulation  of  an  excess  of 
oxygen  in  the  blood,  for  rapid  and  repeated  inflation  of  the  lungs 
with  hydrogen  may  cause  the  condition.  Indeed,  towards  the  end 
of  the  apnoeic  period  the  venous  blood  may  be  very  distinctly  poorer 
in  oxygen  than  normal  venous  blood.  Apnoea  is  easily  caused  in 
man  by  a  period  of  deep  and  rapid  breatliing  and  in  other  ways. 
The  essential  thing  in  this  chemical  or  true  apnoea  {apucea  vera) 
is  the  lowering  of  the  partial  pressure  of  carbon  dioxide  in  the 
alveolar  air,  and  therefore  in  the  arterial  blood  and  the  respiratory 
centre.  The  carbon  dioxide  is  washed  out  of  the  body,  so  to  say, 
by  the  excessive  pulmonary  ventilation. 

In  addition  to  chemical  apnoea,  which  is  obtainable  whether  the 
vagi  are  intact  or  not,  a  so-called  mechanical  apnoea,  or  ap)iCB.i  vagi, 
exists — that  is  to  say,  a  stoppage  of  the  respiration  due  to  an 
inhibitory  effect  produced  through  the  vagi  on  the  respiratory  centre 
when  the  vagus  endings  in  the  lungs  are  excited  mechanically  by 
inflation.  Some  observers  state  that  this  vagus  apnoea  does  not 
outlast  the  inflation.  Others  believe  that  the  results  of  successive 
inflations  can  be  '  summated  '  in  the  centre,  giving  rise  to  an  apnoea 
which  persists  after  stoppage  of  the  artificial  respiration.  That  a 
'  memory  '  of  a  prolonged  rhythmical  inflation  of  the  lungs  can 
impress  itself  in  some  way  on  the  respiratory  centre  is  shown  by 


278  RESPIRATION 

the  curious  phenomenon  that  in  resuscitation  of  the  bulb  after  a 
period  of  anaemia  the  natural  respiration,  when  it  returns,  may 
have  for  a  short  time  exactly  the  same  rhythm  as  the  artificial 
respiration  which  has  just  been  stopped. 

That  the  blood  when  the  gaseous  exchange  in  the  lungs  is  inter- 
fered with  produces  dyspnoea  by  acting  on  some  portion  of  the  brain 
may  be  shown  in  an  interesting  manner  by  establishing  what  is 
called  a  cross-circulation  in  two  rabbits  or  dogs.  The  vertebral 
arteries  and  one  carotid  are  tied  in  both  animals;  the  remaining 
carotids  are  divided  and  connected  crosswise  by  glass  tubes,  or, 
what  is  better,  as  it  avoids  the  risk  of  clotting,  they  are  crossed  by 
suturing  the  cut  ends,  so  that  the  brain  of  each  is  supplied  by  blood 
from  the  other.  When  the  respiration  is  artificially  hindered  or 
stopped  in  one  of  the  animals,  it  shows  no  dyspnoea;  it  is  in  the 
other,  whose  brain  is  being  fed  with  improperly  ventilated  blood, 
that  the  respiratory  movements  become  exaggerated.  The  point 
of  attack  of  the  '  venous  '  blood  has  been  further  locahzed  in  the 
spinal  bulb  by  the  observation  that  when  the  brain  has  been  cut 
away  above  it,  the  cord  severed  below  the  origin  of  the  phrenics, 
and  all  other  nerves  connected  with  the  region  between  the  two 
planes  of  section  divided,  any  interference  with  the  gaseous  ex- 
change in  the  lungs  is  at  once  followed  by  dyspnoea.* 

Automaticity  of  the  Respiratory  Centre. — The  question  has  been 
raised  whether,  in  the  absence  of  this  '  natural '  stimulation  by  the 
blood,  and  of  the  impulses  that  constantly  reach  the  centre  along 
its  afferent  nerves,  it  would  continue  to  discharge  itself,  or  whether 
it  would  sink  into  inaction.  We  have  already  discussed  a  similar 
question  in  regard  to  the  cardiac  and  vaso-motor  centres,  and  the 
subject  must  again  present  itself  when  we  come  to  examine  the 
functions  of  the  central  nervous  system.  In  the  meantime  it  is  only 
necessary  to  say  ^that  there  is  evidence  that  it  is  not  the  mere 
presence  of  carbon  dioxide  (or  other  substances)  in  the  blood  circu- 
lating through  the  respiratory  centre  which  determines  the  constant 
excitation  of  the  centre,  but  rather  the  accumulation  of  carbon 
dioxide  in  the  centre  itself  when  the  partial  pressure  of  that  gas  in 
the  blood  is  raised.  The  idea  that  the  continuous  excitation  of  the 
centre  is  '  autochthonous  ' — in  other  words,  that  it  is  due  to  an 
internal  stimulating  substance  or  substances  manufactured  in  the 
centre  itself,  as  well  as  carried  to  it  in  the  blood — renders  it  easy  to 
understand  that  the  discharge  of  the  respiratory  centre,  although 
modified  by  the  quality  of  the  blood  which  circulates  in  it,  is  not 
essentially  dependent  on  it.  Indeed,  in  cold-blooded  animals  whose 
blood  has  been  replaced  by  physiological  salt  solution,  and  (in  frogs) 

*  The  conclusion  is  doubtless  correct,  but  this  experiment  is  not  decisive. 
For  the  phrenic  ner\e.5  themselves  contain  afferent  fibres,  the  stimulation  of 
which  can  influence  the  respiration  after  section  of  the  vagi. 


RELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM     279 

even  after  the  circulation  has  been  stopped  altogether  by  excision 
of  the  heart,  quiet,  regular  breathing  may  be  seen  for  a  considerable 
time.  Of  course,  blood  is  essential  for  the  continued  nutrition  of  the 
centre  and  its  connections,  and  it  eventually  breaks  down  and  ceases 
to  discharge.  The  respiratory  discharge  is  still  less  dependent  for  its 
initiation  upon  the  arrival  of  afferent  impulses.  For  after  section 
of  the  bulb  above  the  centre,  of  the  cord  below  the  origin  of  the 
phrenics,  of  the  vagi  and  of  the  posterior  roots  of  all  the  upper  cer- 
vical nerves,  the  spasmodic  respiration  which  we  have  already 
described  as  occurring  when  the  vagi  and  the  higher  paths  have  been 
severed  continues  without  essential  modification.  It  has  also  been 
observed  that  during  resuscitation  of  the  bulb  and  upper  cervical 
cord  after  a  period  of  anaemia,  stimulation  of  afferent  nerves,  in- 
cluding the  vagi,  is  entirely  without  influence  on  the  respiratory 
movements  for  some  time  after  respiration  has  returned,  presumably 
because  the  sjTiapses  (p.  824)  on  the  afferent  paths  lying  within  the 
previously  anaemic  area  are  as  yet  unable  to  conduct  the  nerve 
impulses.  Nevertheless,  the  respiratory  centre  continues  steadily 
to  discharge  itself  along  the  efferent  paths,  whose  synapses  are 
situated  beyond  the  anaemic  region.  Section  of  the  bulb  above 
the  level  of  the  respiratory  centre,  and  of  the  cord  below  the  origin 
of  the  phrenic  nerves,  in  addition  to  the  anaemia,  makes  no  essential 
difference  in  the  result.  The  initial  rate  of  discharge  of  the  centre 
thus  isolated  from  afferent  impulses  is  approximately  constant  in 
different  experiments  (about  four  a  minute  in  cats). 

Spinal  Respiratory  Centres. — Although  the  chief  respiratory  centre 
lies  in  the  medulla  oblongata,  under  certain  conditions  impulses  to 
the  respiratory  muscles  may  originate  in  the  spinal  cord.  Thus,  in 
young  mammals  (kittens,  puppies),  especially  when  the  excitability 
of  the  cord  has  been  increased  by  strychnine,  in  birds  and  in  alU- 
gators,  movements,  apparently  respiratory,  have  been  seen  after 
destruction  of  the  brain  and  spinal  bulb.  In  adult  cats,  when 
the  functions  of  the  brain,  medulla,  and  cervical  cord  have  been 
abolished  by  occlusion  of  their  vessels,  similar  movements  of  the 
thoracic  and  abdominal  muscles  may  be  seen,  but  they  are  not  suffi- 
cient for  effective  respiration.  No  proof  has  ever  been  given  that 
in  the  intact  organism  the  spinal  cord  below  the  level  of  the  bulb 
takes  any  other  part  in  respiration  than  that  of  a  mere  conductor  of 
nerve  impulses;  and  it  is  not  justifiable  to  assume  the  existence  of 
automatic  spinal  respiratory  centres  on  the  strength  of  such  experi- 
ments as  these. 

Death  after  Double  Vagotomy. — Alterations  in  the  rhythm  of  respira- 
tion are  not  the  only  effects  that  follow  division  of  both  vagi  (or  vago- 
syrapathctics)  in  the  neck.  In  certain  animals,  at  least,  this  operation 
is  incompatible  with  life.  In  the  rabbit,  as  a  rule,  death  takes  place  in 
twenty-four  hours.  A  sheep  may  live  three  days,  and  a  horse  five  or 
six.     Dogs  often  live  a  week,  occasionally  a  month  or  even  two,  and  in 


28o  RESPIRA  TION 

rare  instances  they  survive  indefinitely.  The  most  prominent  syrnp- 
toms  (in  the  dog),  in  addition  to  the  marked  and  permanent  slowing 
of  respiration,  quickening  of  the  pulse  and  contraction  of  the  pupils, 
are  difficult  deglutition,  accompanied  by  frequent  vomiting  and  pro- 
gressive emaciation.  The  appetite  is  sometimes  ravenous,  but  no 
sooner  is  the  food  swallowed  than  it  is  rejected ;  and  this  is  particularly 
true  of  water  or  liquid  food.  Sometimes  the  rejected  food  is  simply 
regurgitated  after  having  reached  the  lower  end  of  the  oesophagus, 
without  entering  the  stomach.  The  fatal  result  is  usually  caused,  or 
at  least  preceded,  by  changes  of  a  pneumonic  nature  in  the  lungs.  The 
precise  significance  of  the  pulmonary  lesion  is  obscure.  But  it  would 
seem  that  paralysis  of  the  laryngeal  and  oesophageal  muscles,  with  the 
consequent  entrance  of  saliva,  food,  or  foreign  bodies,  carrying  bacteria 
into  the  lungs,  is  responsible  to  a  great  extent.  And  when  only  a  partial 
palsy  of  the  glottis  is  produced,  by  dividing  the  right  vagus  below  the 
origin  of  the  recurrent  laryngeal,  and  the  left  as  usual  in  the  neck,  pneu- 
monia either  does  not  occur  or  is  long  delayed.  It  may  be  that  the  tissue 
of  the  lungs  is  rendered  particularly  susceptible  to  such  insults  in  conse- 
quence of  trophic  or  vascular  changes  induced  by  section  of  the  pul- 
monary and  cardiac  fibres  in  the  vagi.  It  may  be  quite  clearly  demon- 
strated, however,  in  animals  which  live  for  some  weeks,  that,  not- 
withstanding the  paralysis  of  the  glottis  associated  with  aphonia,  no 
pulmonary  symptoms  may  be  present  till  a  day  or  two  before  death. 
The  picture  presented  in  these  cases  is  that  of  an  animal  suffering, 
above  all,  from  alimentary  disturbances.  The  respiration  is,  to  be  sure, 
very  different  from  the  normal  in  frequency,  depth,  and  type,  but  there 
is  nothing  to  suggest  that  the  lungs  are  the  seat  of  any  pathological 
process.  Suddenly  the  picture  changes.  Pulmonary  symptoms  ob- 
trude themselves.  The  physical  signs  of  consolidation  of  the  lungs 
may  be  detected,  and  in  a  short  time  the  animal  is  inevitably  dead. 
Occasionally  the  determining  cause  of  the  pulmonary  lesion  seems  to 
be  some  external  circumstance,  as  a  sudden  fall  of  the  air  temperature. 
The  idea  is  exceedingly  apt  to  present  itself  to  the  observer  that  the 
pneumonia  is  an  accident,  an  acute  intercurrent  affection  breaking  the 
course  of  a  chronic  malnutrition,  which  in  any  case  must  have  ended 
in  death.  Of  course,  the  vagotomized  animal  is  predisposed  to  this 
accident,  but  there  is  no  definite  time  after  section  of  the  nerves  at 
which  it  must  take  place.  The  vomiting  is  certainly  connected  with  the 
paralysis  and  consequent  dilatation  of  the  oesophagus ;  and  by  previously 
making  an  artificial  opening  into  the  stomach  or  by  a  surgical  prophy- 
laxis still  more  heroic,  the  establishment  of  a  double  gastric  and 
a3Sophageal  fistula  (p.  395),  death  may  be  prevented  for  many  months. 
Elimination  of  all  the  pulmonary  fibres  of  the  vagi,  by  extirpation  of 
one  lung,  followed  after  an  interval  by  section  of  the  opposite  vagus 
in  the  neck,  is  not  fatal  in  rabbits.  This  is  also  in  favour  of  the  view 
that  in  double  vagotomy  the  stress  falls  mainly  on  the  digestive  system. 

Innervation  of  the  Bronchial  Muscles. — Both  constrictor  and 
dilator  fibres  for  the  bronchi  are  contained  in  the  vagus.  They  are 
not  constantly  in  action,  but  can  be  reflexly  excited,  most  easily 
(in  the  dog  and  cat)  by  stimulating  the  nasal  mucous  membrane, 
and  particularly  a  small  area  well  back  upon  the  nasal  septum. 
Cauterization  of  the  corresponding  area  in  man  is  said  to  give  per- 
manent relief  in  certain  cases  of  spasmodic  asthma,  a  condition  in 
which  the  recurrent  attacks  of  dyspnoea  seem,  according  to  the  most 


RELATION  OF  RESPIRATION  TO  THE  NERVOUS  SYSTEM     281 

generally  accepted  view,  to  be  associated  with  spasm  of  the  bronchial 
muscles. 

Special  Modifications  of  the  Respiratory  Movements. — Cheyne- 
Stokes  Respiration  is  the  name  given  to  a  peculiar  type  of  breathing, 
marked  by  pauses  of  many  seconds  alternating  with  groups  of 
respirations.  In  each  group  the  movements  gradually  increase  to 
a  maximum  amplitude,  and  then  become  gradually  shallower  again, 
till  they  cease  for  the  next  pause.  The  phenomenon  often  occurs  in 
certain  diseases  of  the  brain  and  of  the  circulation,  and  pressure  on 
the  spinal  bulb  may  produce  it.  In  cats  in  which  the  circulation 
in  the  brain  and  medulla  oblongata  has  been  interrupted  for  a  time 
and  then  restored  it  is  often  noticed  at  a  certain  stage  of  resuscita- 
tion of  the  respiratory  centre.  In  frogs,  Chejme-Stokes  breathing 
has  been  observed  as  the  result  of  interference  with  the  circulation 
in  the  spinal  bulb,  '  drowning,'  or  hgature  of  the  aorta,  and  also  as 
a  consequence  of  removal  of  the  brain,  or  parts  of  it  (hemispheres 
and  optic  thalami).  But  it  is  not  peculiar  to  pathological  conditions, 
being  also  seen,  more  or  less  perfectly,  in  normal  sleep,  especially  in 
children,  in  healthy  men  at  high  altitudes,  in  hibernating  animals, 
and  in  morphine  and  chloral  poisoning. 

Well-marked  Cheyne-Stokes  breathing  can  be  obtained  experi- 
mentally in  normal  persons  in  a  variety  of  ways.  If,  for  example, 
the  subject  is  caused  to  breathe  deeply  and  frequently  for  about  two 
minutes,  so  as  to  produce  a  prolonged  apnoea,  the  respiration,  when 
it  is  resumed  spontaneously,  is  of  the  Cheyne-Stokes  type  (Haldane). 
The  explanation  given  by  Haldane  is  that  the  fall  in  the  partial 
pressure  of  the  oxygen  in  the  pulmonary  alveoli  (p.  277)  during  the 
primary  apnoea,  with  the  consequent  fall  of  oxygen  pressure  in  the 
arterial  blood  and  the  respiratory  centre,  leads  to  the  production 
of  lactic  acid  in  the  respiratory  centre  and  elsewhere,  which  stimu- 
lates the  centre  in  the  same  way  as  carbon  dioxide,  and  thus  permits 
it  to  be  excited  by  a  smaller  partial  pressure  of  carbon  dioxide  than 
that  normally  necessary.  As  soon  as  the  pressure  of  carbon  dioxide, 
which  is  increasing  dujring  the  period  of  apncea,  has  reached  the 
exciting  value  breathing  is  resumed.  The  respirations,  beginning 
as  very  feeble  movements,  rapidly  increase  in  strength  till  the 
breathing  becomes  quite  deep  or  actually  dyspnoeic.  The  store  of 
oxygen  is  replenished  by  this  thorough  ventilation  of  the  lungs,  the 
changes  in  the  excitability  of  the  respiratory  centre  due  to  lack  of 
oxygen  disappear  (perhaps  by  oxidation  of  the  lactic  acid),  and  the 
centre  relapses  into  a  period  of  repose.  During  this  period  of  apnoea 
the  oxygen  pressure  sinks  once  more  to  the  point  at  which  the  change 
in  the  excitability  of  the  respiratory  centre  by  carbon  dioxide  occurs, 
and  the  breathing  again  starts.  In  pathological  cases  the  want  of 
oxygen  may  be  associated  either  with  deficient  circulation  through 
the  bulb-centre  or  with  deficient  intake  by  the  lungs.     The  adminis- 


282  RESPIRATION 

tration  of  oxygen  through  a  mask  has  been  shown  in  such  cases  to 
aboUsh  the  periodicity  in  the  respiration,  and  to  render  it  more 
normal. 

Pecuharly  modified,  but  more  or  less  normal,  respiratory  acts  are 
coughing,  sneezing,  yawning,  sighing,  and  hiccup. 

A  cough  is  an  abrupt  expiration  with  open  mouth,  which  forces 
open  the  previously  closed  glottis.  It  may  be  excited  reflexly  from 
the  mucous  membrane  of  the  respiratory  tract  or  stomach  through 
the  afferent  fibres  of  the  vagus,  from  the  back  of  the  tongue  or 
mouth,  and  (by  cold)  from  the  skin. 

Sneezing  is  a  violent  expiration  in  which  the  air  is  chiefly  expelled 
through  the  nose.  It  is  usually  excited  reflexly  from  the  nasal 
mucous  membrane  through  the  branch  of  the  fifth  nerve  which 
supplies  it.  Pressure  on  the  course  of  the  nasal  nerve  will  often 
stop  a  sneeze.  A  bright  light  sometimes  causes  a  sneeze,  and  so  in 
some  individuals  does  pressure  on  the  supra-orbital  nerve,  when  the 
skin  over  it  is  slightly  inflamed. 

Yawning  is  a  prolonged  and  very  deep  inspiration,  sometimes 
accompanied  with  stretching  of  the  arms  and  the  whole  body.  It 
is  a  sign  of  mental  or  physical  weariness. 

A  sigh  is  a  long-drawn  inspiration,  followed  by  a  deep  expiration. 

Hiccup,  or  hiccough,  is  due  to  a  spasmodic  contraction  of  the  dia- 
phragm, which  causes  a  sudden  inspiration.  The  abrupt  closure  of 
the  glottis  cuts  this  short  and  gives  rise  to  the  characteristic  sound. 
The  following  readings  of  the  intervals  between  successive  spasms 
were  obtained  in  one  attack:  13  sees.,  12  sees.,  15  sees.,  9  sees., 
14  sees.,  etc. — i.e.,  one-fourth  or  one-fifth  of  the  frequency  of  the 
ordinary  respiratory  movements.  The  mere  fixing  of  the  attention 
on  the  observations  soon  stopped  the  hiccup. 

Hiccup  is  generally  considered  to  be  a  reflex  movement,  brought 
about  through  the  respiratory  centre  by  afferent  impulses  originating 
in  the  stomach.  The  irritation  may  be  merely  due  to  some  slight 
digestive  disturbance  set  up  by  overfilling  of  the  stomach,  perhaps. 
This  is  exceedingly  common  in  infants.  But  persistent  hiccup  may 
also  be  a  distressing  symptom  of  very  formidable  diseases — for 
example,  carcinoma  of  the  pylorus.  Experimentally,  reflex  con- 
tractions of  the  diaphragm  can  sometimes  be  elicited  by  stimulation 
of  the  central  end  of  the  vagus  at  a  time  when  no  spontaneous 
respiratory  movements  are  going  on.  This  has  been  observed,  for 
instance,  in  cats  during  resuscitation  of  the  brain  after  a  period  of 
anaemia.  In  man  also,  in  a  case  of  Cheyne- Stokes  respiration  accom- 
panied by  hiccup,  it  was  seen  that  the  hiccup  persisted  during  the 
periods  of  apnoea.  If  the  respiratory  centre  is  the  centre  for  the 
hiccup  reflex,  it  can  therefore  be  excited  by  afferent  nervous  im- 
pulses at  a  time  when  it  is  not  excited  by  the  normal  chemical 
stimulus  (MacKenzie  and  Cushny). 


INFLUENCE  OF  RESPIRATION  ON  THE  BLOOD-PRESSURE      283 

Section  VII.— The  Influenxe  of  Respiration  on  the  Blood- 
Pressure. 

We  have  already  stated,  in  treating  of  arterial  blood-pressure 
(p.  Ill),  that  a  normal  tracing  shows  a  series  of  waves  corresponding 
with  the  respiratory  movements. 

The  relationship  between  the  respiratory  phases  and  the  rise  and 
fall  of  the  blood- pressure  is  not  by  any  means  a  simple  and  invariable 
one.  It  depends  upon  a  number  of  factors,  which  need  not  be 
equally  influential  under  different  conditions  or  in  different  animals 
(Lewis).  Something  depends  upon  the  rate^  something  upon  the 
relative  preponderance  of  costal  and  abdominal  respiration,  and 
something  probably  upon  the  size  of  the  animal.  For  instance,  an 
inspiratory  rise  of  blood-pressure  occurs  in  man  with  pure  dia- 


A        ABDOMEN 


^^V,'kJUiVi 


iUwa.Jujijtj>j- 


Fig.  127. — Respiratory  Waves  in  ihe  Blood- Pressure:  Simultaneous  Tracings  of 
Movements  of  Respiration  and  of  Radial  Pulse  in  Human  Subject  (Lewis).  In 
A  the  respiration  was  diaphragmatic;  in  B,  costal.  In  A  the  respiratory  tracing 
was  taken  from  the  abdominal  wall;  in  B,  from  the  chest. 

phragmatic,  and  a  fall  with  pure  thoracic,  breathing  (Fig.  127).  In 
cats  with  fairly  fast  and  not  very  deep  respiration  the  blood-pressure 
rises  in  expiration  and  sinks  in  inspiration.  With  deep  and  slow 
respiration  the  opposite  effect  may,  upon  the  whole,  be  seen.  In 
dogs,  according  to  Einbrodt,  although  the  mean  blood-pressure  is 
falling  for  a  short  time  tit  the  beginning  of  inspiration,  it  soon  reaches 
its  minimum,  then  begins  to  rise,  and  continues  rising  during  the 
rest  of  this  period.  At  the  commencement  of  expiration  it  is  still 
mounting,  but  soon  reaches  its  maximum,  begins  to  fall,  and  con- 
tinues falling  through  the  remainder  of  the  expiratory  phase. 

A  partial  explanation  is  afforded  by  a  consideration  of  the  mechan- 
ical changes  produced  in  the  thorax  by  the  respiratory  movements. 
Of  these,  the  influence  of  variations  in  the  intrathoracic  pressure 
on  the  filling  of  the  heart  is  of  special  importance.  With  deep 
abdominal  breathing  the  changes  of  intra-abdominal  pressure  also 


284 


RESPIRATION 


affect  the  filling  of  the  heart,  an  increase  of  pressure  (in  inspiration) 
tending  to  cause  more  blood  to  be  squeezed  from  the  abdominal 
veins  towards  the  chest.  The  changes  of  vascular  resistance  in  the 
lungs,  due  to  the  alteration  in  the  cahbre  of  the  pulmonary  vessels, 
may  also  contribute,  but,  for  such  variations  of  intrathoracic 
pressure  as  normally  occur,  only  in  a  minor  degree.  The  changes 
in  the  vascular  capacity  of  the  lungs — ^that  is,  in  the  amount  of 
blood  contained  in  the  pulmonary  vessels — are  of  importance  espe- 
cially in  delaying  or  accelerating  the  alterations  of  blood-pressure  in 
the  systemic  arteries  due  to  the  other  factors. 

The  intrathoracic  pressure,  which,  as  we  have  seen,  is  always  less 
than  that  of  the  atmosphere,  unless  during  a  forced  expiration  when 
the  free  escape  of  air  from  the  lungs  is  obstructed,  diminishes  in 
inspiration  and  increases  in  expiration.  The  great  veins  outside  the 
chest,  the  jugular  veins  in  the  neck,  for  example,  are  under  the 
atmospheric  pressure,  which  is  readily  transmitted  through  their 

thin  walls,  while  the  heart  and 
thoracic  veins  are  under  a 
smaller  pressure.  The  venous 
blood  both  in  inspiration  and  ex- 
piration will,  accordingly,  tend 
to  be  drawn  into  the  right 
auricle.  In  inspiration  the  ven- 
ous flow  will  be  increased,  since 
the  pressure  in  the  thorax,  and 
therefore  in  the  pericardial 
cavity,  is  diminished ;  and  upon 
the  whole  more  venous  blood 
will  pass  into  the  right  heart 
during  inspiration  than  during  expiration.  Now,  the  right  ventricle  is 
not  in  general  working  as  hard  as  it  can  work.  Hence,  the  excess  of 
blood  which  reaches  it  during  an  inspiration  is  at  once  sent  into  the 
lungs,  although  not  even  the  first  of  it  can  have  passed  through  to 
the  left  side  of  the  heart  at  the  end  of  the  inspiration,  since  the 
pulmonary  circulation-time  (four  to  five  seconds  in  a  small  dog, 
two  to  three  seconds  in  a  rabbit)  is  longer  than  the  time  of  a  com- 
plete inspiration  at  any  ordinary  rate.  The  increase  in  the  quantity 
of  blood  pumped  into  the  pulmonary  artery  will,  if  not  counteracted 
by  other  circumstances,  tend  to  raise  the  blood- pressure  in  the 
artery  and  its  branches,  and  therefore  at  once  to  accelerate  the  out- 
flow through  the  pulmonary  veins.  This  will  be  aided  if  at  the 
same  time  the  vascular  resistance  in  the  lungs  is  reduced,  as  is 
generally  stated  to  be  the  case.  The  left  ventricle,  hke  the  right, 
is  capable  of  discharging  more  blood  than  it  ordinarily  receives.  The 
excess  of  blood  coming  to  it  is  easily  and  promptly  ejected.  The 
systemic  arteries  are  better  filled  and  the  arterial  pressure  rises. 


/ 

/ 

/l    IT 

■^i  c-V 

^      I 

r\ 

^-^          .r 

/ 

r       V 

(^    "^ 

r 

i\            ' 

Fig.  128. — The  upper  tracing  shows  the 
respiratory  movenicuts  in  a  rabbit  with 
rather  deep  and  slow  diaphragmatic 
breathing;  the  lower  tracing  is  the 
blood-pressure  curve;  /,  inspiration; 
E,  expiration,  including  the  pause. 


INFLUENCE  OF  RESPIRATION  ON  THE  BLOOD-PRESSURE     285 

In  expiration  the  contrary  will  happen.  The  return  of  blood  to 
the  thorax  will  be  checked.  This  is  well  shown  by  the  swelling  of 
the  veins  at  the  root  of  the  neck  in  expiration,  their  shrinking  in 
inspiration,  the  so-called  respiratory  venous  pulse.  Less  blood 
being  drawn  into  the  right  heart,  less  will  be  pumped  into  the  pul- 
monary artery,  in  which  the  pressure  will,  of  course,  fall.  The  out- 
flow into  the  left  auricle  will  thus  be  diminished — all  the  more  if  in 
the  expiratory  phase  the  vascular  resistance  in  the  lungs  is  increased 
— and  the  systemic  arterial  pressure  will  be  lowered.  In  both  cases, 
however,  the  change  seen  in  the  blood-pressure  curve  will  be  belated, 
and  will  not  coincide  exactly  with  the  co.nmencement  of  the  inspira- 
tion or  the  expiration.  If  it  is  delayed  for  a  period  about  equal  to 
the  length  of  an  inspiration  or  an  expiration,  the  blood-pressure 
will  be  seen  to  sink  in  inspiration  and  to  rise  in  expiration.  If 
the  period  of  delay  is  less  than  this,  the  pressure  will  be  mounting 
during  a  part  of  each  respiratory  phase  and  falling  during  the 
rest.  As  to  the  explanation  of  the  delay,  several  factors  may  be 
concerned. 

The  negative  pressure  of  the  thorax  acts  on  the  aorta,  as  well  as 
on  the  thoracic  veins,  although,  on  account  of  the  greater  thickness 
of  its  walls,  to  a  smaller  extent  than  on  the  veins.  The  diminution 
of  pressure  in  inspiration  tends  to  expand  the  thoracic  aorta,  and  to 
draw  blood  back  out  of  the  systemic  arteries,  while  expiration  has 
the  opposite  effect.  And  although  the  hindrance  caused  in  this  way 
to  the  flow  of  blood  into  the  arteries  during  inspiration,  and  the 
acceleration  of  the  flow  during  expiration  may  not  be  great,  they 
will,  of  course,  be  better  marked  in  small  animals  with  compara- 
tively yielding  arteries  than  in  large  animals.  Yet,  whether  great 
or  small,  the  tendency  will  be  to  diminish  the  pressure  in  the  one 
phase  and  increase  it  in  the  other.  As  soon  as  the  changes  of  pres- 
sure produced  by  alterations  in  the  flow  of  venous  blood  into  the 
chest  and  through  the  lungs  are  thoroughly  established,  the  arterial 
effect  will  be  overborne;  but  before  this  happens — that  is,  at  the 
beginning  of  inspiration  and  expiration — it  will  be  in  evidence,  and 
will  help  to  delay  the  main  change. 

Another  factor  in  this  delay  is  found  in  the  changes  of  vascular 
capacity  which  take  place  in  the  lungs  when  they  pass  from  the 
expanded  to  the  collapsed  condition.  The  expansion  of  the  lungs 
in  natural  respiration  causes  a  widening  of  the  pulmonary  capillaries, 
with  a  consequent  increase  of  their  capacity  and  diminution  of  their 
resistance.  When  the  vessels  at  the  base  of  the  heart  are  ligatured 
either  at  the  height  of  inspiration  or  the  end  of  expiration,  so  as 
to  obtain  the  whole  of  the  blood  in  the  lungs,  it  is  found  that  they 
invariably  contain  more  blood  in  inspiration  than  in  expiration. 
During  inspiration,  as  we  have  seen,  the  right  ventricle  is  sending 
an  increased  supply  of  blood  into  the  pulmonary  artery;  but  before 


286  RESPIRA  TION 

any  increase  in  the  outflow  through  the  pulmonary  veins  can  take 
place,  the  vessels  of  the  lung  must  be  filled  to  their  new  capacity. 
The  first  effect,  then,  of  the  lessened  vascular  resistance  of  the  lungs 
in  inspiration  is  a  temporary  falhng  off  in  the  outflow  through  the 
aorta,  and  therefore  a  fall  of  arterial  pressure.  As  soon  as  a  more 
copious  stream  begins  to  flow  through  the  lungs,  this  is  succeeded 
by  a  rise.  In  hke  manner  the  first  effect  of  expiration,  which  in- 
creases the  resistance  and  diminishes  the  capacity  of  the  pulmonary 
vessels,  is  to  force  out  of  the  lungs  into  the  left  auricle  the  blood 
for  which  there  is  no  room.  This  causes  a  rise  of  arterial  blood- 
pressure,  succeeded  by  a  fall  as  soon  as  the  lessened  blood-flow 
through  the  lungs  is  established. 

The  changes  in  the  diastolic  capacity  of  the  chambers  of  the  heart 
itself,  with  the  changes  of  pericardial  pressure,  must  also  act  in  the 


Fig.  lag. — Effect  on  Blood-Pressure  of  Inflation  of  the  Lungs:  Rabbit.  Artificial 
respiration  stopped  in  inflation  at  i.  Interval  between  2  and  3  (not  reproduced) 
51  seconds,  during  which  the  curve  was  almost  a  straight  line.  Time  tracing 
shows  seconds. 

same  direction.  It  is  obvious,  then,  how  greatly  the  rate  and  depth 
of  respiration  in  relation  to  the  size  of  the  animal  and  the  other  cir- 
cumstances already  mentioned  may  influence  the  time  relations  of 
the  respiratory  oscillations  in  the  arterial  pressure  curve,  so  that  we 
ought  not  to  expect  them  to  be  absolutely  constant. 

In  artificial  respiration  oscillations  of  blood-pressure,  synchronous 
with  the  movements  of  the  lungs,  are  also  seen.  During  inflation 
(inspiration)  the  arterial  pressure  rises;  during  deflation  (expiration)  it 
falls.  When  artificial  respiration  is  stopped  at  the  height  of  inflation 
and  the  lungs  kept  inflated  (Fig.  129),  the  arterial  blood-pressure  falls 
rapidly,  and  continues  low  until  the  rise  of  asphyxia  begins.  In  the 
fall  of  pressure  the  increased  intrathoracic  pressure  due  to  the  inflation 
is  an  important  factor.  When  the  respiration  is  stopped  in  collapse, 
instead  of  a  fall  a  steady  rise  of  pressure  occurs  (as  in  Fig.  84,  p.  186). 
This  ultimately  merges  in  the  elevation  due  to  asphyxia,  which  shows 
itself  sooner  than  in  inflation.  When  the  tracheal  cannula  is  closed  in 
natural  respiration,  no  initial  fall  of  pressure  takes  place  (Fig.  130). 


INFLUENCE  OF  RESPIRATION  ON  THE  BLOOD-PRESSURE     287 

Besides  the  mechanical  effects  of  the  respiratory  movements  on 
the  circulation,  it  may  be  influenced  by  changes  in  the  cardio- 
inhibitory  and  vaso-motor  centres  synchronous  with  the  rhythm  of 
the  respiratory  centre.  In  many  animals  (the  dog,  for  instance) 
and  in  man,  it  can  be  very  easily  made  out  that  the  rate  of  the  heart 
is  greater  during  inspiration,  especially  towards  its  end,  than  in 
expiration.  The  phenomenon  is  especially  distinct  in  deep  and 
slow  respiration.  It  is  caused  by  a  rhythmical  rise  and  fall  in  the 
activity  of  the  cardio-inhibitory  centre,  synchronous  with  the 
respiratory  movements,  for  the  difference  disappears  after  division 
of  both  vagi.  The  normal  respiratory  oscillations  of  blood-pressure 
are  not  due  in  any  great  degree  to  such  changes  in  the  rate  of  the 
heart,  for  they  persist  after  section  of  the  vagi,  and  they  are  seen  in 
animals  like  the  rabbit,  in  which  in  ordinary  breathing  little  or  no 
variation  in  the  rate  of  the  heart  is  connected  with  the  phases  of 
respiration.     The   most   probable  explanation   of  the  respiratory 


Fig.  130. — Blood-Pressure  Tracing:  Rabbit,  under  Chloral.  Natural  respiration 
stopped  at  I  in  inspiration,  at  E  in  expiration.  The  mean  blood-pressure  is 
scarcely  altered;  but  the  respiratory  waves  become  much  larger  owing  to  the 
abortive  efforts  at  breathing.     Time  tracing  shows  seconds. 

variations  in  the  pulse-rate  is  that  the  respiratory  centre,  when  it  is 
discharging  itself  in  inspiration,  sends  out  impulses  as  a  sort  of  over- 
flow along  fibres  connecting  it  with  the  cardio-inhibitory  centre. 
These  increase  the  tone  of  that  centre,  but,  owing  to  the  long  latent 
period  of  the  cardio-inhibitory  apparatus,  the  inhibition  does  not 
reveal  itself  till  the  succeeding  expiration.  It  may  be,  however,  that 
the  impulses  discharged  from  the  respiratory  centre  in  inspiration 
diminish  the  tone  of  the  cardio-inhibitory  centre,  and  thus  lead  to 
acceleration  of  the  heart  towards  the  end  of  the  inspiratory  phase. 
In  certain  pathological  conditions  the  influence  of  the  respiration  on 
the  pulse-rate  is  exaggerated  (so-called  '  respiratory  arhythmia  '). 

Traube-Hering  Curves. — Rhythmical  changes  in  the  activity  of 
the  vaso-motor  centre,  also  associated  with  periodic  discharges  from 
the  respiratory  centre,  may  be  observed  under  certain  conditions — 
e.g.,  when  in  an  animal  paralyzed  by  curara,  and  therefore  unable  to 
breathe  spontaneously,  the  artificial  respiration  is  stopped  for  a  time. 


/^/ 


288  RESPIRA  TION 

If  such  a  dose  of  curara  be  given  as  will  still  permit  slight  spontaneous 
respiration  to  go  on,  and  both  vagi  be  cut,  it  can  be  seen  on  stopping 
the  artificial  respiration  that  the  waves  on  the  blood-pressure  curve 
are  exactly  sjmchronous  with  the  slow  respiratory  movements.  The 
Traube-Hering  waves  sink  in  inspiration  and  rise  in  expiration. 

The  fact  that  they  have  invariably  a  longer  period  than  the 
natural  respiratory  movements  indicates  that  they  are  not  concerned 
in  the  production  of  the  normal  respiratory  oscillations  of  arterial 
pressure.  Probably  the  reason  why  the  Traube  waves  appear  after 
section  of  the  vagi  is  the  increased  vigour  of  the  slow  respiratory 
discharges,  coupled  with  a  hyperexcitability  of  the  vaso-motor 
centre,  due  to  the  long  pauses  in  the  aeration  of  the  blood.  In  the 
asphyxial  rise  of  pressure  in  a  curarized  dog  they  are  constantly 
seen,  and  are  often  observed  when  the  circulation  in  the  medulla 


«*^^#%,«,^,       p 
^%««« 


Fig.  131. — Traube-Hering  Waves  as  the  Blood-Pressure  is  falling  during  Occlusion 
of  the  Cerebral  Arteries  in  a  Cat. 

oblongata  is  in  any  way  interfered  with  (Fig.  131)-  In  addition  to 
the  true  Traube-Hering  waves,  other  and  much  longer  periodic 
variations  in  the  blood-pressure  are  sometimes  noticed.  If  spon- 
taneous respiration  is  going  on,  their  long  sweeping  curves  then  show 
the  ordinary  respiratory  waves  superposed  on  them. 

The  normal  respiratory  oscillations  in  the  veins,  as  might  be 
expected,  run  precisely  in  the  opposite  direction  to  those  in  the 
arteries,  and  so  do  the  Traube-Hering  curves.  The  increased  flow 
from  the  veins  to  the  thorax  during  inspiration  lowers  the  pressure 
in  the  jugular  vein,  while  it  increases  the  pressure  in  the  carotid. 
The  constriction  of  the  small  bloodvessels  to  which  the  Traube- 
Hering  curves  are  due  increases  the  blood-pressure  in  the  arteries, 
because  it  increases  the  peripheral  resistance  to  the  blood- flow;  in 
the  veins  it  lowers  the  pressure,  because  less  blood  gets  through  to 
them.  Accordingly,  when  the  Traube-Hering  curve  is  ascending  in 
the  carotid,  it  is  descending  in  the  jugular. 


EFFECTS  OF  BREATHING  CONDENSED  AND  RAREFIED  AIR     289 

The  respiratory  variations  in  the  volume  of  the  brain,  which  are 
so  striking  a  phenomenon  when  a  trephine  hole  is  made  in  the 
skull,  but  which  can  also  take  place,  thanks  to  the  displacement  of 
cerebro-spinal  fluid  (p.  174),  when  the  cranium  is  intact,  have  by 
some  been  attributed  to  interference  with  the  venous  outflow  from 
the  cranial  cavity  during  expiration,  and  by  others  to  those  changes 
in  the  arterial  pressure  whose  causes  we  have  just  been  discussing. 
The  truth  is  that  neither  factor  is  exclusively  concerned.  The  ques- 
tion turns  largely  upon  the  time-relations  of  the  movements.  The 
swelling  of  the  brain  is  sometimes  synclironous  with  expiration,  and 
the  shrinking  with  inspiration.  Here  the  damming  back  of  the 
blood  in  the  sinuses  when  the  outflow  is  checked  by  the  expiratory 
rise  of  pressure  in  the  thoracic  veins  either  conspires  with  an  expira- 
tory rise  of  arterial  pressure  or  is  more  than  enough  to  counter- 
balance an  expiratory  fall  of  pressure  in  the  cerebral  arteries  if  the 
respiratory  conditions  are  such  as  to  lead  to  an  expiratory  fall.  But 
sometimes  the  dura  mater  bulges  into  the  trephine  hole  in  inspira- 
tion and  sinks  down  in  expiration.  Here  the  increase  in  the  volume 
of  the  brain  produced  by  the  increased  pressure  in  the  arteries  and 
capillaries  in  inspiration  is  more  than  sufficient  to  counterbalance 
the  quickened  escape  of  blood  from  the  cerebral  veins. 

Section  VHI. — ^The   Effects   of   breathing   Condensed   and 

Rarefied  Air. 

These  are — -(i)  mechanical,  shown  chiefly  by  changes  in  the  cir- 
culation, in  the  blood-pressure,  for  instance ;  (2)  chemical. 

The  mechanical  effects  differ  according  to  whether  the  whole  body, 
or  only  the  respiratory  tract,  is  exposed  to  the  altered  pressure. 
When  the  trachea  of  an  animal  is  connected  with  a  chamber  in 
which  the  pressure  can  be  raised  or  lowered,  it  is  found  that  at  first 
the  arterial  blood-pressure  rises  as  the  pressure  of  the  air  of  respira- 
tion is  increased  above  that  of  the  atmosphere.  But  a  maximum 
is  soon  reached;  and  when  respiration  begins  to  be  impeded,  the 
pressure  falls  in  the  arteries  and  increases  in  the  veins.  When  the 
pressure  of  the  air  in  the  chamber  is  diminished  a  little  below  that 
of  the  atmosphere,  there  is  a  slight  sinking  of  the  arterial  blood- 
pressure,  which  rises  if  the  air-pressure  is  further  diminished. 

It  is  clear  that  any  change  of  the  air-pressure  which  tends  to  diminish 
the  intrathoracic  pressure  will  favour  the  venous  return  to  the  heart, 
and  therefore,  if  the  exit  of  blood  from  the  thorax  is  not  proportionally 
impeded,  tlie  filling  of  the  arteries.  An  increase  in  the  intra-alvcolar 
pressure  must  tend  on  the  whole  to  increase,  and  a  diminution  in  it  to 
lessen,  the  pressure  inside  the  thorax,  which  always  remains  ecjual  to 
the  intra-alvcolar  pressure,  minus  the  elastic  tension  of  the  lungs. 
Breathing  compressed  air  should,  therefore,  under  the  conditions 
described,  be  upon  the  whole  unfavourable  to  the  venous  return  to  the 

19 


ago 


RESPIRATION 


heart  and  to  the  filling  of  the  arteries,  and  the  arterial  pressure  should 
fall;  while  breathing  rarefied  air  should  have  the  opposite  effect.  But 
a  very  great  diminution  of  the  intrathoracic  pressure  is  not  necessarily- 
favourable  to  the  circulation,  since  the  auricles  are  then  unable  to  con- 
tract perfectly. 

Certain  chest  diseases  have  been  treated  by  the  use  of  apparatus  by 
which  the  patient  is  made  to  breathe  either  compressed  or  rarefied  air ; 
or  to  inspire  air  at  one  pressure  and  to  expire  into  air  at  another  pressure. 
And  it  has,  upon  the  v/hole,  been  found,  in  agreement  with  theory, 
that  condensed  air  cannot  help  the  circulation  however  it  is  applied,  but 
always  hinders  it ;  wliile  rarefied  air  aids  the  circulation  both  in  inspira- 
tion and  in  expiration.  But 
the  increased  work  of  the  in- 
spiratory muscles  may  coun- 
terbalance the  advantage. 

V alsalvas  experiment, 
which  is  performed  by  closing 
the  mouth  and  nostrils  after 
a  previous  inspiration,  and 
then  forcibly  trying  to  expire, 
is  an  imitation  of  breathing 
into  compressed  air.  The 
intrathoracic  pressure  is  raised,  it  may  be,  to  considerably  more  than 
that  of  the  atmosphere;  the  venous  return  to  the  heart  is  impeded, 
and  may  be  stopped ;  and  the  pulse  curve  is  altered  in  such  a  way  as 
to  indicate  first  an  increase  and  then  a  decrease  of  the  arterial  blood- 
pressure  succeeded  by  a  second  rise  (Fig.  132). 

Mailer's  experiment,  which  should  be  bracketed  with  Valsalva's, 
consists  in  making,  after  a  previous  expiration,  a  strong  inspiratory 
effort  with  mouth  and  nostrils  closed.  Here  the  intrathoracic  pressure 
is  greatly  diminished,  more  blood  is  drawn  into  the  chest,  and  upon  the 
whole  effects  opposite  to  those  of  Valsalva's  experiment  are  produced 
(Fig.  133).  Neither  experiment  is 
quite  free  from  danger.  In  both 
the  dicrotism  of  the  pulse  becomes 
more  marked. 


Fig.  132. — Pulse  Tracing  in  Valsalva's  Experi- 
ment (Rollett). 


133. — Pulse    Tracing    in    Mliller's 
Experiment  (Rollett). 


When  the  whole  body  is  sub- 
jected to  the  changed  pressure, 
as  in  a  balloon  or  on  a  mountain,  ^^' 
in  a  diving-bell  or  a  caisson  used 
in  building  the  piers  of  a  bridge,  the  conditions  are  very  different. 
For  the  blood-pressure,  the  intrathoracic  pressure,  and  the  intra- 
alveolar  pressure,  all  fall  together  when  the  pressure  of  the  atmo- 
sphere is  diminished,  and  all  rise  together  when  it  is  increased.  It 
is  possible  not  only  to  live,  but  to  do  hard  manual  labour,  at  very 
different  atmospheric  pressures. 

As  regards  the  chemical  effects  of  condensed  and  rarefied  air, 
Loewy  found  that  the  quantity  of  oxygen  absorbed  by  a  man  breath- 
ing air  in  the  pneumatic  cabinet  remained  constant  at  all  pressures 
between  about  two  atmospheres  and  half  an  atmosphere.  At  440  mm. 
of  mercury  dyspnoea  became  evident ;  but  if  the  person  was  now  made 
to  work,  the  dyspnoea  passed  away,  and  did  not  again  manifest  itself 


EFFECTS  OF  BREATHING  CONDENSED  AND  RAREFIED  AIR  291 

till  the  pressure  was  reduced  to  410  mm.  There  are  towns  on  the 
high  tablelands  of  the  Andes,  and  in  the  Himalayas,  where  the 
barometric  pressure  is  not  more  than  16  to  20  inches,  yet  the  in- 
habitants feel  no  ill  effects.  And  in  the  caissons  of  the  Forth  Bridge 
the  workmen  were  engaged  in  severe  toil  under  a  maximum  pressure 
of  over  three  atmospheres,  while  in  the  caissons  of  the  St.  Louis 
Bridge  in  America  a  maximum  pressure  of  over  four  atmospheres 
{i.e.,  more  than  three  atmospheres  in  addition  to  the  ordinary  air- 
pressure)  was  reached. 

Inside  the  caissons  the  men  sometimes  suffer  from  pain  and  noise  in 
the  ears,  due  to  excessive  pressure  on  the  external  surface  of  the  tym- 
panic membrane.  If  the  pressure  in  the  tympanum  is  raised  by  a 
swallowing  movement,  which  opens  the  Eustachian  tube  and  permits 
air  to  enter  it,  the  symptoms  generally  disappear. /T"he  suddenness  of 
the  change  of  pressure  has  much  to  do  with  its  effects,  and  it  is  found 
that  the  men  are  most  liable  to  dangerous  symptoms  while  passing 
through  the  air-lock  from  the  caissons  to  the  external  air.  It  may  be 
concluded,  from  experiments  on  animals,  that  some  of  the  most  serious 
of  these — the  localized  paralysis  usually  affecting  the  legs  (paraplegia) 
and  the  circulatory  disturbances— are  due  to  the  formation  of  gaseous 
emboli,  by  the  liberation  of  nitrogen  in  the  blood  and  other  body- 
fluids  when  the  pressure  is  abruptly  reduced.  And,  indeed,  it  is  found 
that  the  symptoms  can  often  be  caused  to  disappear,  both  in  animals 
and  men,  by  promptly  subjecting  them  again  to  compressed  air.  To 
avoid  gas  embolism  on  decompression,  the  shift  should  be  so  short  that 
the  body-fluids  do  not  become  fully  saturated  with  nitrogen,  and  the 
decompression  should  be  slow.  Even  with  a  rate  of  decompression  of 
twenty  minutes  for  each  atmosphere  of  excess  pressure,  the  equilibrium 
between  the  dissolved  and  the  atmospheric  nitrogen  is  not  entirely 
established  fifteen  minutes  after  decompression. 

But  that  the  action  of  air  under  a  high  pressure  is  not  merely  mechan- 
ical follows  from  the  singular  fact  that  in  pure  oxygen  at  a  pressure 
of  4  to  5  atmospheres,  which  corresponds  to  air  at  20  to  25  atmospheres, 
convulsions  are  often  produced  in  vertebrate  animals,  while  exposure 
to  6  to  25  atmospheres  of  oxygen  causes  dyspnoea  and  coma,  usually 
without  convulsions.  All  animals,  so  far  as  investigated,  are  instantly 
convulsed  and  killed  under  a  pressure  of  50  atmospheres  of  oxygen 
(Hill  and  Maclcod).  Even  seeds  and  vegetable  organisms  in  general 
are  killed  in  a  short  time  in  oxygen  at  3  to  5  atmospheres;  and  an 
atmosphere  of  pure  oxygen,  equal  to  5  atmospheres  of  air,  hinders 
the  development  of  eggs.  Lorrain  Smith  has  shown  that  in  small  birds 
and  mice  exposure  for  many  hours  to  a  pressure  of  between  i  and  2 
atmospheres  of  pure  oxygen  causes  pneumonia.  He  confirms  Bert's 
observations  on  the  acute  toxic  effects  produced  by  higher  pressures, 
and  supposes  that  in  the  production  of  caisson  disease  the  special  action 
of  the  oxygen  at  high  pressure  may  play  a  part  as  well  as  the  rapid 
decompression. 

When  the  air-pressure  is  diminished  below  a  certain  limit,  death 
takes  place  from  asphyxia,  more  or  less  gradual  according  to  the 
rate  at  which  the  pressure  is  reduced.  The  haemoglobin  cannot  get 
or  retain  enough  oxygen  to  enable  it  to  perform  its  respiratory  func- 
tion; its  dissociation  tension  is  no  longer  balanced  by  an  equal  or 


292  RESPIRA  TION 

greater  partial  pressure  of  oxygen  in  the  air.  The  tension  of  carbon 
dioxide  in  the  blood  is  also  lessened,  owing  to  the  dyspnoea  and 
the  consequent  increase  of  pulmonary  ventilation. 

To  such  changes,  as  well  as  to  the  cold,  some  of  the  deaths  in  high 
balloon  ascents  must  be  attributed.  Messrs.  Glaisher  and  Coxwell 
supposed  that  they  reached  the  height  of  37,000  feet ;  the  former  became 
unconscious  at  29,000  feet  (8,800  metres),  at  which  height  the  amount 
of  oxygen  in  the  arterial  blood  would  probably  not  exceed  10  volumes 
per  cent.,  but  recovered  during  the  descent.  The  symptoms  of  the 
'  mountain  sickness  '  so  familiar  to  Alpine  climbers  (nausea,  headache, 
and  marked  depression),  the  undue  hyperpnoea  produced  by  muscular 
exertion,  and  the  sleep  disturbed  by  irregular  breathing,  are  also  mainly 
due  to  deficiency  of  oxygen  in  the  blood.  The  most  rational  prophy- 
laxis is  to  leave  the  high  peaks  severely  alone.  But  for  the  enthusiasts 
who  cannot  do  this  a  portable  apparatus  for  generating  oxygen  has  been 
devised.  Experiments  in  the  pneumatic  cabinet  indicate  that  the 
hyperpnoea  is  due  to  the  indirect  action  of  want  of  oxygen  already 
referred  to  in  discussing  the  normal  regulation  of  respiration  (p.  275) 
— that  is,  to  the  formation,  in  consequence  of  the  insufficient  oxygen 
supply,  of  lactic  acid  or  other  substances  which  have  the  same  influence 
as  carbon  dioxide  on  the  respiratory  centre — so  that  less  carbon  dioxide 
is  required  to  excite  the  centre.  Although  the  hyperpnoea  leads  to  a 
diminution  in  the  partial  pressure  of  carbon  dioxide  in  the  pulmonary 
alveoli,  there  is  no  evidence  that  lack  of  carbon  dioxide  ('  acapnia  ')  is 
the  primary  cause  of  mountain  sickness  (Haldane).  It  must  be  remem- 
bered, however,  that  here  the  influence  of  the  low  barometric  pressure 
is  complicated  by  other  conditions.  For  example,  while  in  the  pneu- 
matic cabinet,  as  already  stated,  diminution  of  the  pressure  does  not 
affect  the  oxygen  consumption,  it  is  relatively  much  greater  on  the 
high  mountain  levels  both  during  rest  and  during  work  than  on  the 
plains.  This  is  not  the  case  in  balloon  ascents.  And  evidence  has  been 
brought  forward  that  changes  in  the  mechanics  as  well  v.s  in  the  chem- 
istry* of  respiration  are  concerned  (the  breathing,  for  instance,  taking 
on  a  periodic  character,  with  some  approach  to  the  Cheyne-Stokes  type 
— p.  282),  and  that  there  is  something  not  connected  with  the  want  of 
oxygen  which  diminishes  the  capacity  for  muscular  work.  This  '  some- 
thing '  is  perhaps  a  peculiar  excitation  of  the  nervous  system  in  the 
fierce  light  of  those  high  levels,  which  acts  not  only  on  the  retina,  but 
on  the  skin,  and  may  even  affect  the  distribution  of  the  blood.  It  is 
said  that  a  so-called  light  bath,  as  used  in  the  treatment  of  certain 
diseases,  may  increase  the  quantity  of  blood  in  rabbits  by  25  per  cent, 
in  four  hours.  The  shorter  wave-lengths  which  are  relatively  more 
intense  in  the  mountain  light  are  most  effective. 

Section  IX. — Cutaneous  Respiration. 

It  has  already  been  remarked  that  a  frog  survives  the  loss  of  its  lungs 
for  some  time,  respiration  going  on  through  the  skin.  Indeed,  it  has 
been  calculated  that  in  the  intact  frog,  under  ordinary  conditions,  as 
much  as  three-quarters  of  the  total  gaseous  exchange  may  be  cutaneous. 
Two  frogs  were  seen  to  live  thirty-three  days,  and  one  even  forty  days, 
after  excision  of  the  lungs.  The  effect  of  exclusion  of  the  pulmonary 
respiration  on  the  gaseous  exchange  depends  on  the  previous  intensity 
of  the  metabolism.  If  this  is  high  the  gaseous  exchange  sinks  markedly ; 
if  it  is  low  there  is  scarcely  any  alteration.     At  their  maximum  efficiency 


CUTANEOUS  RESPIRATION  293 

the  frog's  lungs  are  capable  of  sustaining  a  much  greater  exchange 
thaji  tlic  skin.  Besides  this  quantitative,  there  is  a  qualitative  differ- 
ence, the  carbon  dioxide  passing  more  easily  through  the  skin  than  the 
oxygen,  so  that  the  respiratory  quotient  is  increased  by  elimination  of 
the  lungs.  In  mammals  the  structure  of  the  skin  is  different,  and 
respiration  can  only  go  on  through  it  to  a  very  slight  extent.  The 
amount  of  carbon  dioxide  excreted  in  man,  although  only  about  4  grm. 
or  2  litres  in  twenty-four  hours,  is  much  greater  than  corresponds  to 
the  quantity  of  oxygen  absorbed  through  the  skin.  It  has  been  as- 
serted, and  no  doubt  with  justice,  that  some  at  least  of  the  carbon 
dioxide  given  off  is  due  to  putrefactive  processes  taking  place  on  the 
surface  of  the  body.  Such  processes,  as  has  already  been  pointed  out, 
seem  also  responsible  in  part  for  the  heavy  odour  of  a  '  close  '  room. 
For  no  Iiarmful  products  appear  to  be  exhaled  from  the  skin  when  it  is 
properly  cleansed.  In  spite  of  the  romantic  statements  to  the  con- 
trary in  ancient  and  modem  books  (for  instance,  the  story  of  the  child 
that  was  gilded  to  play  the  part  of  an  angel  at  the  coronation  of  a 
medieval  pope,  but  died  before  the  ceremony  began),  the  whole  of  the 
human  skin  may  be  coated  with  an  impermeable  varnish  without  any 
jjl  effects.  The  entire  surface  of  the^  body  of  a  patient  with  cutaneous 
disease  was  covered  with  tar,  and  kept  covered  for  ten  days.  There  was 
not  the  least  disturbance  of  any  normal  function.  The  serious  effects 
of  varnishing  the  skin  in  animals  are  due,  not  to  retention  of  poisonous 
substances,  but  to  increased  heat  loss.  Varnishing  is  not  so  rapidly 
harmful  in  large  animals  like  dogs  as  in  rabbits,  which  have  a  relatively 
great  surface  and  a  delicate  skin.  The  danger  of  widespread  superficial 
bums  is  well  known.  But  it  is  not  due  to  diminished  excretion  by  the 
skin,  for  death  occurs  when  large  cutaneous  areas  remain  uninjured. 
The  patient  nearly  always  dies  when  a  quarter  of  the  whole  skin  is 
burnt;  yet  the  remaining  tLree-quarters  may  surely  be  considered 
capable,  from  all  analogy,  of  making  up  the  loss  by  increased  activity. 
One  kidney  is  enough  to  eliminate  the  products  of  the  nitrogenous 
metabolism  of  the  whole  body.  It  is  difficult  to  see  why  the  excretion 
of  the  trifling  amount  of  solid  matter  in  the  perspiration  should  be 
interfered  with  by  the  loss  of  25  per  cent,  of  the  sweat-glands.  The  real 
explanation  of  the  serious  effects  of  extensive  superficial  bums  is 
perhaps  the  excessive  irritation  of  the  sensory  nerves,  which  may  lead 
to  changes  in  the  nervous  centres,  or  reflexly  in  other  organs,  or  the 
chemical  changes  in  the  damaged  tissue,  for  example,  in  the  blood- 
corpuscles,  or  the  transudation  of  lymph  at  the  injured  part,  and  con- 
sequent increase  in  the  concentration  of  the  blood. 


PRACTICAL  EXERCISES  ON  CHAPTER  IV. 

I.  Tracing  of  the  Respiratory  Movements  in  Man. — Pass  a  tape 
through  the  rings  B  of  the  stcthograph  shown  in  Fig.  134,  and 
then  around  the  neck  or  over  the  shoulders,  so  as  to  support  the 
instrument  on  the  chest  at  a  convenient  height.  Fasten  tapes  to  the 
hooks  and  tic  them  by  a  slip-knot  round  the  chest.  The  tube  E  is 
connected  to  a  recording  tambour,  writing  on  a  drum.  Or  use  the  belt 
stcthograph  or  spirograph  of  Fitz  (p.  232),  fastening  the  clastic  tube 
round  the  chest  with  the  chain,  and  connecting  it  with  a  tambour  or 
the  bellows  recorder  shown  in  Fig.  137.  Compare  the  extent  of  the 
excursion  when  the  tube  is  adjusted  at  different  levels  over  the  thorax 
and  abdomen. 


294  RESPIRA  TION 

2*  Production  of  Apnoea  and  Periodic  Breathing  in  Man. — Arrange 
for  taking  tracings  of  the  respiratory  movements  from  a  fellow-student 
as  in  I.  Let  the  subject  of  the  experiment  recline  in  a  perfectly  easy 
position  in  an  armchair.  Let  him  then  breathe  deeply  and  frequently 
for  about  two  minutes,  so  as  to  produce  a  prolonged  apnoea  of  about 
two  minutes'  duration.  Whenever  any  desire  to  breathe  returns,  the 
breathing  is  to  be  allowed  to  take  its  own  course.  It  may  be  expected 
at  first  to  be  of  the  periodic  (Cheyne- Stokes)  type. 

3.  Tracing  of  the  Respiratory  Movements  in  Animals. — (a)  Set  up 
the  arrangement  shown  in  Fig.  135,  and  test  whether  it  is  air-tight. 
Have  also  in  readiness  an  induction  machine  and  electrodes  arranged 
for  an  interrupted  current.  Anaesthetize  a  rabbit  with  chloral  or 
ether  (p.  216),  or  a  small  dogf  with  morphine  and  ether,  or  A.C.E. 
mixture.  Insert  a  cannula  into  the  trachea  (p.  199),  and  connect  it 
with  the  large  bottle  by  a  tube.     Connect  the  bottle  with  a  recording 


Fig.  134. — Stethograph. 


tambour  adjusted  to  write  on  a  drum,  and  regulate  the  amount  of  the 
excursion  of  the  lever  by  slackening  or  tightening  the  screw-clamp. 
Set  the  drum  off  at  slow  speed,  and  take  a  tracing. 

{b)  Then  disconnect  the  cannula  from  its  tube.  Dissect  out  the 
vagus  in  the  lower  part  of  the  neck,  pass  a  ligature  under  it,  but  do  not 
tie  it.  Connect  the  cannula  again  with  the  bottle,  and  while  a  tracing 
is  being  taken  ligature  the  vagus.  Cut  below  the  ligature  and  stimulate 
its  central  end  with  weak  shocks,  marking  the  time  of  stimulation  on 
the  drum.  Repeat  the  stimulation  with  strong  shocks,  and  observe 
the  results. 

(c)  Apply  a  strong  solution  of  potassium  chloride  with  a  camel' s- 
hair  brush  to  the  central  end  of  the  vagus  while  a  tracing  is  being  taken, 
and  observe  the  effect. 

*  This  experiment  is  only  to  be  attempted  under  the  direct  supervision  of 
the  demonstrator. 

t  If  a  large  dog  is  used  the  bottle  should  be  omitted,  the  tracheal  cannula 
being  connected  with  the  stem  of  a  T-tube.  One  end  of  the  horizontal  limb 
of  the  T-tube  is  connected  with  the  tambour;  the  other  is  provided  with  a 
rubber  tube,  which  can  be  partially  closed  by  a  screw-clamp  to  regulate  the 
excursion.  Ether  may  be  given  when  required  by  connecting  the  horizontal 
hmb  of  the  T-tube  with  a  bottle  with  two  glass  tubes  in  the  cork  (p.  199). 


PRACTICAL  EXERCISES 


295 


(d)  Isolate  the  sciatic  nerv^c  (p.  210),  ligature  it,  and  cut  below  the 
ligature.  Stimulate  its  central  end  while  a  tracing  is  being  taken. 
The  respiratory  movements  will  be  increased. 

(e)  Disconnect  the  cannula,  and  isolate  the  vagus  on  the  other  side. 
Wliile  a  tracing  is  being  taken,  divide  it.  The  respiratory  movements 
will  probably  at  once  become  deeper  and  less  frequent. 

(J)  Again  disconnect  the  cannula.  Isolate  the  superior  laryngeal 
branch  of  the  vagus.  This  will  be  found  entering  the  larynx  at  the 
point  where  the  laryngeal  horn  of  the  hyoid  bone  is  connected  with  the 
thyroid  cartilage.     If  the  finger  is  passed  back  along  the  upper  border 


J'racheal    Cann.vLLa 


or  '^^,,re  <■" 


Fig 


135. — Arrangemc.it  for  Respiratory  Tracing.  Two  glass  tubes  are  inserted 
through  a  cork  in  the  mouth  of  the  large  bottle.  One  of  them  has  a  small  piece  of 
indiarubber  tubing  on  it,  which  is  closed  or  opened,  as  may  be  required,  by  a 
screw-clamp.  The  other  is  connected  by  a  rubber  tube  with  a  recording  tambour. 
The  tubulure  at  the  bottom  of  the  bottle  is  closed  by  a  cork,  through  which 
passes  a  glass  tube,  connected  by  a  rubber  tube  with  the  tracheal  cannula.  If 
no  bottle  with  tubulure  is  available,  it  is  only  necessary  to  pass  through  the  cork, 
down  to  the  bottom  of  the  bottle,  a  third  glass  tube,  which  is  connected  with  the 
tracheal  cannula.  While  a  tracing  is  being  taken  the  animal  breathes  the  air 
contained  in  the  bottle.  When  this  becomes  vitiated  the  respiratory  movements 
are  exaggerated  and  a  normal  tracing  is  no  longer  obtained.  For  this  reason 
the  tracheal  cannula  must  be  connected  with  the  bottle  only  at  the  moment 
when  a  tracing  is  to  be  taken.  The  arrangement  is  most  suitable  for  a  small 
animal. 


of  the  thyroid  cartilage,  this  point  will  easily  be  felt.  Ligature  the 
nerve,  and  divide  it  between  the  larynx  and  the  ligature.  Reconnect 
the  cannula.  Take  a  tracing  first  with  weak,  and  then  with  strong 
stimulation  of  the  central  end  of  the  superior  laryngeal. 

(1?)  Make  an  incision  through  the  abdominal  wall  in  the  linea  alba, 
and  study  the  movements  of  the  diaphragm.  Find  the  nerves  from 
which  the  phrenics  take  origin  in  the  neck.  In  the  dog  they  arise  from 
the  fifth,  sixth,  and  seventh  cervical  nerves.  Divide  the  phrenic  fibres 
on  one  side,  and  observe  that  the  diaphragm  on  the  corresponding  side 
is  now  paralyzed. 


296 


RESPIRA  TION 


(h)  Insert  a  cannula  into  the  carotid  artery.  While  a  respiratory 
tracing  is  being  taken,  allow  blood  to  flow  from  the  artery.  Dyspnoea 
and  exaggeration  of  the  respiratory  movements  will  be  seen  when  a 
considerable  quantity  of  blood  has  been  lost.  Mark  and  varnish  the 
tracings. 

In  the  whole  of  this  experiment  the  tracheal  cannula  is  to  be  dis- 
connected, except  when  the  lever  is  actually  writing  on  the  drum,  in 
order  that  the  period  during  which  the  animal  must  breathe  into  the 
confined  space  of  the  bottle  may  be  diminished  as  much  as  possible. 
Instead  of  the  method  described,  the  stethograph  shown  in  Fig.  136 
may  be  used  to  obtain  respiratory  tracings  from  animals,  a  broad  canvas 
band  being  put  round  the  animal's  chest.  To  each  end  of  this  band  is 
clamped  with  sufficient  tension  a  strong  thread  (F),  fastened  to  a  small 
metal  disc  on  the  inside  of  the 
rubber  dam  closing  the  obliquely- 
cut  ends  of  the  metal  cylinder  D. 
The  tube  G  is  connected  with  a 
tambour  or  with  a  bellows  recorder 
(Fig.  137). 

4.  The  Effect  of  Temperature  on 
the  Respiratory  Centre— Heat  Dysp- 
noea.— Set  up  an  arrangement  for 


Fig.  136. — Stethograph  (Crile). 


Fig.  137. — Bellows  Recorder.  B,  a 
lead  tube  connected  with  the 
small  bellows  A,  which  consists  of 
a  light  wooden  base  and  top,  to 
which  is  cemented  very  flexible 
(organ  key)  leather,  properly 
creased  for  expansion  and  con- 
traction; C,  writing  lever. 


taking  a  respiratory  tracing  as  in  2 
(footnote,  p.  294).  Anaesthetize  a 
dog,  and  fasten  it,  back  downward, 
on  a  holder.  Make  an  incision  in 
the  middle  line  of  the  neck,  com- 
mencing a  little  below  the  cricoid 
cartilage,  and  extending  down  for 
4  or  5  inches.  Insert  a  cannula  into  the  trachea.  Isolate  both  carotid 
arteries  for  as  great  a  distance  as  possible,  and  arrange  them  on  the 
brass  tubes  shown  in  Fig.  138.  Connect  two  adjacent  ends  of  the 
tubes  by  a  short  rubber  tube.  Connect  one  of  the  remaining  ends  to  a 
funnel,  supported  on  a  stand,  and  the  other  to  a  rubber  tube  hanging 
over  the  table  above  a  large  jar.  Slip  two  or  three  folds  of  paper 
between  the  tubes  and  the  vagus  nerves.  Heat  two  or  three  litres  of 
water  to  about  65°  C.  (a)  Now  connect  the  tracheal  cannula  with  the 
tambour.  As  soon  as  the  tracing  is  under  way,  let  the  hot  water  run 
through  the  funnel  and  tubes  into  the  jar.  Mark  on  the  tracing  the 
point  at  which  the  flow  of  the  hot  water  was  begun,  and  go  on  passing 
it  until  it  has  produced  an  effect.  Then  stop  the  drum,  and  circulate 
water  at  the  ordinary  temperature  till  the  breathing  is  again  normal. 
Then,  while  a  tracing  is  being  taken,  pass  ice-cold  water  through  the 
tubes,  and  again  notice  the  effect. 


PRACTICAL  EXERCISES 


297 


(b)  Expose  the  sciatic.  Pass  ice-water  through  the  tubes,  and  wliilc 
a  respiratory  tracing  is  being  taken  stimulate  its  central  end  with  in- 
duction shocks  so  weak  as  just  to  cause  an  effect.  Pass  water  at  air 
temperature  through  the  tubes,  and  repeat  the  stimulation  with  the 
coils  at  the  same  distance.  Do  the  same  while  hot  water  is  being  passed 
through  the  tubes,  and  compare  the  results.  Always  allow  the  water 
to  pass  for  a  time  before  making  an  observation. 

5.  Measurement  of  Volume  of  Air  inspired  or  expired — Vital  Capacity. 
— A  spirometer  (Fig.  114,  p.  234)  of  suiticient  accuracy  for  this  experi- 
ment can  be  made  by  removing  the  bottom  of  a  large  bottle  with  a 
capacity  of  not  less  than  4  litres.  A  good  cork,  through  which  passes 
a  glass  tube  connected  with  a  rubber  tube,  is  fitted  into  the  neck.  The 
bottle  is  fixed  vertically,  mouth  downwards,  the  glass  tube  being  closed 
for  the  time,  and  graduated,  by  pouring  in  measured  quantities  of  water, 
say  100  c.c.  at  a  time,  and  marking  the  level.  The  divisions  arc  then 
etched  in.  If  the  cork  docs  not  fit  air-tight,  it  is  covered  with  wax. 
The  bottle  is  swung  on  two  pulleys,  counterpoised  and  immersed, 
bottom  down,  in  a  large 
glass  jar  or  a  small  cask 
nearly  full  of  water.  A 
smaller  bottle  may  be  used 
for  the  determination  of  the 
tidal  air,  so  as  to  reduce  the 
error  of  reading. 

(i)  Submerge  the   bottle  -^ 

to  the  stopper,  afteropening    Fig.   138.— Arrangement  for  Heating  or  Cooling 


the  pinchcock  on  the  rub- 
ber tube.  Breathe  into  the 
bottle,  close  the  cock,  ad- 
just the  bottle  so  that  the 
level  of  the  water  is  the 
same  inside  and  outside, and 
then  read  off  the  level.  De- 
termine the  volume  of  air 
expired  in — 

(a)  A  normal  expiration 
after  a  normal  inspiration 
(tidal  air) ; 

{b)  The    greatest    possible 


the  Blood  in  the  Carotid  Arteries.  A,  cylin- 
drical portion  of  tube;  B,  flattened  portion  in 
the  groove,  between  which  and  A  the  artery 
lies;  C,  cross-section,  showing  the  lumen  extend- 
ing into  B ;  D,  rubber  tube  attached  to  a  brass 
tube  soldered  into  A.  The  other  end  of  A  has 
a  similar  brass  tube  soldered  into  it  (not  shown 
in  the  figure).  This  is  connected  by  a  rubber 
tube  with  a  similar  apparatus,  on  which  the 
other  carotid  lies.  D  is  connected  with  a  funnel 
containing  hot  or  cold  water  or  with  the  outflow 
tube,  as  the  case  may  be. 


expiration    after    a    normal    inspiration 
after    the    greatest    possible 


(supplemental  air  plus  tidal  air 

(c)  The    greatest    possible    expiration 
inspiration  (vital  capacity). 

(2)  Open  the  cock  and  raise  the  bottle  till  it  is  nearly  full  of  air. 
Determine  the  volume  of  air  inspired  in — 

(a)  A  normal  inspiration  after  a  normal  expiration  (tidal  air) ; 

(6)  The  greatest  possible  inspiration  after  a  normal  expiration 
(complemental  air  plus  tidal  air) ; 

(c)  The  greatest  possible  inspiration  after  the  greatest  possible 
expiration  (vital  capacity). 

Make  several  observations  of  each  quantity,  and  take  the  mean. 

(3)  Count  the  rate  of  respiration  for  three  minutes,  keeping  the 
breathing  as  nearly  normal  as  possible;  repeat  the  observation;  and 
from  the  mean  result  and  the  amount  of  the  tidal  air  calculate  the 
quantity  of  air  taken  into  the  lungs  in  twenty-four  hours  (pulmonary 
ventilation). 

6.  Cardio-Pneumatic  Movements.  —  Fill  a  U-tube  with  tobacco- 
smoke.     One  end  of  the  tube  is  placed  in  the  nostril  of  a  fellow-student. 


298  RESPIRA  TION 

and  made  tight  with  a  little  cotton-wool.  The  other  nostril  and  the  mouth 
are  closed,  and  respiration  suspended.  The  column  of  smoke  moves 
in  and  out  at  each  beat  of  the  heart.  By  feeling  the  apex-beat,  try  to 
verify  the  fact  that  during  systole  the  cardio-pneumatic  movement  is 
inspiratory,  and  in  diastole  expiratory. 

7.  Auscultation  of  the  Lungs. — This  is  taught  in  the  course  of  physical 
diagnosis,  but  in  connection  with  the  subject  the  student  may  perform 
the  following  experiment  on  a  dog  used  for  some  other  purpose :  Open 
the  trachea  as  described  on  p.  199.  Insert  into  it  the  cross-piece  of  a 
glass  T-tube  of  as  large  a  bore  as  possible,  tying  the  trachea  over  it  on 
each  side  of  the  stem.  The  stem  projecting  from  the  wound  is  armed 
with  a  short  piece  of  rubber  tubing,  which  can  be  closed  at  will  with  a 
clip.  When  the  tube  is  thus  closed  the  animal  breathes  through  the 
glottis  in  the  ordinary  way.  When  the  tube  is  open,  and  the  mouth 
and  nose  covered  tightly  with  a  cloth,  no  air  goes  through  the  glottis. 
The  tube  being  closed,  listen  with  the  stethoscope  or  the  ear  alone  over 
a  part  of  the  chest  where  the  vesicular  murmur  is  well  heard.     If  the 


Fig.  139. — Haldane's  Apparatus  for  measuring  the  Quantity  of  CO3  and  Aqueous 
Vapour  given  off  by  an  Animal.  A,  chamber  into  which  the  animal  is  put; 
I  and  4,  WoulfE's  bottles  filled  with  soda-lime  to  absorb  carbon  dioxide;  2,  3,  and 
5,  Woulff's  bottles  filled  with  pumice-stone  soaked  in  sulphuric  acid  to  absorb 
watery  vapour;  B,  glass  bell-Jar  suspended  in  water,  by  means  of  which  the 
negative  pressure  is  known ;  P,  water-pump  which  sucks  air  through  the  appar- 
atus; I  and  2  are  simply  for  absorbing  the  carbon  dioxide  and  water  of  the 
ingoing  air. 

rubbing  of  the  hairs  below  the  stethoscope  causes  disturbing  sounds, 
shave  a  portion  of  the  skin.  Continue  listening  while  an  assistant 
closes  the  tube  and  covers  up  the  animal's  muzzle.  Determine  whether 
any  change  takes  place  in  the  vesicular  sound. 

Repeat  the  observation  while  listening  over  the  lower  part  of  the 
trachea,  and  determine  whether  any  change  takes  place  in  the  bronchial 
breathing  sound. 

8.  Respiratory  Pressure. — Connect  a  strong  rubber  tube  with  a  glass 
bulb,  and  the  bulb  with  a  mercurial  manometer  provided  with  a  scale, 
(i)  Fasten  the  tube  with  a  little  cotton-wool  in  one  nostril,  breathe 
through  the  other  with  closed  mouth,  and  observe  the  amount  by  which 
the  level  of  the  mercury  is  altered  in  ordinary  inspiration  and  ex- 
piraton. 

(2)  Rep:at  the  observation  with  forced  breathing,  pinching  the  tube 
at  the  height  of  inspiration  and  expiration,  and  reading  off  the  maximum 
inspiratory  and  expiratory  pressure. 


PRACTICAL  EXERCISES 


299 


(3)  Repeat   (i)   with  the  tube  connected  to  the  moutli   by  a   glass 
tube  held  between  the  lips,  and  the  nostrils  op>en. 

(4)  Repeat  (2)  with  the  tube  in  the  mouth  and  the  nostrils  closed. 

9-  Estimation  of  the  Quantity  of  Water  and  of  Carbon  Dioxide  given 
off  by  an  Animal  {Haldane's  Method). — (i)  Connect  the  apparatus 
shown  in  Fig.  139  with  the  water-pump.  Allow  a  negative  pressure 
of  5  or  6  inches  of  water  to  be  established  in  it,  as  shown  by  the  rise  of 
water  in  the  bell-jar  B.  Then  close  the  open  tube  of  carbon  dioxide 
bottle  I,  and  clamp  the  tube  between  the  water-pump  and  the  bell-jar. 
If  the  negative  pressure  is  maintained,  the  arrangement  is  air-tight. 
Now  weigh  bottle  3  and  bottles  4  and  5,  the  last  two  together.  Place 
a  cat  in  the  respiratory  chamber  A,  connect  the  chamber  directly  with 
the  water-pump,  and  test  whether  it  is  tight.  Then  take  the  stopper 
out  of  bottle  I,  and  adjust  the  rate  at  which  air  is  drawn  through  the 
apparatus.  Let  the  ventilation 
go  on  for  a  few  minutes,  then 
insert  bottles  3,  4,  and  5  again. 
Note  the  time  exactly  at  this 
point,  and  after  an  hour  dis- 
connect 3,  4,  and  5,  and  again 
weigh.  The  difference  of  the 
two  weighings  of  3  shows  the 
quantity  of  welter  given  off  by 
the  animal  in  an  hour ;  the  dif- 
ference in  the  combined  weight 
of  4  and  5,  the  quantity  of 
carbon  dioxide.  Weigh  the  cat, 
and  calculate  the  amount  of 
water  and  of  carbon  dioxide 
given  off  per  kilo  per  hour. 

{2)  For  the  student  it  is 
more  convenient  to  use  smaller 
animals.  The  mouse  may  be 
taken  as  an  example  of  a 
warm-blooded  animal,  and  the 
frog  of  a  cold-blooded.  Instead 
of  the  Woulff' s  bottles  use  wide 
test  -  tubes  connected  as  in 
Fig.  140,  and  for  the  animal 
chamber  a  small  beaker,  closed 
with    a    very    carefully    fitted 

cork  which  has  been  boiled  in  paraffin.  The  inlet  and  outlet  tubes  of 
the  chamber  are  to  be  introduced  through  this  cork.  The  holes  for  these 
are  to  be  bored  with  the  greatest  care,  and  the  tubes  to  be  put  in  while 
the  cork  is  still  hot  from  boiling  in  paraffin.  Also  insert  a  thermom- 
eter about  6  inches  long  registering  from  0°  C.  to  45°  C.  Modeller's 
wax  is  to  be  used  finally  to  render  all  the  junctions  air-tight. 

Add  to  the  series  of  tubes  described  in  the  apparatus  a  single  tube 
containing  baryta-water.  This  is  placed  to  the  left  of  tube  5,  and  so 
arranged  that  the  air-current  bubbles  through  the  water.  As  long 
as  the  absorption  of  carbon  dioxide  is  complete,  the  baryta-water 
remains  clear.  Beyond  this  a  water-bottle  should  be  placed  to  act 
as  a  valve  and  to  indicate  the  negative  pressure  in  the  apparatus.  It 
can  be  most  simply  constructed  by  using  a  cylinder  of  stout  glass 
tubing  in  a  widc-moiithcd  bottle  containing  some  water,  the  inlet  and 
outlet  tubes  passing  through  a  paraffined  cork  which  seals  the  upper 
end  of  the  cylinder. 


Fig.  140. — Absorption  Tubes  for  CO.^  and 
Moisture.  A,  soda  -  lime  tube;  B,  [sul- 
phuric acid  tube;  C,  wooden  freune!  in 
which  A  and  B  are  supported  by  wires  d  ; 
>,  wire  hook,  which  grips  the  glass  tube 
firmly,  and  by  means  of  which  the  tubes 
are  lifted  out  of  the  frame  in  order  to  be 
weighed;  a,  short  piece  of  glass  tubing, 
by  taking  out  wliich  the  absorption  tubes 
are  disconnected  from  the  rest  of  the 
apparatus;  e,  glass  tube  going  ofE  to  animal 
cliamber. 


300 


RESPIRA  TION 


Before  making  an  observation,  test  whether  the  apparatus  is  air- 
tight, as  explained  above,  after  introducing  the  animal  into  the  cham- 
ber, sealing  the  latter  with  wax,  and  connecting  it  with  the  absorption- 
tubes.  But  a  negative  pressure  of  2  or  3  inches  of  water  is  a  sufficient 
test  for  the  small  apparatus. 

To  make  an  observation,  set  the  air-current  going  at  the  desired 
i-ate.  Allow  it  to  run  for  a  few  minutes  till  the  carbon  dioxide,  which 
has  accumulated  during  the  testing,  has  been  swept  out.  At  a  time 
which  has  been  decided  on  and  noted,  stop  the  current  b}-  disconnecting 
the  water-pump.  Disconnect  and  stopper  up  the  animal  chamber,  and 
weigh  it  as  quickly  as  possible.  Connect  up  again,  using  only  recently- 
weighed  absorption-tubes,  and  finally  connect  with  the  water-pump 
and  allow  the  current  to  pass  for  a  definite  period,  say  an  hour. 

The  soda-lime  should  not  be  too  dr5%  or  absorption  is  not  sufficiently 
rapid.  The  following  facts  are  made  out :  (a)  Loss  of  weight  by  the 
animal  chamber  (chiefly  loss  by  the  animal) ;  [b)  gain  of  the  sulphuric 
acid  tube  in  water;   \c)  gain  of  the  soda-lime  tubes  in  carbon  dioxide. 

The  total  loss  and  total  gain  do  not  correspond,  the  gain  being  always 
greater  than  the  loss.  The  surplus  can  only  be  oxygen  absorbed  by  the 
animal  and  added  to  the  hydrogen  and  carbon  of  its  substance  to  form 
water  and  carbon  dioxide.     Calculate  the  respirators-  quotient  (p.  240). 

10.  Muscular  Contraction  in  the  Absence  of  Free  Oxygen  (sec  p.  265). 
— Pith  a  frog  (brain  and  cord).  Cut  off  one  hind-leg  at  the  middle 
of  the  thigh,  and  strip  the  skin  from  it.  Pass  a  thread  under  the  tendo 
Achillis,  tie  it,  and  di\"ide  the  tendon  below  :t.  Free  the  tendon  and 
the  gastrocnemius  muscle  from  the  loose  connective  tissue  lying  between 
them  and  the  bones  of  the  leg.  and  divide  the  latter  just  below  the  knee. 
Remove  superfluous  thigh  muscles,  and  fasten  the  gastrocnemius  in 
a  moist  chamber  by  means  of  the  femur.  Attach  the  thread  on  the 
tendon  to  a  lever.  Connect  the  poles  of  the  secondars-  coil  of  an  induc- 
tion machine  by  fine  copper  wir«-s  to  the  femur  and  the  tendon.  Put 
a  battery  and  simple  key  in  the  primary,  and  arrange  it  for  single  shocks. 
Stimulate  the  muscle  and  obser\-e  the  height  of  the  contraction.  Now 
pass  into  the  chamber  a  current  of  washed  hydrogen  gas  from  a  bottle 
containing  granulated  zinc,  upon  which  a  little  dilute  sulphuric  acid 
is  poured  from  time  to  time.  The  air  in  the  moist  chamber  will  soon 
be  entirely  displaced  by  the  hydrogen,  but  the  muscle  will  contract  on 
being  stimulated,  and  the  stimulation  can  be  repeated  many  times. 

11.  Oxidizing  Ferments. — Wash  out  the  bloodvessels  of  a  dog  or 
rabbit  (Practical  Exercises,  p.  65).  Chop  up  finely  portions  of  pancreas, 
spleen,  muscle,  lungs,  and  Mdney,  keeping  each  separate,  and  avoiding 
any  contamination  of  one  by  another.  Grind  up  half  of  each  portion 
with  sand  in  a  small  mortar,  and  extract  v/ith  a  small  quantity  of  water, 
keeping  all  the  extracts  separate.  Into  each  of  eleven  test-tubes  put 
10  c.c.  of  a  colourless  dilute  alkahne  solution  of  paraphenylenediamin 
and  a-naphthol  (freshly  made  by  mixing  solutions  of  the  two  sub- 
stances in  cquimolccular  proportions*  and  adding  a  little  sodium 
carbonate).  To  five  of  the  tubes  add  the  chopped  organs,  to  five  the 
watery  extracts  of  the  organs,  and  enough  water  to  make  the  volume 
enual  in  all  the  tubes.  To  the  remaining  tube  add  the  same  amount 
of  water.     Observe  in  which  tube  a  change  of  colour  takes  place  (p.  268). 

*  I.e.,  the  weight  of  each  of  the  two  substances  in  the  mixture  should  be 
proportional  to  its  molecular  weight.  A  convenient  solution  contains  0144 
per  cent,  of  a-naphthol  and  o'loS  pei  cent,  of  paraphenylenediamin.  These 
quantities  are  one-hundredth-molecular.  Sod  um  carbonate  is  added  to  the 
amount  of  025  per  cent.  The  o-naphthol  can  be  kept  as  a  i  per  cent,  solu- 
tion in  50  per  ceiit.  alcohol. 


CHAPTER  V 
VOICE  AND  SPEECH 

Voice. — Sounds  of  various  kinds  are  frequently  produced  by  the 
movements  of  animals  as  a  whole,  or  of  individual  organs.  The 
muscular  sound,  the  sounds  of  the  heart  and  of  respiration,  we  have 
already  had  to  speak  of.  Such  sounds  may  be  considered  as  purely 
accidental  as  the  footfall  of  a  man  or  the  buzzing  of  a  fiy.  The 
wings  of  an  insect  beat  the  air,  not  to  cause  soimd,  but  to  produce 
motion;  the  respiratory  murmur  is  a  mere  indication  that  air  is 
finding  its  way  into  the  lungs,  it  is  in  no  way  related  to  the  oxidation 
of  the  blood  in  the  pulmonary'  capillaries.  But  in  many  of  the 
higher  animals  mechanisms  exist  which  are  specially  devoted  to  the 
utterance  of  sounds  as  their  prime  and  proper  end.  In  man  the 
voice-producing  mechanism  consists  of  a  triple  series  of  tubes  and 
chambers:  (i)  The  trachea,  through  which  a  blast  of  air  is  blown; 
(2)  the  larynx,  with  the  vocal  cords,  by  the  vibrarions  of  which 
sound-waves  are  set  up ;  and  (3)  the  upper  resonance  chambers,  the 
pharjTix,  mouth,  and  nasal  ca\'ities,  in  which  the  sounds  produced 
in  the  lar^mx  are  modified  and  intensified,  and  in  which  independent 
notes  and  noises  arise. 

The  larynx  is  a  cartilaginous  box,  across  which  are  stretched, 
from  front  to  back,  two  thin  and  sharp-edged  membranes,  the  (true) 
vocal  cords.  In  front  the  cords  are  attached  to  the  thyroid  carti- 
lage, one  a  little  to  each  side  of  the  middle  Une;  behind  they  are 
connected  to  the  vocal  or  anterior  processes  of  the  pyramidal 
arytenoid  cartilages.  The  thyroid  and  the  two  arytenoids  are 
mounted  upon  a  cartilaginous  ring,  the  cricoid.  The  arytenoids 
can  rotate  on  the  cricoid  about  a  vertical  axis,  while  the  cricoid  can 
rotate  on  the  thyroid  cartilage  around  a  transverse  horizontal  axis. 
The  cricoid  can  thus  be  raised  by  the  contraction  of  the  crico- 
thyroid muscle,  and  the  vocal  cords  stretched.  By  the  pull  of  the 
posterior  crico-arytenoid  muscles,  attached  to  the  external  or  mus- 
cular processes  of  the  arytenoid  cartilages,  the  vocal  processes  are 
rotated  outwards,  the  cords  separated  from  each  other  or  abducted, 
and  the  chink  between  them,  the  rima  glottidis,  widened.  When 
the  vocal  processes  are  approximated  by  contraction  of  the  lateral 

301 


302 


VOICE  AND  SPEECH 


crico-arytenoid  muscles  and  the  consequent  forward  movement  of 
the  muscular  processes,  the  vocal  cords  are  brought  close  together, 
or  addiided,  and  the  rima  is  narrowed.  The  transverse  or  posterior 
arytenoid  muscle,  which  connects  the  two  arytenoid  cartilages 
behind,  also  helps,  by  its  contraction,  to  narrow  the  glottis  by  shift- 
ing the  cartilages  on  their  articular  surfaces  somewhat  nearer  the 
middle  line.  Running  in  each  vocal  cord,  and,  in  fact,  incorporated 
with  its  elastic  tissue,  is  a  muscle,  the  th}TO-arytenoid,  the  external 
portion  of  which  may  to  some  extent  cause  inward  rotation  of  the 
vocal  processes  and  adduction  of  the  cords;  but  the  main  function, 
at  least  of  its  inner  part,  is  to  alter  the  tension  of  the  cords.  The 
diagrams  in  Figs.  141  and  142  illustrate  the  action  of  the  abductors 
and  adductors  of  the  vocal  cords. 

The  crico-thyroid  muscle  and  the  deflectors  of  the  epiglottis  are 
supplied  by  the  superior  laryngeal  branch  of  the  vagus,  which  also 


Fig.  141. — Diagrammatic  Hori- 
zontal Section  of  Larynx  to 
show  the  Direction  of  Pull  of 
the  Posterior  Crico-Arytenoid 
Muscles,  which  abduct  the 
Vocal  Cords.  Dotted  lines 
show  position  in  abduction. 


Fig.  142. — Direction  of  Pull' of 
the  Lateral  Crico-Arytenoids, 
which  adduct  the  Vocal 
Cords.  Dotted  lines  show 
position  in  adduction. 


contains  the  sensory  fibres  for  the  mucous  membrane  of  the  larynx 
above  the  vocal  cords.  In  the  dog  and  rabbit  motor  fibres  also  reach 
the  crico-thyroid  by  the  so-called  middle  laryngeal  nerve  which 
arises  from  the  superior  pharyngeal  branch  of  the  vagus.  All  the 
other  intrinsic  muscles  are  supplied  by  the  recurrent  laryngeal 
branch  of  the  vagus.  It  receives  these  motor  fibres  from  the  spinal 
accessory,  and  supplies  sensory  fibres  to  the  mucous  membrane  of 
the  larynx  below  the  vocal  cords  and  to  the  trachea. 

The  voice  is  produced,  like  the  sounds  of  a  reed  instrument,  by 
the  rhythmical  interruption  of  an  expiratory  blast  of  air  by  the 
vibrating  vocal  cords.  When  a  bell  is  struck,  vibrations  are  set  up 
in  the  metal,  which  are  communicated  to  the  air.  It  is  not  the  same 
with  the  vibrations  of  the  vocal  cords;  if  they  were  plucked  or 
struck,  they  would  only  produce  a  feeble  note.  The  air  in  the 
mouth,  pharynx,  larynx,  trachea,  and  lungs  is  the  real  sounding 


VOICE  303 

body;  a  pulse  of  alternate  rarefaction  and  condensation  is  set  up  in 
it  by  the  interference,  at  regular  intervals,  of  the  vocal  cords  with 
the  expiratory  blast.  Forced  abruptly  from  their  position  of  equi- 
Hbrium  as  the  blast  begins,  they  almost  immediately  regain  and 
pass  below  it,  in  virtue  of  their  elasticity,  and  continue  to  vibrate  as 
long  as  the  stream  of  air  continues  to  issue  in  sufficient  strength. 
Not  only  do  they  vibrate  up  and  down,  but  also  towards  and  away 
from  the  middle  line,  so  that,  at  least  in  the  chest  voice,  they  come 
•into  contact  with  each  other  at  each  swing.  The  sound-waves  thus 
set  up  spread  out  on  every  side,  impinge  on  the  tympanic  membrane, 
set  it  quivering  in  response,  and  give  rise  to  the  sensatio;i  of  sound. 
We  may  say,  in  a  word,  that  the  whole  exquisite  mechanism  of 
cartilages,  ligaments,  and  muscles,  has  for  its  object  the  production 
of  a  sufficient  pressure  in  the  blast  of  air  driven  through  the  wind- 
pipe by  an  expiratory  act,  and  of  a  suitable  tension  in  the  vibrating 
cords.  An  approximation  of  the  cords,  a  narrowing  of  the  glottis, 
is  essential  to  the  production  of  voice;  with  a  widely-opened  glottis 
the  air  escapes  too  easily,  and  the  necessary  pressure  cannot  be 
attained.  The  pressure  in  the  windpipe  was  found  in  a  woman 
with  a  tracheal  fistula  to  be  about  12  mm.  of  mercury  for  a  note  of 
medium  height,  about  15  mm.  for  a  high  note,  and  about  72  mm. 
for  the  highest  possible  note.  The  period  of  vibration  of  structures 
like  the  vocal  cords  depends  on  their  length,  thickness,  density  and 
tension ;  the  shorter,  thinner,  more  dense  and  less  tense  a  stretched 
string  is,  the  greater  is  the  vibration  frequency,  the  higher  the  note. 
In  the  child  the  cords  are  short  (6  to  8  mm.),  in  woman  longer 
(10  to  12  mm.  when  slack,  13  to  15  mm.  when  stretched),  in  man 
longest  of  all  (14  to  18  mm.  in  the  relaxed,  and  18  to  22  mm.  in  the 
stretched  position) ;  and  the  lower  limit  of  the  voice  is  fixed  by  the 
maximum  length  of  the  relaxed  cords.  A  boy  or  a  woman  cannot 
utter  a  deep  bass  note,  because  their  vocal  cords  are  relatively 
short,  and  do  not  vibrate  with  sufficient  slowness.  It  is  true  that 
by  the  action  of  the  crico-thyroid  muscle  the  cords  can  be  length- 
ened, and  that  the  maximum  length  in  a  woman  approaches  or 
exceeds  the  minimum  length  in  a  man.  But  the  lengthening  of  the 
vocal  cords  in  one  and  the  same  individual  is  always  accompanied 
by  other  changes — increase  of  tension,  decrease  of  breadth  and 
thickness — which  tell  upon  the  vibration  frequency  in  the  opposite 
way,  and  more  than  compensate  the  effect  of  the  increase  of  length, 
so  that  for  high  notes  the  cords  are  longer  than  for  low.  The  con- 
traction of  the  thyro-arytenoid  muscle  is  a  more  influential  factor 
in  altering  the  tension  of  the  cords  than  the  contraction  of  the  crico- 
thyroid. It  is  probable  that,  when  the  highest  notes  are  uttered, 
only  the  anterior  portions  of  the  cords  are  free  to  vibrate,  their 
posterior  portions  being  damped  by  the  approximation  of  the  vocal 
processes  of  the  arytenoid  cartilages  by  the    contraction  of  the 


304  VOICE  AND  SPEECH 

lateral  crico-arytenoid  and  transverse  arytenoid  muscles.  The 
range  of  an  ordinary  voice  is  2  octaves;  by  training  2^  octaves  can 
be  reached;  but  in  exceptional  cases  a  range  of  3,  and  even  3^, 
octaves  (as  in  the  celebrated  singer  CataUni)  has  been  known. 

The  development  of  the  voice  in  children  is  of  great  interest.  At 
the  age  of  six  years  the  boy's  voice  has  a  rather  narrower  range  than 
the  girl's  in  both  directions.  The  boy's  voice  reaches  its  full  height 
in  the  twelfth  and  its  full  depth  in  the  thirteenth  year,  when  the  range 
is  almost  3  octaves,  its  upper  limit  being  a  semitone  higher  than  the 
girl's,  but  its  lower  limit  a  whole  tone  deeper.  When  the  voice  '  breaks  ' 
in  boys  at  the  age  of  puberty  it  falls  about  an  octave.  The  control  of 
the  vocal  organs  becomes  so  incomplete  that  only  in  one-fourth  of  the 
cases  can  notes  of  sufficient  steadiness  to  be  used  in  music  be  produced. 
The  vocal  cords,  as  may  be  seen  with  the  laryngoscope,  are  frequently, 
though  not  always,  congested. 

The  pitch  of  a  note,  while  it  depends  chiefly,  as  has  been  said,  on 
the  tension  of  the  vocal  cords,  rises  and  falls  somewhat  with  the 
strength  of  the  expiratory  blast ;  the  highest  notes  are  only  reached 
with  a  strong  expiratory  effort.  The  intensity  of  all  vocal  sounds 
is  determined  by  the  strength  of  the  blast,  for  the  ampHtude  of 
vibration  of  the  cords  is  proportional  to  this.  Besides  pitch  and 
intensity,  the  ear  can  still  distinguish  the  quality  or  timbre,  of  sounds; 
and  the  explanation  is  as  follows:  Two  simple  tones  of  the  same 
pitch  and  intensity,  that  is,  the  sounds  caused  by  two  series  of  air- 
waves of  the  same  period  and  ampUtude — of  the  same  frequency 
and  height,  to  use  less  technical  terms — would  appear  absolutely 
identical  to  the  sense  of  hearing;  just  as  the  aerial  disturbances  on 
which  they  depend  would  be  absolutely  alike  to  any  physical  test 
that  could  be  applied.  But  no  musical  instrument  ever  produces 
sound-waves  of  one  definite  period,  and  one  only;  and  the  same  is 
true  of  the  voice.  When  a  stretched  string  is  displaced  in  any  way 
from  its  position  of  rest,  it  is  set  into  vibration;  and  not  only  does 
the  string  vibrate  as  a  whole,  but  portions  of  it  vibrate  independently 
and  give  out  separate  tones.  The  tone  corresponding  to  the  vibra- 
tion period  of  the  whole  string  is  the  lowest  of  all.  It  is  also  the 
loudest,  for  it  is  more  difficult  to  set  up  quick  than  slow  vibrations. 
The  ear  therefore  picks  it  out  from  all  the  rest;  and  the  pitch  of  the 
compouad  note  is  taken  to  be  the  pitch  of  this,  its  fundamental 
tone.  The  others  are  called  partial  or  overtones,  or  harmonics  of 
the  fundamental  tone,  their  vibration  frequency  being  twice,  three 
times,  four  times,  etc.,  that  of  the  latter.  Now,  the  fundamental 
tone  of  a  compound  note  or  clang  produced  by  two  musical  instru- 
ments may  be  the  same,  while  the  number,  period,  and  intensity 
of  the  harmonics  are  different;  and  this  difference  the  ear  recognizes 
as  a  difference  of  timbre  or  quality.  The  timbre  of  the  voice  de- 
pends for  the  most  part  on  partial  tones  produced  or  intensified  in 
the  upper  resonance  chambers. 


VOICE 


305 


A  great  deal  of  our  knowledge  as  to  the  mode  and  mechanism  of 
the  production  of  voice  has  been  acquired  by  means  of  the  laryngo- 
scope (Fig.  143).  This  consists  of  a  small  plane  mirror  mounted  on 
a  handle,  which  is  held  at  the  back  of  the  mouth  in  such  a  position 
that  a  beam  of  light,  reflected  from  a  larger  concave  mirror  fastened 
on  the  forehead  of  the  observer,  is  thrown  into  the  larynx  of  the 
patient.  The  observer  looks  through  a  hole  in  the  centre  of  the 
large  mirror;  and  an  image  of  the  interior  of  the  larynx  is  seen  in 
the  small  mirror,  in  which  the  parts  that  are  anterior  appear  as 
posterior,  the  arytenoid  cartilages  in  front,  the  thyroid  behind,  and 
the  vocal  cords  stretching  between.  The  small  mirror  is  warmed  to 
body-temperature  before  being  introduced,  so  as  to  prevent  the 
condensation  of  moisture  on  it.     The  tendency  to  retch,  which  is 


Concave  Mirror 


Larynx, 


Fig.  143. — Diagram  of  Lairyngoscope. 

caused  by  contact  of  the  instrument  with  the  soft  palate,  may  be 
removed  or  lessened  by  the  application  of  a  solution  of  cocaine. 

Examined  with  the  laryngoscope  during  quiet  respiration,  the 
glottis  is  seen  to  be  moderately,  though  not  widely,  open,  and  the 
vocal  cords  almost  motionless.  Although  the  portion  between  the 
arytenoid  cartilages  has  received  the  name  of  glottis  respiratoria,  in 
contradistinction  to  the  glottis  vocalis  between  the  vocal  cords,  the 
rima  in  its  whole  extent  from  front  to  back  is  really  concerned  in 
the  respiratory  act.  In  deep  expiration  the  vocal  cords  come  nearer 
to  the  middle  line,  and  the  glottis  is  narrowed;  in  deep  inspiration 
they  are  widely  separated,  and  the  rings  of  the  trachea,  and  even 
its  bifurcation,  may  be  disclosed  to  view.  When  a  sound  is  produced 
— a  note  sung,  for  example — the  cords  are  approximated  (Figs.  144 
and  145) ;  and  with  a  high  note  more  than  with  a  low. 


3o6 


VOICE  AND  SPEECH 


The  essential  difference  between  the  production  of  notes  in  the  lower 
register,  or  chest  voice,  and  in  the  higher  register,  or  falsetto,  has  been 
much  debated.  The  lowest  notes  which  can  be  uttered  by  any  given 
voice  are  chest  notes,  the  highest  are  falsetto  notes;  but  there  is  a  de- 
batable land  common  to  both  registers,  and  medium  notes  can  be  sung 
eith-^r  from  the  chest  or  from  the  head.  Chest  notes  impart  a  vibration 
or  fremitus  to  the  thoracic  walls,  from  the  resonance  of  the  lower  air- 
chambers,  the  trachea  and  bronchi;  and  this  can  be  distinctly  felt  by 
the  hand.  In  head  notes  or  falsetto  the  resonance  is  chiefly  in  the 
upper  cavities,  the  pharynx,  mouth,  and  nose.  As  to  the  mechanical 
conditions  in  the  larynx,  there  is  a  pretty  general  agreement  that  during 
the  production  of  falsetto  notes  the  vocal  cords  are  less  closely  approxi- 
mated than  in  the  sounding  of  chest  notes.  The  escape  of  air  is  conse- 
quently more  rapid  in  the  head  voice,  and  a  falsetto  note  cannot  be 
maintained  so  long  as  a  note  sung  from  the  chest.  But  it  is  only  the 
anterior  part  of  the  rima  glottidis  that  is  wider  in  the  falsetto  voice ; 
the  whole  of  the  glottis  respiratoria,  and  even  the  posterior  portion  of 
the  glottis  vocalis,  are  closed  during  the  emission  of  falsetto  notes. 


Fig.  144.  —  Position  of  the 
Glottis  preliminary  to  the 
Utterance  of  Sound,  rs,  false 
vocal  cord ;  ri,  true  vocal 
cord;  ar,  arytenoid  cartilage; 
b,  pad  of  the  epiglottis. 


Fig.  145. — Position  of  Open  Glottis. 
I,  tongue;  e,  epiglottis;  ae,  ary- 
epiglottidean  fold;  c,  cartilage  of 
Wrisberg;  ar,  arytenoid  cartilage; 
o,  glottis;  V,  ventricle  of  Mor- 
gagni;  ti,  true  vocal  cord;  ts,  false 
vocal  cord. 


Ocrtel  has  stated,  and  the  statement  has  been  confirmed  by  others, 
that  the  free  edge  of  the  vocal  cord  alone  vibrates  in  the  falsetto  voice, 
one  or  more  nodes  or  motionless  lines  parallel  to  the  edge  being  formed 
by  the  contraction  of  the  internal  part  of  the  thyro-arytenoid  muscle, 
which  thus  acts  like  a  stop  upon  the  cord . 

Approximation  of  the  vocal  cords  may  take  place  in  certain 
acts  unconnected  with  the  production  of  voice.  Thus,  a  cough,  as 
has  already  been  mentioned,  is  initiated  by  closure  of  the  glottis. 
During  a  strong  muscular  effort,  too,  the  chink  of  the  glottis  is 
obliterated,  and  respiration  and  phonation  both  arrested.  The 
object  of  this  is  to  fix  the  thorax,  and  so  afford  points  of  support 
for  the  action  of  the  muscles  of  the  limbs  and  abdomen.  But  con- 
siderable efforts  can  be  made  even  by  persons  with  a  tracheal  fistula. 

Speech. — Ordinary  speech  is  articulated  voice — -voice  shaped  and 
fashioned  by  the  resonance  of  the  upper  air-cavities,  and  jointed 


SPEECH  307 

together  by  the  sounds  or  noises  to  which  the  varying  form  of  these 
cavities  gives  rise.  Here  we  come  upon  the  fundamental  distinction 
between  vowels  and  consonants.  Vowels  are  musical  sounds;  con- 
sonants are  not  musical  sounds,  but  noises — that  is  to  say,  they  are 
due  to  irregular  vibrations,  not  to  regularly  recurring  waves,  the 
frequency  of  which  the  ear  can  appreciate  as  a  definite  pitch.  This 
difference  of  character  corresponds  to  a  difference  of  origin:  the 
vowels  are  produced  by  the  vibrations  of  the  vocal  cords;  the  con- 
sonants are  due  to  the  rushing  of  the  expiratory  blast  through 
certain  constricted  portions  of  the  buccal  chamber,  where  ^  kind  of 
temporary  glottis  is  established  by  the  approximation  of  its  walls. 
One  of  these  '  positions  of  articulation  '  is  the  orifice  of  the  lips;  the 
consonants  formed  there,  such  as  p  and  b,  are  called  labials.  A 
second  articulation  position  is  between  the  anterior  part  of  the 
tongue  and  the  teeth  and  hard  palate.  Here  are  formed  the  dentals, 
t,  d,  etc.  The  ordinary  EngUsh  r,  and  the  r  of  the  Berwickshire  and 
East  Prussian  '  burr,'  also  arise  in  this  position  through  a  vibratory 
motion  of  the  point  of  the  tongue.  The  third  position  of  articula- 
tion is  the  narrow  strait  formed  between  the  posterior  portion  of  the 
arched  tongue  and  the  soft  palate.  To  the  consonants  arising  here 
the  name  of  gutturals  has  been  given.  They  include  k,  g,  the 
Scottish  ch,  and  the  uvular  German  r.  The  latter  is  produced  by 
a  vibration  of  the  uvula.  The  aspirated  h  is  a  noise  set  up  by  the 
air  rushing  through  a  moderately  wide  glottis,  and  some  have  there- 
fore included  the  glottis  as  a  fourth  articulation  position  for  con- 
sonants. Certain  sounds  like  n,  m,  and  ng,  when  final  (as  in  pen, 
dam,  ring),  although  produced  at  the  glottis,  are  intensified  by  the 
resonance  of  the  air  in  the  nose  and  pharynx,  and  are  sometimes 
spoken  of  as  nasal  consonants. 

As  we  have  said,  the  vowels  are  produced  by  vibrations  of  the 
vocal  cords,  but  to  what  they  owe  their  special  timbre  or  quality  has 
been  much  discussed.  According  to  the  view  with  which  Helm- 
holtz's  name  is  particularly  connected  this  is  due  to  the  reinforce- 
ment of  certain  overtones  by  the  resonating  cavities,  the  shape  and 
fundamental  tone  of  which  arc  different  for  each  vowel. 

When  a  vowel  is  whispered,  the  mouth  assumes  a  characteristic 
shape,  and  emits  the  fundamental  tone  proper  to  the  form  and  size 
of  the  particular  '  vowel-cavity,'  not  as  a  reinforcement  of  a  tone  set 
up  by  the  vibrations  of  the  vocal  cords,  but  in  response  to  the  rush  of 
air  through  the  cavity ;  just  as  a  bottle  of  given  shape  and  size  gives  out 
a  definite  note  when  the  air  which  it  contains  is  set  in  vibration,  by 
blowing  across  its  mouth.  A  whisper,  in  fact,  is  sp-^ech  without  voice; 
the  larynx  takes  scarcely  any  part  in  the  production  of  the  sound ;  the 
vocal  cords  remain  apart  and  comparatively  slack ;  and  the  expiratory 
blast  rushes  througli  without  setting  them  in  vibration. 

The  fundamental  tone  of  the  '  vowel-cavity  '  may  be  found  for  each 
vowel  by  placing  the  mouth  in  the  position  necessary  for  uttering  it, 
then  bringing  tuning-forks  of  dififerent  period  in  front  of  it,  and  noting 


3o8 


VOICE  AND  SPEECH 


which  of  them  sets  up  sympathetic  resonance  in  the  air  of  the  mouth, 
and  so  causes  its  sound  to  be  intensified.  The  fundamental  tone  is 
lowest  for  u  (as  in  lute) .  Next  comes  o  ;  then  a  (as  in  path) ;  then  a  (as 
in  fane) ;  then  i  ;  while  e  is  highest  of  all.  A  simple  illustration  of 
this  may  be  found  in  the  fact  that  when  the  vowels  are  whispered  in 
the  order  given,  the  pitch  rises.  When  m  or  o  is  sounded,  the  buccal 
cavity  has  the  form  of  a  widc-belUed  flask,  with  a  short  and  narrow  neck 
for  u,  a  still  shorter  but  wider  neck  for  o.  For  e  the  tongue  is  raised 
and  almost  in  contact  with  the  palate,  and  the  cavity  of  the  mouth 
is  shaped  like  a  flask  with  a  long  narrow  neck  and  a  very  short  belly. 
For  i  the  shape  is  similar,  but  the  neck  is  not  so  narrow.  For  a  (as  in 
path)  the  vowel-cavity  is  intermediate  in  form  between  that  of  ii  and  e, 
being  roughly  funnel-shaped,  and  the  mouth  is  rather  widely  opened. 
For  u  {oo)  the  resonating  cavity  is  made  as  long  as  possible,  the  larynx 
being  depressed  and  the  lips  protruded;  for  e  the  resonating  cavit\  is 
at  its  shortest,  the  larynx  being  raised  as  much  as  possible  and  the  lips 
retracted  (Figs.  146  to  148). 

According  to  Helmholtz,  all  that  the  resonating  cavity  does  is  to 
strengthen  certain  of  the  partials  or  overtones  of  the  laryngeal  note. 


Fig.  146. 


Fig.  147. 


Fig.  148. 


If  this  is  true,  the  partials  which  give  a  vowel-sound  the  timbre  by 
which  we  recognize  it  as  different  from  other  vowel-sounds  cannot 
preserve  the  same  numerical  relation  to  the  fundamental  tone  when 
the  pitch  of  the  latter  is  altered.  Suppose,  for  example,  that  a  given 
vowel  is  sounded  with  a  pitch  corresponding  to  100  vibrations  a  second, 
and  that  the  partial  which  is  particularly  strengthened  by  the  resonance 
of  the  mouth  cavity  is  the  fifth  overtone,  corresponding  to  600  vibra- 
tions. Then  when  the  same  vowel  is  sounded  with  a  pitch  of  200  vibra- 
tions, the  reinforced  partial  which  will  now  give  the  quality  to  the  sound 
will  still  correspond  to  600  vibrations  a  second,  since  this  is  the  rate 
which  most  easily  elicits  the  resonance,  but  it  will  not  now  be  the  fifth 
but  the  second  overtone. 

Universally  accepted  for  a  time,  the  Helmholtz  theory  has  been  in 
recent  years  assailed,  especially  by  Hcrinann,  who  bases  his  criticism 
on  microscopic  examination  of  curves  obtained  by  the  Edison  phono- 
graph, and  on  reproductions  of  such  records  obtained  by  photographing 
on  a  moving  drum  covered  with  sensitive  paper  a  beam  of  light  re- 
flected from  a  small  mirror  attached  to  a  system  of  levers  whose  move- 
ments follow  the  curves  faithfully  and  greatly  magnify  them.     Hermann 


SPEECH  309 

has  come  to  the  conclusion  that  the  mouth  does  not  act  as  a  mere 
resonator,  but  that  for  each  vowel,  in  addition  to  the  fundamental 
note  due  to  the  vibration  of  the  vocal  cords,  the  pitch  of  which  is,  of 
course,  variable,  one  or,  it  may  be,  two  other  notes  (formants,  as  he 
calls  them),  not  necessarily  harmonics  of  the  laryngeal  note,  but  separ- 
ated from  it  by  a  constant  or  nearly  constant  musical  interval,  are 
directly  produced  by  the  passage  of  the  regularly  interrupted  expiratory 
blast  through  the  mouth,  the  air  contained  in  that  cavity  being  for 
an  instant  set  into  vibration  at  each  interruption.  On  this  view  it 
is  the  musical  effect  produced  by  the  oscillation  or  continual  recurrence, 
in  short  series,  of  these  vibrations  which  gives  the  vowels  their  quality. 
The  fact  that  it  is  by  no  means  difficult  to  sing  (with  the  larynx)  and 
whistle  (with  the  mouth)  at  the  same  time,  shows  the  possibility  of 
Hermann's  view,  that  a  fixed  tone  can  be  generated  in  the  mouth  by 
the  intermittent  stream  of  air  issuing  from  between  the  vibrating  vocal 
cords,  just  as  a  tone  is  generated  in  a  pipe  by  blowing  into  or  over  it, 
and  his  records  do  show  continually  recurring  groups  of  vibrations  as 
his  theory  requires.  McKendrick  takes  up  a  middle  position,  believing 
that  both  theories  are  partially  true,  and  this  seems  to  be  the  best 
conclusion  whicli  can  at  present  be  arrived  at.  It  seems  clear,  at  any 
rate,  that  more  than  one  factor  is  concerned  in  the  timbre  of  the  vowel 
sounds. 

When  the  vowels  are  being  uttered,  the  soft  palate  closes  the 
entrance  to  the  nasal  chambers  completely,  as  may  be  shown  by 
holding  a  candle  in  front  of  the  nose,  or  trying  to  inject  water 
through  the  nares.  If  the  cavities  of  the  nose  are  not  completely 
blocked  off,  the  voice  assumes  a  nasal  character  in  pronouncing 
certain  of  the  vowels;  and  in  some  languages  this  is  the  ordinary 
and  correct  pronunciation. 

Many  animals  have  the  power  of  emitting  articulated  sounds;  a 
few  have  risen,  like  man,  to  the  dignity  of  sentences,  but  these  only 
by  imitation  of  the  human  voice.  Both  vowels  and  consonants  can 
be  distinguished  in  the  notes  of  birds,  the  vocal  powers  of  which 
are  in  general  higher  than  those  of  mammalian  animals.  The  latter, 
as  a  rule,  produce  only  vowels,  though  some  are  able  to  form  con- 
sonants too. 

The  nervous  mechanism  of  voice  and  speech  will  have  to  be 
again  considered  when  we  come  to  study  the  physiology  of  the  brain 
and  spinal  cord.  But  the  curious  physiological  antithesis  between 
the  functions  of  abduction  and  of  adduction  of  the  vocal  cords  may 
be  mentioned  here.  The  abductor  muscles  are  not  employed  in  the 
production  of  voice;  they  are  associated  with  the  less  speciaUzed, 
the  less  skilled  and  purposive  function  of  respiration.  The  adductor 
muscles  are  not  brought  into  action  in  respiration;  they  are  asso- 
ciated with  the  highly  specialized  function  of  speech.  Correspond- 
ing to  tliis  difference  of  function,  we  find  that  adduction  is  pre- 
ponderatingly  represented  in  the  cortex  of  the  brain,  abduction  in 
the  medulla  oblongata.  Stimulation  of  an  area  in  the  lower  part 
of  the  ascending  frontal  convolution,  near  the  fissure  of  Rolando,  in 
the  macaque  monkey,  causes  adduction  of  the  vocal  cords,  never 


5tO  VOICE  AND  SPEECH 

abduction.  In  the  cat,  however,  abduction  of  the  cords  may  also 
be  obtained  by  stimulation  of  the  cortex.  The  same  is  true  of  the 
dog,  but  only  when  the  peripheral  adductor  nerves  have  been 
divided.  Stimulation  of  the  medulla  oblongata  (accessory  nucleus) 
causes  abduction,  never  adduction.  The  skilled  adductor  function 
is,  therefore,  placed  under  control  of  the  cortex.  The  vitally  im- 
portant, but  more  mechanical,  abductor  function  is  governed  by 
the  medulla.  The  abductor  movements  are  more  likely  to  be 
affected  by  organic  disease,  the  adductor  movements  by  functional 
changes.  But  the  distinction  between  the  two  groups  of  muscles 
is  not  entirely  due  to  a  difference  of  central  connections,  since  by 
altering  the  strength  of  the  stimulus  and  the  external  conditions 
the  one  or  the  other  may  be  separately  excited  through  the  inferior 
larjmgeal  nerve.  Thus,  strong  stimulation  of  the  inferior  laryngeal 
causes  closure  of  the  glottis,  for  although  it  supplies  both  abductors 


Fig.  149. — Diagram  of  Vocal  Cords  in  Paralyses  of  the  Larynx,  a.  Paralysis  of  both 
inferior  laryngeal  nerves.  The  vocal  cords  have  taken  up  the  '  mean  '  position. 
b.  Paralysis  of  right  inferior  laryngeal  nerve.  An  attempt  is  being  made  to 
narrow  the  glottis  for  the  utterance  of  sound.  The  right  cord  remains  in  its 
"  mean  '  position,  c.  Paralysis  of  the  abductor  muscles  only,  on  both  sides.  The 
cords  are  approximated  beyond  the  '  mean '  position  by  the  action  of  the 
adductors. 

and  adductors,  the  latter,  as  the  stronger  muscles,  prevail.  With 
weak  stimulation,  and  in  young  animals,  the  abductors,  owing  to 
the  greater  excitability  of  the  neuro-muscular  apparatus,  carry  off 
the  victory,  and  the  glottis  is  opened  (Russell). 

When  the  nerve  is  cooled  the  abductors  give  way  before  the 
adductors.  The  same  is  true  when  it  is  allowed  to  become  dry. 
And  after  death  in  a  cholera  patient  it  was  observed  that  the  pos- 
terior crico-arytenoid,  an  abductor  muscle,  was  the  first  of  the 
intrinsic  laryngeal  muscles  to  lose  its  excitability.  Lesions  of  the 
medulla  oblongata  are  often  accompanied  by  marked  changes  in 
the  character  of  the  voice  and  the  power  of  articulation. 

Section  or  paralysis  of  the  superior  laryngeal  nerve  causes  the 
voice  to  become  hoarse,  and  renders  the  sounding  of  high  notes  an 
impossibility,  owing  to  the  want  of  power  to  make  the  vocal  cords 
tense.    Stimulation  of  the  vagus  within  the  skull  causes  contraction 


.SPEECH  311 

of  the  crico-thyroid  muscle  and  increased  tension  of  the  cords.  Sec- 
tion or  paralysis  of  the  inferior  laryngeal  nerves  leads  to  loss  of  voice 
or  aphonia,  and  dyspnoea  (Fig.  149).  Both  adductor  and  abductor 
muscles  are  paralyzed;  the  vocal  cords  assume  their  mean  position — 
the  position  they  have  in  the  dead  body — and  the  glottis  can  neither 
be  narrowed  to  allow  of  the  production  of  a  note,  nor  widened  during 
inspiration.  It  is  said,  however,  that  young  animals,  in  which  the 
structures  around  the  glottis  are  more  yielding  than  in  adults,  can 
still  utter  shrill  cries  after  section  of  the  inferior  laryngeals,  the 
contraction  of  the  crico-thyroid  muscle  alone  being  able,  while  in- 
creasing the  tension  of  the  cords,  to  draw  them  together. 

Interference  with  the  connections  on  one  side  between  the  higher 
cerebral  centres  and  the  medulla  oblongata,  as  by  rupture  of  an 
artery  and  effusion  of  blood  into  the  posterior  portion  of  the  internal 
capsule  (giving  rise  to  hemiplegia,  or  paralysis  of  the  opposite  side 
of  the  body),  is  not  followed  by  loss  of  voice;  the  laryngeal  muscles 
on  both  sides  are  still  able  to  act. 


CHAPTER   VI 
DIGESTION 

In  the  last  chapter  we  have  described  the  manner  in  which  the 
interchange  of  gases  between  the  tissues  and  the  air  is  carried  out. 
We  have  now  to  consider  the  digestion  and  absorption  of  the  sohd 
and  hquid  food,  its  further  fate  in  relation  to  the  chemical  changes 
or  metabohsm  of  the  tissues,  and  finally  the  excretion  of  the  waste 
products  by  other  channels  than  the  lung. 

Logically,  we  ought  to  take  metabohsm  after  absorption  and 
before  excretion,  tracing  the  food  through  all  its  vicissitudes  from  the 
moment  when  it  enters  the  blood  or  lymph  till  it  is  cast  out  as  useless 
matter  by  the  various  excretory  organs.  Unfortunately,  however, 
many  of  the  intermediate  steps  of  the  process  are  as  yet  hidden  from 
us ;  we  know  best  the  beginning  and  the  end.  We  can  follow  the  food 
from  the  time  it  enters  the  ahmentary  canal  till  it  is  taken  up  by  the 
tissues  of  absorption;  and  we  have  really  a  fair  knowledge  of  this 
part  of  its  course.  We  can  collect  the  end-products  as  they  escape 
in  the  urine,  or  in  the  breath,  or  in  the  sweat ;  and  our  knowledge  of 
them  and  of  the  manner  in  which  they  are  excreted  is  considerable. 
But  of  the  wonderful  pathway  by  which  the  dead  molecules  of  the 
food  mount  up  into  life,  and  then  descend  again  into  death,  we 
catch  only  a  glimpse  here  and  there.  Only  the  introduction  and 
the  conclusion  of  the  story  of  metabolism  are  at  present  in  our 
possession  in  fairly  continuous  and  legible  form.  We  will  read  these 
before  we  try  to  decipher  the  handful  of  torn  leaves  which  represents 
the  rest. 

Section  I. — Preliminary  Anatomical  and  Chemical  Data. 

Comparative. — In  the  lowest  kinds  of  animals,  such  as  the  anioeba, 
there  is  neither  mouth,  nor  alimentary  canal,  nor  anus:  the  food, 
wrapped  round  by  pseudopodia,  is  taken  in  at  any  part  of  the  animal 
with  which  it  happens  to  come  in  contact.  A  vacuole  is  formed  around 
it.  Acid  is  secreted  into  the  vacuole,  the  food  is  digested  within  the 
cell-substance,  and  the  part  of  it  which  is  useless  for  nutrition  is  cast 
out  again  at  any  part  of  the  surface. 

Coming  a  little  higher,  we  find  in  the  Ccelenterates  a  mouth  and 
alimentary  tube,   which  opens  into  the  body-cavity,  where  a  certain 

312 


PRELIMINARY  ANATOMICAL  AND  CHEMICAL  DATA        313 

amount  of  digestion  seems  to  take  place,  and  from  which  tiie  food  is 
absorbed  either  through  the  cells  of  the  endoderm,  or,  as  in  Medusa, 
by  means  of  fine  canals,  which  radiate  from  the  body-cavity  into  its 
walls,  and  form  part  of  the  so-called  gastro-vascular  system.  In  the 
Echinodermata  we  have  a  further  development,  a  complete  alimentary 
canal  with  mouth  and  anus,  and  entirely  shut  off  from  the  body-cavity. 
In  many  Arthropods  it  is  possible  already  to  distinguish  parts  corre- 
sponding to  the  stomach,  and  the  small  and  large  intestines  of  higher 
form.s,  the  digestive  glands  being  represented  by  organs  which  in  some 
groups  seem  to  be  homologous  with  the  liver,  and  in  others  with  the 
salivary'  glands  of  the  higher  Vertebrates.  A  few  Molluscs  seem  in 
addition  to  possess  a  pancreas. 

Among  Vertebrates  fishes  have  the  simplest,  and  birds  and  mammals 
the  most  complicated,  alimentary  system.  In  the  lowest  fishes  the 
stomach  is  only  indicated  by  a  slight  widening  of  the  anterior  part  of 
the  digestive  tube.  In  water-living  Vertebrates  there  are  no  salivary 
glands.  In  birds  the  oesophagus  is  generally  dilated  to  form  a  crop, 
from  which  the  food  passes  into  a  stomach  consisting  of  two  parts, 
one  pre-eminently  glandular  (proventriculus),  the  other  pre-eminently 
muscular  (ventriculus).  Among  mammals  a  twofold  division  of  the 
stomach  is  distinctly  indicated  in  rodents  and  cetaceae,  but  tlus  organ 
reaches  its  greatest  complexity  m  ruminants,  which  possess  no  fewer 
than  four  gastric  pouches.  The  differentiation  of  the  intestine  into 
small  and  large  intestine  and  rectum  is  more  distinct,  both  anatomically 
and  functionally,  in  mammals  than  in  lower  forms ;  but  there  are  marked 
differences  between  the  various  mammalian  groups  both  in  the  relative 
size  of  the  several  parts  of  the  digestive  tube,  and  in  the  proportion 
between  the  total  length  of  the  alimentary  canal  and  the  length  of  the 
body.  In  general,  the  canal  is  longest  in  herbivora,  shortest  in  carni- 
vora.  Thus,  the  ratio  between  length  of  body  and  length  of  intestine 
is  in  the  cat  i  :  4,  dog  i  :  6,  man  i  :  5  or  6,  horse  1:12,  cow  i  :  20,  sheep 
1:27.  The  relative  capacity  of  the  stomach,  small  intestine,  and  large 
intestine,  is  in  the  dog  6:2:1-5,  in  the  horse  i  :  3'5  :  7,  in  the  cow 
7:2:1.  The  area  of  the  mucous  surface  of  the  alimentary  canal  is 
very  considerable,  in  the  dog  more  than  half  that  of  the  skin,  the 
surface  of  the  small  mtestine  being  three  times  that  of  the  stomach 
and  four  times  that  of  the  large  intestine.  In  the  horse  the  mucous 
surface  has  twice  the  area  of  the  skin. 

Anatomy  of  the  Alimentary  Canal  in  Man. — The  alimentary  canal 
is  a  muscular  tube,  which,  beginning  at  the  mouth,  runs  under  the 
various  names  of  pharynx,  oesophagus,  stomach,  small  intestine,  large 
intestine,  and  rectum,  till  it  ends  at  the  anus.  Its  walls  are  largely 
composed  of  muscular  fibres;  its  lumen  is  clad  with  epithelium,  and 
into  it  open  the  ducts  of  glands,  which,  morphologically  speaking,  are 
involutions  or  diverticula  formed  in  its  course.  In  virtue  of  its  muscular 
fibres  it  is  a  contractile  tube;  in  virtue  ot  its  epithelial  lining  and  its 
special  glands  it  is  a  secreting  tube ;  in  virtue  of  both  it  is  fitted  to  per- 
form those  mechanical  and  chemical  actions  upon  the  food  which 
are  necessary  for  digestion.  Its  inner  surface  is  in  most  parts  richly 
supplied  witli  bloodvessels,  and  in  special  regions  beset  with  peculiarly- 
arranged  l>Tnphatics;  by  both  of  these  channels  the  alimentary  tube 
performs  its  function  of  absorption.  From  the  beginning  of  the  oeso- 
phagus to  the  end  of  the  rectum  the  muscular  wall  consists,  broadly 
speaking,  of  an  outer  coat  of  longitudinally-arranged  fibres,  and  a 
thicker  inner  coat  of  fibres  running  circularly  or  transversely  around 
the  tube.  Between  the  layers  lies  a  plexus  of  non-medullated  nerves 
and  nerve-cells  (Auerbach's  plexus).     In  the  stomach  the  longitudinal 


314  DIGESTION 

fibres  are  found  only  on  the  two  curvatures,  and  a  third  incomplete 
coat  of  obUque  fibres  makes  its  appearance  internal  to  the  circular 
layer.  In  the  large  intestine,  again,  the  longitudinal  fibres  are  chiefly 
collected  into  three  isolated  strands.  In  the  pharynx  the  typical 
arrangement  is  departed  from,  inasmuch  as  there  is  no  regular  longi- 
tudinal layer;  but  the  three  constrictor  muscles  represent  to  a  certain 
extent  the  great  circular  coat.  The  muscles  of  the  mouth  and  of  the 
pharynx  are  of  the  striped  variety.  So  is  the  muscle  of  the  upper  half 
of  the  oesophagus  in  man  and  the  cat,  and  of  the  whole  oesophagus 
in  the  dog  and  the  rabbit.  In  the  rest  of  the  alimentary  canal  the 
muscle  is  smooth,  except  at  the  very  end,  where  the  external  sphincter 
of  the  anus  is  striped.  In  certain  situations  the  circular  coat  is  de- 
veloped into  a  regular  anatomical  sphincter,  a  definite  muscular  ring, 
whose  function  it  is  to  shut  one  part  of  the  tube  off  from  another 
(sphincter  pylori,  ileo-colic  sphincter),  or  to  help  to  close  the  external 
opening  of  the  tube  (internal  sphincter  of  anus).  Elsewhere  a  tonic 
contraction  of  a  portion  of  the  circular  coat,  not  anatomically  de- 
veloped beyond  the  rest,  creates  a  functional  sphincter  (cardiac  sphincter 
of  stomach). 

Throughout  the  greater  part  of  the  digestive  tract  the  peritoneum 
forms  a  thin  serous  layer,  external  to  the  muscular  coat.  Internally 
the  muscular  coat  is  separated  from  the  mucous  membrane,  the  lining 
of  the  canal,  by  some  loose  areolar  tissue  containing  bloodvessels, 
lymphatics,  and  nerves  (Meissner's  plexus),  and  called  the  submucous 
coat.  Between  the  mucous  and  submucous  layers,  but  belonging  to 
the  former,  in  the  whole  canal  below  the  beginning  of  the  oesophagus, 
is  a  thin  coat  of  smooth  muscular  fibres,  the  muscularis  mucosae,  con- 
sisting in  some  parts,  e.g.,  in  the  stomach,  of  two,  or  even  three, 
layers.  Between  this  and  the  lumen  of  the  canal  lie  the  ducts  and 
alveoli  of  glands,  surrounded  by  bloodvessels  and  embedded  in  adenoid 
or  lymphoid  tissue,  which  in  particular  regions  is  collected  into  well- 
defined  masses  (solitary  follicles,  Peyer's  patches,  tonsils),  extending, 
it  may  be,  into  the  submucous  tissue.  In  the  mouth,  pharynx,  and 
oesophagus,  the  glands  lie  in  the  submucosa,  as  do  the  glands  of  Brunner 
in  the  duodenum;  everywhere  else  they  are  confined  to  the  mucous 
membrane  proper.  Between  the  openings  of  the  glands  the  mucous 
membrane  is  lined  with  a  single  layer  of  columnar  epithelial  cells,  some- 
times (in  the  small  intestine)  arranged  along  the  sides  of  tiny  projec- 
tions or  villi.  When  the  intestine  is  contracted  the  villi  are  long  and 
cylindrical  in  shape,  when  it  is  relaxed  or  distended  they  are  flat  and 
conical.  At  the  ends  of  the  alimentary  canal,  viz.,  in  the  mouth, 
pharynx,  and  oesophagus,  and  at  the  anus,  the  epithelium  is 'stratified 
squamous,  and  not  columnar. 

The  purpose  of  food  is  to  supply  the  waste  of  the  tissues,  to 
replenish  the  stores  of  material  from  the  oxidation  of  which  the 
energy  required  for  the  running  of  the  bodily  machine  is  derived,' 
and  thus  to  maintain  the  normal  composition  of  the  body.  In  the 
body  we  find  a  multitude  of  substances  marked  off  from  each  other, 
some  by  the  sharpest  chemical  differences,  others  by  characters 
much  less  distinct,  but  falling  upon  the  whole  into  the  few  fairly 
definite  groups  already  described  (p.  i). 

Now,  although  it  is  by  no  means  necessary  that  a  substance  in 
the  body  belonging  to  one  of  these  great  groups  should  be  derived 
from  a  substance  of  the  same  group  in  the  food,  it  has  been  found 


PRELIMINARY  ANATOMICAL  AND  CHEMICAL  DATA  315 

that  upon  the  whole  no  diet  is  sufficient  for  man  unless  it  contains 
representatives  of  all;  a  proper  diet  must  include  proteins,  carbo- 
hydrates, fats,  inorganic  salts,  and  water.  These  proximate  prin- 
ciples have  to  be  obtained  from  the  raw  material  of  the  foodstuffs — 
that  is,  as  regards  the  first  three  groups,  which  can  alone  yield 
energy  in  the  body,  from  the  tissues  and  juices  of  other  living  things, 
plants  or  animals;  it  is  the  business  of  digestion  to  sift  them  out  and 
to  prepare  them  for  absorption.  This  preparation  is  partly  mechan- 
ical, partly  chemical. 

The  water  and  salts  and  some  carbo-hydrates,  such  as  dextrose, 
are  ready  for  absorption  without  change.  Fats  are  split  into 
glycerin  and  fatty  acids  before  absorption.  Indiffusible  colloidal 
carbo-hydrates,  like  starch  and  dextrin,  are  changed  into  diffusible 
and  readily  soluble  sugars,  and  the  natural  proteins  into  diffusible 
peptones,  and  eventually  into  much  simpler  decomposition  products. 
These  changes  are  obviously  favourable  to  absorption.  But  this  is 
not  their  whole  significance.  For  disaccharides,  such  as  cane-sugar, 
maltose,  or  lactose,  although  easily  soluble  in  the  contents  of  the 
gut,  and  in  themselves  perfectly  capable  of  being  absorbed  without 
change,  are,  unless  present  in  unusually  large  amount,  all  converted 
into  monosaccharides,  such  as  dextrose,  levulose,  or  galactose,  either 
in  the  lumen  or  in  the  wall  of  the  alimentary  tube.  The  reason  is 
that  the  disaccharides  are  unsuitable  as  pabulum  for  the  cells. 
Digestion  is  not  only  a  preparation  of  the  food  for  absorption  by 
the  gut,  but  for  assimilation  by  the  tissues  after  absorption.  An 
equally  important  instance  of  this  double  function  is  seen  in  the 
digestion  of  proteins.  The  complete  shattering  of  the  protein  mole- 
cule into  amino-acids  and  the  other  groups  yielded  by  its  decom- 
position (p.  354)  is  required,  in  the  case  of  that  portion  of  the  protein 
which  goes  to  build  up  the  tissues,  because  of  the  high  degree  of 
specificity  of  the  tissue  proteins.  The  myosinogen  of  beef  cannot 
be  cobbled  into  the  myosinogen  of  human  muscle,  still  less  we  may 
suppose  into  the  serum-albumin  of  human  blood.  It  is  necessary 
that  the  food  protein  should  be  completely  '  wrecked  '  in  digestion 
so  that  protein  which  is  to  take  its  place  in  protoplasm  may  be  built 
exactly  to  order  from  the  bricks.  A  satisfactory  '  fit  '  cannot  be 
obtained  with  ready-made  protein.  Mechanical  division  of  the  food 
is  an  important  aid  to  the  chemical  action  of  the  digestive  juices.  We 
shall  see  that  this  mechanical  division  forms  a  great  part  of  the  work 
of  the  stomach,  but  it  is  normally  begun  in  the  mouth,  and  it  is  of 
consequence  that  this  preliminary  stage  should  be  properly  performed. 

Section  II. — The  Mechanical  Phenomena  of  Digestion. 

Mastication. — It  is  among  the  mammaha  that  regular  mastication 
of  the  food  first  makes  its  appearance  as  an  important  aid  to  diges- 
tion.    The  amphibian  bolts  its  fly,  the  bird  its  grain,  and  the  fish 


3i6  DIGESTION 

its  brother,  without  the  ceremony  of  chewing.  In  ruminating 
mammals  we  see  mastication  carried  to  its  highest  point ;  the  teeth 
work  all  day  long,  and  most  of  them  are  specially  adapted  for 
grinding  the  food.  The  carnivora  spend  but  a  short  time  in  masti- 
cation; their  teeth  are  in  general  adapted  rather  for  tearing  and 
cutting  than  for  grinding.  Where  the  diet  is  partly  animal  and 
partly  vegetable,  as  in  man,  the  teeth  are  fitted  for  all  kinds  of  work ; 
and  the  process  of  mastication  is  in  general  neither  so  long  as  in  the 
purely  vegetable  feeders,  nor  so  short  as  in  the  carnivora. 

In  man  there  are  two  sets  of  teeth :  the  temporary  or  milk  teeth, 
and  the  permanent  teeth.  The  milk  teeth  are  twenty  in  number, 
and  consist  on  each  side  of  four  incisors  or  cutting-teeth,  two 
canines  or  tearing-teeth,  and  four  molars  or  grinding-teeth.  The 
central  incisors  emerge  at  the  seventh  month  from  birth,  the  other 
incisors  at  the  ninth  month,  the  canines  at  the  eighteenth,  and  the 
molars  at  the  twelfth  and  twenty-fourth  month  respectively. 
Each  tooth  in  the  lower  jaw  appears  a  Httle  before  the  corresponding 
one  in  the  upper  jaw.  Each  of  the  milk  teeth  is  in  course  of  time 
replaced  by  a  permanent  tooth,  and  in  addition  the  vacant  portion 
of  the  gums  behind  the  milk  set  is  now  filled  up  by  twelve  teeth, 
six  on  each  side,  three  above  and  three  below.  These  twelve  are 
the  permanent  molars;  they  raise  the  number  of  the  permanent 
teeth  to  thirty-two.  The  permanent  teeth  which  occupy  the 
position  of  the  milk  molars  now  receive  the  name  of  premolars. 
The  first  tooth  of  the  permanent  set  (the  first  true  molar)  appears 
at  the  age  of  6|  years;  the  last  molar,  or  wisdom-tooth,  does  not 
emerge  till  the  seventeenth  to  the  twenty-fifth  year. 

In  mastication  the  lower  jaw  is  moved  up  and  down,  so  as  to 
alternately  separate  and  approximate  the  two  rows  of  teeth.  It  has 
also  a  certain  amount  of  movement  from  side  to  side,  and  from  front 
to  back.  The  masseter,  temporal  and  internal  pterygoid  muscles 
raise,  and  the  digastric,  with  the  assistance  of  the  mylo-  and  genio- 
hyoid, depresses,  the  lower  jaw,  but  its  downward  movement  is 
mainly  a  passive  one.  The  external  pterygoids  pull  it  forward 
when  both  contract,  forward  and  to  one  side  when  only  one  con- 
tracts. The  lower  fibres  of  the  temporal  muscle  retract  the  jaw. 
The  buccinator  and  orbicularis  oris  muscles  prevent  the  food  from 
passing  between  the  teeth  and  the  cheeks  and  lips.  The  tongue 
keeps  the  fbod  in  motion,  works  it  up  with  the  saliva,  and  finally 
gathers  it  into  a  bolus  ready  for  deglutition. 

Deglutition.— This  act  consists  of  a  voluntary  and  an  involun- 
tary stage.  Just  before  the  beginning  of  the  voluntary  stage 
mastication  is  suspended,  and  a  slight  contraction  of  the  dia- 
phragm generally  takes  place.  The  anterior  part  of  the  tongue 
is  suddenly  elevated  and  pressed  against  the  hard  palate,  and  the 
elevation  travels  back  from  the  tip  towards  the  root,  as  the  mylo- 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION  31? 

hyoid  muscles  in  the  floor  of  the  mouth  contract  sharply  so  as  to 
thrust  the  bolus  through  the  isthmus  of  the  fauces.  As  soon  as  this 
has  happened,  and  the  food  lias  reached  the  posterior  portion  of  the 
tongue,  it  has  passed  beyond  the  control  of  the  will,  and  the  second 
or  involuntary  stage  of  the  process  begins. 

This  stage  may  be  divided  into  two  parts:  (i)  Pharyngeal, 
(2)  oesophageal — both  being  reflex  acts.  During  the  first  the  food 
has  to  pass  through  the  pharynx,  the  upper  portion  of  which  forms 
a  part  of  the  respiratory  tract,  and  is  in  free  communication  with 
the  larynx  during  ordinary  breathing.  'It  is  therefore  necessary 
that  respiration  should  be  interrupted  and  the  larynx  closed  while 
the  food  is  being  moved  through  the  pharynx.  But  that  the  inter- 
ruption may  be  short,  the  food  must  be  rapidly  passed  over  this 
perilous  portion  of  its  descent.  The  main  propelling  force  under 
which  the  bolus  is  shot  through  the  back  of  the  pharynx  is  derived 
from  the  contraction  of  the  mylo-hyoid  muscles  already  mentioned, 
assisted  to  some  extent  by  the  stylo-  and  palato-glossi ;  and  that 
none  of  the  purchase  may  be  lost,  the  pharyngeal  cavity  is  cut  off 
from  the  nose  and  mouth  as  soon  as  the  bolus  has  entered  it.  The 
soft  palate  is  raised  by  the  levator  palati  and  palato-pharyngei 
muscles;  at  the  same  time  the  upper  part  of  the  pharynx,  narrowed 
by  the  contraction  of  the  superior  constrictor,  comes  forward  to 
meet  the  soft  palate,  closes  in  upon  it,  and  so  prevents  the  food 
from  passing  into  the  nasal  cavities.  The  pharynx  is  cut  off  from 
the  mouth  by  the  closure  of  the  fauces  through  the  contraction  of 
the  palato-pharyngeal  muscles  which  lie  in  their  posterior  pillars. 
The  upper  free  end  of  the  epiglottis  (the  so-called  pharyngeal  part) 
aids  the  back  of  the  tongue  in  completing  a  movable  partition  across 
the  pharynx,  which  keeps  close  to  the  bolus  as  it  passes  down 
between  the  posterior  surface  of  the  epiglottis  and  the  posterior 
wall  of  the  pharynx.  Almost  immediately  after  the  contraction 
of  the  mylo-hyoids  the  larynx  is  pulled  upwards  and  forwards  by 
the  contraction  of  the  thyro-hyoid  muscle,  and  the  elevation  of  the 
hyoid  bone  by  the  muscles  which  connect  it  to  the  lower  jaw. 
The  base  of  the  tongue  is  simultaneously  drawn  backwards  by  the 
stylo-  and  palato-glossus.  The  lower  or  laryngeal  portion  of  the 
epiglottis  is  thus  caused  to  come  into  contact  with  the  upper  orifice 
of  the  larynx,  occluding  it  completely,  but  the  pharyngeal  portion 
projects  beyond  the  larynx,  and  takes  no  share  in  its  closure 
(Eykman).  The  glottis  is  closed  by  the  approximation  of  the  vocal 
cords  and  the  arytenoid  cartilages.  The  epiglottis,  however,  is  not 
absolutely  indispensable  for  closing  the  lar^Tix,  since  swallowing 
proceeds  in  the  ordinary  way  when  it  is  absent.  The  morsel  of 
food,  grasped  by  the  middle  and  lower  constrictors  as  it  leaves  the 
back  of  the  tongue,  passes  rapidly  and  safely  over  the  closed  larynx, 
the  process  being  accelerated  by  the  pulling  up  of  the  lower  portion 


3i8  DIGESTION 

of  the  phar5mx  over  the  bolus  by  the  action  of  the  palato-  and  stylo- 
pharyngei. 

The  second  or  oesophageal  portion  of  the  involuntary  stage  is 
a  more  leisurely  performance.  The  bolus  is  carried  along  by  a 
peculiar  '  peristaltic '  contraction  of  the  muscular  wall  of  the 
oesophagus,  which  travels  down  as  a  wave,  constricting  the  tube 
and  pushing  the  food  before  it.  In  front  of  the  constricting  wave 
moves  a  wave  of  inhibition,  so  that  the  part  of  the  oesophagus  into 
which  the  bolus  is  about  to  pass  is  always  relaxed,  while  the  part 
behind  it  is  contracted.  This  exact  co-ordination  of  inhibition 
and  contraction  is  the  essential  thing  in  peristalsis.  When  the  food 
reaches  the  lower  end  of  the  gullet  the  tonic  contraction  of  that  part 
of  the  tube  is  for  a  moment  relaxed  by  reflex  inhibition,  and  the 
morsel  passes  into  the  stomach.  Beaumont  saw,  in  the  case  of 
St.  Martin,  that  the  oesophageal  orifice  of  the  stomach  contracted 
firmly  after  each  morsel  was  swallowed,  and  so  did  the  gastric  walls 
in  the  neighbourhood  of  the  fistula  when  food  was  introduced  by 
this  opening.  In  the  dog  the  whole  process  of  swallowing  from 
mouth  to  stomach  has  been  shown  to  occupy  four  to  five  seconds, 
but  the  time  is  by  no  means  constant.  In  man  the  peristaltic  wave 
requires  about  five  to  six  seconds  to  travel  from  the  level  of  the 
glottis  to  the  cardiac  orifice.  The  rate  of  movement  is  greater  in  the 
upper  than  in  the  lower  portion  of  the  oesophagus. 

Such  is  the  mechanism  of  deglutition  when  the  bolus  is  of  such 
consistence  and  size  that  it  actually  distends  the  oesophagus.  But 
it  has  been  shown  that  liquid  food  is  swallowed  in  a  different  way. 
The  food  lying  on  the  dorsum  of  the  tongue,  suddenly  put  under 
pressure  by  the  sharp  contraction  of  the  mylo-hyoid  muscles,  is 
shot  rapidly  down  to  the  lower  part  of  the  lax  oesophagus,  or,  occa- 
sionall3^  some  of  it  even  into  the  stomach.  So  far  the  process  has 
only  occupied  one-tenth  of  a  second.  After  several  seconds,  the 
food,  or  the  portion  which  still  remains  in  the  oesophagus,  is  forced 
through  the  cardiac  sphincter  into  the  stomach  by  the  arrival  of 
the  tardy  peristaltic  contraction  of  the  oesophageal  wall  (Ivronecker 
and  Meltzer).  Two  sounds  may  be  heard  in  man  on  listening  in 
the  region  of  the  stomach  or  oesophagus  during  deglutition  of  liquids, 
especially  when,  as  generally  happens,  they  are  mixed  with  air. 
The  first  sound  occurs  at  once,  and  is  due  to  the  sudden  squirt  of 
the  liquid  along  the  gullet ;  the  second,  which  is  heard  after  a  distinct 
interval  (about  six  seconds),  is  caused  by  the  forcing  of  the  fluid 
through  the  cardiac  orifice  of  the  stomach  by  the  contraction  of  the 
oesophagus. 

There  are  certain  peculiarities  which  distinguish  this  peristaltic 
movement  of  the  oesophagus  from  that  of  other  parts  of  the  aUmen- 
tary  canal.  It  is  far  more  closely  related  to  the  central  nervous 
system,  and,  unlike  the  peristaltic  contraction  of  the  intestine,  can 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION  319 

pass  over  any  muscular  block  caused  by  ligature,  section,  or  crush- 
ing, so  long  as  the  nervous  connections  are  intact.  But  division 
of  the  oesophageal  nerves  causes,  as  a  rule,  stoppage  of  oesophageal 
movements;  although  an  excised  portion  of  the  tube  retains  its 
vitality  for  a  long  time,  and  may,  under  certain  circumstances,  go 
on  contracting  in  the  characteristic  way  after  removal  from  the  body 
(p.  790).  Stimulation  of  the  mucous  membrane  of  the  pharynx  will 
cause  reflex  movements  of  the  oesophagus,  while  stimulation  of  its 
own  mucous  membrane  is  ineffective.  From  these  facts  we  learn 
that  although  the  oesophageal  wall  may  possess  a  feeble  power  of 
spontaneous  peristaltic  contraction,  yet  this  is  usually  in  abeyance, 
or  at  least  overmastered  by  central  nervous  control;  so  that  impulses 
discharged  as  a  '  fusillade  '  from  successive  portions  of  the  vagus 
centre,  and  travelling  down  the  oesophageal  nerves,  excite  the 
muscular  fibres  in  regular  order  from  the  upper  to  the  lower  end 
of  the  tube. 

Nervous  Mechanism  of  Deglutition. — The  centre  for  the  whole 
involuntary  stage  (both  phar^iigeal  and  oesophageal)  hes  in  the 
upper  part  of  the  medulla  oblongata.  When  the  brain  is  sliced 
away  above  the  medulla,  deglutition  is  not  affected;  but  if  the  upper 
part  of  the  medulla  is  removed,  the  power  of  swallowing  is  abolished. 
In  man,  disease  of  the  spinal  bulb  interferes  far  more  with  deglutition 
than  disease  of  the  brain  proper. 

Normally,  the  afferent  impulses  to  the  centre  are  set  up  by  the 
contact  of  food  or  sahva  with  the  mucous  membrane  of  the  posterior 
part  of  the  tongue,  the  soft  palate  and  the  fauces,  the  nerve- 
channels  being  the  superior  laryngeal,  the  phar\Tigeal  branches  of 
the  vagus,  and  the  palatal  branches  of  the  fifth  nerve.*  A  feather 
has  sometimes  been  swallowed  involuntarily  by  a  reflex  movement 
of  deglutition  set  up  while  the  soft  palate  or  pharjTix  was  being 
tickled  to  produce  vomiting.  Artificial  stimulation  of  the  central 
end  of  the  superior  laryngeal  will  cause  the  movements  of  deglutition 
independently  of  the  presence  of  food  or  liquid;  but  if  the  central 
end  of  the  glosso- pharyngeal  nerve  be  stimulated  at  the  same  time, 
the  movements  do  not  occur.  The  glosso-pharyngeal  is  therefore 
able  to  inhibit  the  deglutition  centre,  and  it  is  owng  to  the  action 
of  this  nerve  that  in  a  series  of  efforts  at  swallowing,  repeated  within 
less  than  a  certain  short  interval  (about  a  second),  onlv  the  last  is 
successful.  It  is  also  through  the  glosso-pharyngeal  nerve  that 
the  respiratory  movements  are  inhibited  during  deglutition.  When 
the  central  end  of  this  nerve  is  stimulated,  respiration  is  stopped 

*  It  appears  that  the  most  influential  reflex  paths  may  differ  in  ditferent 
animals.  In  the  rabbit,  e.g.,  the  reflex  is  set  up  by  excitation  of  the  trigeminal 
fibres  which  supply  the  mucous  membrane  anterior  to  the  tonsils,  in  the  dog 
and  cat  by  excitation  of  the  glosso-pharyngeal  fibres  in  the  posterior  wall  of 
the  phar\Tix,  and  in  monkeys  by  excitation  of  the  trigeminal  branches  dis- 
tributed to  the  mucous  membrane  over  the  tonsils  (Kahn). 


620  DIGESTION 

for  four  or  five  seconds,  and  this  cessation  is  distinguished  from 
that  produced  by  any  other  afferent  nerve  by  the  circumstance 
that  it  occurs  not  in  expiration  exclusively  or  in  inspiration  ex- 
clusively, but  with  the  respiratory  muscles  in  the  precise  degree  of 
contraction  in  which  they  happened  to  be  at  the  moment  of  stimu- 
lation. The  efferent  nerves  of  the  reflex  act  of  deglutition  are  the 
hypoglossal  to  the  tongue  and  the  thjnro-hyoid  and  other  muscles 
concerned  in  raising  the  larynx;  the  glosso-pharyngeal,  va.jus, 
facial  and  fifth  to  the  muscles  of  the  palate,  fauces,  and  pharynx; 
the  fifth  to  the  mylo-hyoid;  and  the  vagus  to  the  larynx  and 
oesophagus.  Section  of  the  vagus  interferes  with  the  passage  of 
food  along  the  oesophagus;  stimulation  of  its  peripheral  end  causes 
oesophageal  movements. 

Movements  of  the  Stomach. — The  whole  of  the  stomach  does 
not  take  part  equally  in  the  movements  associated  with  digestion. 
We  may  divide  the  organ,  both  anatomically  and  functionally,  into 
two  portions — a  pyloric  portion,  or  antrum  pylori,  comprising  about 
a  fifth  of  the  stomach,  and  a  larger  cardiac  portion,  or  fundus.* 
At  the  junction  of  the  antrum  and  the  fundus  the  circular  muscular 
coat  is  slightly  thickened  into  a  ring  called  the  '  transverse  band,' 
or  '  sphincter  of  the  antrum.'  In  the  living  stomach  the  region 
of  the  transverse  band  is  usually  contracted  so  strongly  and  con- 
tinuously that  a  distinct  groove  is  seen  to  separate  the  tubular 
antrum  from  the  bag-like  cardiac  end.  The  suggestion  of  a  massive 
constricting  ring  of  muscle  is  belied  by  an  examination  of  the  dead 
viscus.  The  transverse  band  is  really  little  more  than  a  physio- 
logical sphincter.  The  empty  stomach  is  contracted  and  at  rest. 
A  few  minutes  after  food  is  taken  contractions  begin  in  the  antrum, 
and  run  on  in  constricting  undulations  (in  the  cat  at  the  rate  of 
six  in  the  minute)  towards  the  pyloric  sphincter.  Each  wave  takes 
about  twenty  seconds  (in  the  cat)  to  pass  from  the  middle  of  the 
stomach  to  the  pylorus.  Feeble  at  first,  they  become  stronger  and 
stronger  as  digestion  proceeds,  and  gradually  come  to  involve  the 
portion  of  the  fundus  next  the  sphincter  of  the  antrum,  but  their 
direction  is  always  towards  the  pylorus,  never,  in  normal  diges- 
tion, away  from  it.  The  food  is  thus  subjected  to  energetic  churn- 
ing movements  in  the  pyloric  end  of  the  stomach,  and  worked  up 
thoroughly  with  the  gastric  juice.  Kept  in  constant  circulation, 
it  gradually  becomes  reduced  to  a  semi-liquid  mass,  the  chyme, 
which  is  at  intervals  driven  against  the  pylorus  by  strong  and 
regular  peristaltic  contractions  of  the  lower  end  of  the  stomach, 

*  Here  '  fundus  '  is  used  in  the  sense  in  which  it  is  generally  employed  in 
speaking  of  the  stomach  of  the  dog  oi  cat  as  signifying  the  wnole  of  the  o.gan 
with  the  exception  of  the  antrum  pyiori.  By  the  fundus  of  the  human  stomach 
most  writers  mean  only  the  cul-de-sac  at  the  cardiac  end;  the  portion  inter- 
vening between  it  and  the  aiicrum  pylori  is  often  termei  the  body  of  the 
stomach. 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION 


321 


II  AM 


the  sphincter  relaxing  from  time  to  time  by  a  reflex  inhibition  to 
admit  the  better-digested  portions  into  the  duodenum,  but  tighten- 
ing more  stubbornly  at  the  impact  of  a  hard  and  undigested  morsel. 
The  nature,  as  well  as  the  consistence  of  the  food,  influences  the 
length  of  its  sojourn  in  the  stomach.  Carbo-hydrate  food  passes 
more  rapidly  through  the  pylorus  than  fatty  food,  and  fat  more 
rapidly  than  protein.  The  reason  is  that 
the  acidity  of  the  gastric  juice  varies 
with  the  different  kinds  of  food,  hydro- 
chloric acid  being  secreted  in  abundance 
in  the  presence  of  proteins,  and  to  a 
much  smaller  extent  in  the  presence  of 
fats  and  carbo-hydrates.  Now,  dilute 
hydrochloric  acid  when  introduced  into 
the  stomach  remains  there  for  a  much 
longer  time  than  water.  This  depends 
upon  the  fact  that  such  portions  of  the 
acid  as  get  into  the  duodenum  stimulate 
afferent  fibres  in  its  mucous  membrane, 
and  so  cause  reflex  spasm  of  the  pyloric 
sphincter.  When  the  acid  chyme  be- 
comes neutralized  to  a  certain  point  by 
the  bile  and  pancreatic  juice,  inhibitory 
impulses  pass  up  from  the  duodenum 
and  cause  the  sphincter  to  relax.  The 
cardiac  division  of  the  stomach,  with 
the  exception  of  the  portion  that  borders 
the  transverse  band,  takes  no  share  in 
the  peristaltic  movements.  And,  indeed, 
it  is  far  more  difficult  to  cause  such  con- 
tractions by  artificial  stimulation  in  the 
fundus  than  in  the  pylorus.  The  two 
portions  of  the  stomach  are  partially,  or 
in  certain  animals  from  time  to  time 
completely,  cut  off  from  each  other  by 
the  contraction  of  the  sphincter  of  the 
antrum.  The  fundus,  so  far  as  its 
mechanical  functions  are  concerned,  acts 
chiefly  as  a  reservoir  for  the  food,  which, 
like  a  hopper,  it  gradually  passes  into 
the  pyloric  mill  as  digestion  goes  on  by  a  tonic  contraction  of  its 
walls.  The  existence  of  this  reservoir  enables  larger  quantities  of 
food  to  be  taken  at  one  meal,  which  can  then  be  digested  gradually. 
These  facts  have  been  mainly  ascertained  by  observations  on 
animals,  such  as  the  dog  and  the  cat,  either  by  direct  inspection 
after  opening  the  abdomen  (Rossbach),  or  in  the  intact  body,  under 


Fig.  150. — Cat's  Stomach  seen 
by  Kontgen  Rays  (Cannon). 
The  outlines  of  the  stomach 
containing  food  mi.xed  with 
bismuth  subnitrate  were 
drawn  at  intervals  from 
II  a.m.  to  4.30  p.m. 


322 


DIGESTION 


absolutely  physiological  conditions,  by  means  of  the  Rontgen  rays 
(Cannon).  In  the  latter  method  the  food  is  mixed  with  subnitrate 
of  bismuth,  which  is  opaque  to  these  rays,  so  that  when  the  animal 
is  looked  at  through  a  fluorescent  screen  the  stomach  appears  as  a 
dark  shadow  in  the  field  (Fig.  150).  This  method  has  even  been 
applied  with  success  to  the  study  of  the  passage  of  the  food  along 
the  human  alimentary  canal  from  deglutition  to  defgecation  (Hertz). 
It  has  been  shown  in  this  way  that  in  the  living  body  in  the  erect 
position  the  long  axis  of  the  stomach  is  much  more  nearly  v;^rtical 
than  had  been  supposed.  When  food  is  taken  it  sinks  into  the 
lower  (pyloric)  end,  and  at  the  upper  end  gas  collects. 

When  the  person  lies  down  the  lower  end  of  the  stomach  passes 
more  towards  the  left,  so  that  the  long  axis  lies  more  transversely. 
Other  methods  have  thrown  Hght  on  the  gastric  movements — e.g., 
direct  inspection  through  a  fistula  of  the  stomach,  and  the  study 


Fig.  151. — Human  Stomach  studied  by  Rontgen  Rays,  a.  Empty  stomach  in  ver- 
tical position  ;  6,  shortly  after  a  meal  (peristaltic  contractions  are  occurring  at 
the  pyloric  end) ;  c,  full  stumac'i  in  vertical  position.     (Halliburton  after  Hertz.) 

of  records  showing  the  changes  of  pressure  in  the  viscus  obtained 
by  means  of  small  balloons  introduced  into  it.  Such  balloons 
attached  to  a  rubber  tube  have  been  swallowed  by  normal  men 
and  kept  for  long  periods  in  the  stomach  (Carlson).  Even  in  the 
excised  stomach,  kept  in  salt  solution  at  the  body-temperature, 
the  typical  movements  can  be  observed  proceeding  for  some  time. 
Movements  of  the  Small  Intestine. — In  the  small  intestine  two 
kinds  of  movements  are  to  be  seen:  (i)  Gentle,  swaying, '  pendulum  ' 
movements,  sometimes  irregular,  but  often  recurring  rhythmically 
at  the  rate  (in  the  dog)  of  10  or  12  in  the  minute.  Both  the  longi- 
tudinal and  the  circular  muscular  coats  contract,  causing  slight 
waves  of  constriction,  which  may  originate  at  any  part  of  the  gut, 
but,  under  normal  circumstances,  nearly  always  travel  from  above 
downwards,  with  a  velocity  of  2  to  5  centimetres  per  second.  These 
movements  cause  the  coils  of  the  intestine  to  sway  gently  from  side 
to  side.  Under  abnormal  conditions,  as  in  the  exposed  '  surviving  ' 
intestines   of  the   rabbit,    contractions,    probably   similar  to   the 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION  3'^3 

pendulum  movements,  but  running  indifferently  in  both  direc- 
tions, can  be  set  up  by  local  stimulation.  The  function  of  these 
pendulum  movements  seems  to  be  the  thorough  mixing  of  the  food 
with  the  digestive  juices  in  the  intestine.  When  an  animal  is  fed 
with  food  containing  bismuth  subnitrate  and  observed  with  the 
Rontjjen  rays,  it  is  seen  that  the  food  in  a  coil  is  often  divided  into 
small  segments,  which  then  join  together  to  form  longer  masses, 
these  being  in  turn  again  divided.  This  segmentation  is  rhyth- 
mically repeated  (in  the  cat  at  the  rate  of  thirty  times  a  minute). 
Although  of  itself  it  insures  only  the  mixing  of  the  contents  of  the 
gut,  and  not  their  onward  progress,  it  is  usually  accompanied  by 
peristalsis,  so  that  while  the  food  is  undergoing  segmentation  it  is 
also  slowly  passing  down  the  intestine.  Often,  however,  a  column 
of  food  remains  for  a  considerable  time,  dividing,  uniting,  and  divid- 
ing again,  without  sensibly  shifting  its  position.  In  addition  to  the 
relatively  rapid  pendulum  movements,  much  slower  periodic  varia- 
tions of  tone  of  the  whole  musculature  may  be  normally  observed. 

(2)  True  peristaltic  movements,  in  which  a  ring  of  constriction, 
obliterating  the  lumen,  moves  slowly  down  the  tube,  with  a  speed, 
it  may  be,  no  greater  than  i  mm.  per  second.  The  portion  of  the 
intestine  immediately  below  the  advancing  constriction  is  relaxed 
and  motionless,  so  that  we  may  say  that  a  wave  of  inhibition  pre- 
cedes the  wave  of  contraction.  Th6  peristaltic  movements  of  the 
small  intestine,  the  most  typical  of  their  kind,  are  most  easily 
excited  by  mechanical  stimulation  of  the  mucous  membrane,  as 
by  the  contact  of  a  morsel  of  food  or  an  artificial  bolus  of  cotton- 
wool. Travelling,  under  normal  conditions,  always  downwards, 
the  constriction  squeezes  the  contents  of  the  tube  before  it,  and  the 
wave  usually  ends  at  the  ileo-cascal  valve,  which  separates  the  small 
intestine  from  the  large.  The  cause  of  the  definite  direction  of  the 
peristaltic  wave  is  grounded  in  the  anatomical  relations  of  the 
intestinal  wall.  For  when  a  portion  of  the  intestine  is  resected, 
turned  round  in  its  place  and  sutured,  so  that  what  was  before  its 
upper  is  now  its  lower  end,  the  contraction  wave  is  unable  to  pass, 
and  the  obstruction  to  the  onward  flow  of  the  intestinal  contents 
causes  marked  dilatation  of  the  gut,  and  sometimes  serious  disturb- 
ance of  nutrition.  The  most  probable  explanation  is  that  the  peri- 
stalsis is  governed  by  a  local  reflex  nervous  mechanism  (Auerbach's 
plexus),  the  stimulation  of  which  by  the  contact  of  the  food  with 
the  mucous  membrane  or  by  the  distension  of  the  gut  causes 
excitation  of  the  circular  muscular  fibres  above  the  point  of  stimula- 
tion, and  inhibition  of  them  below  it.  The  automatic  pendulum 
movements,  and  also  the  slow,  rhythmical  variations  of  tone,  have 
a  different  relation  to  the  local  nervous  mechanism,  for  they  behave 
differently  to  poisons  like  cocaine  and  nicotine,  which  act  on  that 
mechanism.     The  pendulum  movements  are,  if  anything,  increased 


324 


DIGESTION 


in  intensity  and  made  more  regular.  But  the  peristaltic  waves, 
although  they  can  be  locally  excited  by  direct  stimulation  of  the 
muscular  fibres,  are  no  longer  propagated,  and  a  bolus  introduced 
into  the  intestine  remains  at  rest  where  it  is  placed.  Some  have 
interpreted  these  facts  as  indicating  that  the  pendulum  movements 
are  myogenic  in  origin.  But  evidence  has  lately  been  obtained  that, 
although  they  are  not  reflex  movements  elicited  by  afferent  impulses 
from  the  mucous  membrane,  since  they  continue  in  unaltered  in- 
tensity, in  isolated  loops  of  intestine  immersed  in  Ringer's  (or 
Locke's)  solution  (p.  66)  after  removal  of  both  mucosa  and  sub- 
mucosa,  they  are  nevertheless  dependent  upon  Auerbach's  plexus. 
For  when  the  circular  muscular  coat  is  separated  from  this  plexus, 
the  automatic  movements  of  this  coat  are  abolished,  although  the 

excitability  of  the  musculature  to 
direct  stimulation  is  not  affected. 
The  longitudinal  coat,  which  is 
still  in  connection  with  Auerbach's 
plexus,  goes  on  contracting  spon- 
taneously (Magnus).  Under  certain 
conditions  a  movement  of  food  or 
secretions  in  the  reverse  of  the 
normal  direction  can  be  set  up  in 
the  small  intestine  in  the  intact 
body — -e.g.,  in  the  case  of  obstruc- 
tion of  the  intestine  leading  to 
vomiting  of  its  contents.  But  this 
does  not  necessarily  indicate  a  re- 
versal of  the  normal  direction  of 
the  peristalsis.  Such  a  reversal, 
if  it  occurs  at  all,  is  not  easy  to  realize  by  artificial  stimulation,  and 
even  when  an  antiperistaltic  wave  is  apparently  started,  it  travels 
up  the  intestine  only  for  a  short  distance  and  then  dies  out.  A 
third  variety  of  intestinal  movement  has  sometimes  been  described, 
the  so-called  '  peristaltic  rush  '  (Meltzer,  etc.).  It  consists  of  a 
rapidly  moving  peristaltic  contraction,  preceded  by  relaxation  of 
a  long  portion  of  the  tube.  Such  a  contraction  may  even  sweep 
down  without  pause  from  the  duodenum  to  the  end  of  the  ileum. 

The  Movements  of  the  Large  Intestine  differ  from  those  of  the 
small  mainly  in  the  great  frequency  of  antiperistalsis.  This,  indeed, 
seems  to  be  the  usual  movement  of  the  transverse  and  ascending 
colon.  The  antiperistalsis  recurs  in  periods  about  every  fifteen 
minutes,  and  each  period  generally  lasts  about  five  minutes.  The 
constrictions,  running  towards  the  caecum,  thoroughly  churn  and 
mix  the  remnants  of  the  food,  a  considerable  absorption  of  which 
may  take  place  in  the  upper  part  of  the  large  intestine.  Regurgita- 
tion into  the  ileum  in  man  is  prevented  partly  by  the  obhque  entry 


Fig.  152. — Intestine  Segment  beating 
in  Ringer's  Solution.  At  6  the  oxy- 
gen stream  was  increased.  To  be 
read  from  left  to  right.  Time  trace, 
half -minutes.    ( Reduced  to  one  -half . ) 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION  325 

of  the  ileum  through  the  wall  of  the  colon  (so-called  ileo-caecal 
valve),  but  essentially  by  the  tonic  contraction  of  the  ileo-colic 
sphincter.  The  sphincter  usually  permits  the  passage  of  material 
only  in  the  direction  from  small  to  large  intestine.  But  as  an 
occasional  phenomenon,  a  reverse  movement  may  occur.  Thus 
food  may  actually  pass  back  through  the  ileo-colic  sphincter  into 
the  small  intestine  under  the  action  of  a  long-continued  and  vigorous 
antiperistalsis,  and  in  this  way  a  considerable  portion  of  a  bulky 
enema  may  be  eventually  disposed  of  (Cannon).  This  so-called 
antiperistalsis  is  not  precisely  the  same  kind  of  movement,  leaving 
out  of  account  its  direction,  as  the  peristalsis  already  described  in  the 
small  intestine,  since  it  is  not  preceded  by  a  wave  of  inhibition. 
True  peristaltic  contractions  preceded  by  relaxation  of  the  gut  may 
also  be  observed  to  start  in  the  caecum,  and  to  travel  down  the  large 
intestine.  They  are  not  very  frequent  in  comparison  with  those 
of  the  small  intestine,  and  they  die  away  before  reaching  the  end 
of  the  colon,  allowing  the  food  to  be  driven  back  again  towards 
the  caecum  by  the  antiperistalsis.  A  true  downward  peristalsis 
is  more  commonly  seen  in  the  descending  colon,  and  is  here  asso- 
ciated with  the  propulsion  and  collection  of  the  faeces,  which  are 
mainly  stored  in  the  sigmoid  flexure.  These  peristaltic  contractions 
do  not  normally  reach  the  rectum,  which,  except  during  defaecation, 
remains  at  rest. 

Influence  of  the  Central  Nervous  System  on  the  Gastro- Intestinal 
Movements. — As  we  have  already  said,  these  movements  are  much 
less  closely  dependent  on  the  central  nervous  system  than  are  those 
of  the  oesophagus.  They  can  not  only  go  on,  but  are  in  general 
better  marked  when  the  extrinsic  nervous  connections  are  cut ;  they 
cannot  spread  when  the  continuity  of  the  tube  is  destroyed,  and 
the  mere  presence  of  food  will  excite  them  when  other  than  local 
reflex  action  has  been  excluded  by  section  of  the  nerves.  Never- 
theless, the  central  nervous  system  does  exercise  some  influence 
in  the  way  of  regulation  and  control,  if  not  in  the  way  of  direct 
initiation  of  the  movements,  and  the  swallowing  or  even  the  smell 
of  food  has  been  observed  to  strengthen  the  contractions  of  a  loop 
of  intestine  severed  from  the  rest,  but  with  its  nerves  still  intact. 
The  vagus  is  the  efferent  channel  of  this  reflex  action:  stimulation 
of  its  peripheral  end  may  cause  movements  of  all  parts  of  the 
alimentary  canal  from  oesophagus  to  large  intestine,  and  may 
strengthen  movements  already  going  on;  but  section  of  it  does  not 
stop  them,  nor  hinder  the  food  from  causing  peristalsis  wherever 
it  comes.  The  vagus  also  contains  inhibitory  fibres  for  the  lower 
end  of  the  oesophagus  and  the  whole  of  the  stomach.  Stimulation 
of  it  is  followed  first  by  inhibition,  and  then,  after  an  interval,  by 
an  increase  of  tone  and  augmentation  of  the  contraction  of  the 
whole  stomach,  including  the  cardiac  and  pyloric  sphincters.     The 


336  DIGESTION 

splanchnic  nerves  contain  fibres  by  which  the  intestinal  movements 
can  be  inhibited,  and  they  appear  to  be  always  in  action,  for  after 
section  of  these  nerves  the  movements  are  strengthened.  On  the 
other  hand,  stimulation  of  the  peripheral  end  of  the  cut  splanchnic 
causes  arrest  of  the  movements.  Occasionally,  however,  it  has 
the  opposite  effect.  Contractions  of  the  small  intestine  are  more 
easily  caused  by  excitation  of  the  vagus  after  the  inhibitory  splanch- 
nic nerves  have  been  cut.  The  splanchnics  also  contain  inhibitory 
fibres  for  the  stomach,  and  it  is  only  when  these  are  intact  that 
complete  reflex  inhibition  of  the  organ  can  be  obtained  in  the  rabbit 
(Auer).  The  gastric  movements  are  not  permanently  affected  by 
section  of  these  nerves  alone,  or  even  by  simultaneous  section  of 
the  splanchnics  and  the  gastric  branches  of  the  vagi.  But  if  the 
vagi  are  cut  while  the  splanchnics  remain  intact,  the  peristalsis  of 
the  stomach  is  weakened,  its  onset  delayed,  and  the  proper  emptying 
of  the  viscus  through  the  pylorus  interfered  with.  In  all  probability 
these  results  are  due  to  the  uncontrolled  action  of  the  inhibitory 
fibres.  The  splanchnics  have  a  special  relation  to  the  ileo-colic 
sphincter,  which  closes  when  they  are  stimulated,  and  becomes  in- 
sufficient when  they  are  cut.     The  vagus  does  not  affect  it. 

The  lower  part  of  the  large  intestine  is  influenced  by  the  sacral  nerves 
(second,  third,  and  fourth  sacral  in  tlie  rabbit),  and  by  certain  lumbar 
nerves,  in  the  same  way  as  the  higher  parts  of  the  alimentary  canal,  and 
particularly  the  small  intestine,  arc  influenced  by  the  vagus  and  the 
splanchnics.  Stimulation  of  these  sacral  nerves  within  the  spinal 
canal,  or  of  the  pelvic  nerves  (nervi  erigentes)  into  which  they  pass, 
causes  contraction  of  the  parts  of  the  large  intestine  concerned  in 
defaBcation — ^that  is,  in  the  dog,  of  the  whole  colon,  with  the  exception 
of  the  caecum;  in  the  cat,  of  the  distal  two-thirds  of  the  colon.  The 
colon  first  undergoes  rapid  shortening  due  to  the  contraction  of  the 
longitudinal  fibres  and  the  recto-coccygeus  muscle.  After  a  few 
seconds  this  is  followed  by  contraction  of  the  circular  fibres,  beginning 
at  the  lower  limit  of  the  region  in  which  antiperistalsis  can  occur,  and 
spreading  downwards,  so  as  to  empty  the  portion  of  the  bowel  involved 
in  the  contraction.  This  is  a  very  close  imitation  of  what  occurs  in 
natural  defaecation.  In  man  the  parts  involved  in  these  movements 
are  probably  the  sigmoid  flexure  and  rectum.  In  addition  to  these 
characteristic  motor  effects  on  the  lower  part  of  the  large  intestine, 
stimulation  of  the  pelvic  nerves  causes  an  increase  in  the  antiperistalsis 
of  its  upper  portions.  Stimulation  of  the  lumbar  nerves  or  of  the  por- 
tions of  the  sympathetic  into  which  their  visceral  fibres  pass  (lumbar 
sympathetic  chain  from  second  to  sixth  ganglia,  or  the  rami  from  it  to 
the  inferior  mesenteric  ganglia)  causes  inhibition  of  the  movements  of 
the  caecum  and  the  whole  colon,  including  the  antiperistaltic  move- 
ments. Excitation  of  the  sacral  nerves  initiates  or  increases  the  con- 
traction of  both  coats  of  the  portions  of  the  large  intestine  on  which 
they  act,  excitation  of  the  lumbar  nerves  inhibits  both.  And  in  the  small 
intestine  the  same  law  holds  good ;  the  two  coats  are  contracted  together 
by  the  action  of  the  vagus  or  inhibited  together  by  that  of  the  splanchnics. 

Defaecation  is  partly  a  voluntary  and  partly  a  reflex  act.     But 
in  the  infant  the  voluntary  control  has  not  yet  been  developed; 


THE  MECHANICAL  PHENOMENA  OF  DIGESTION  327 

in  the  adult  it  may  be  lost  by  disease;  in  an  animal  it  may  be 
abolished  by  operation,  and  in  each  case  the  action  becomes  wholly 
reflex.  Owing  to  the  tonic  contraction  of  the  rectum  and  the  acute 
angle  formed  at  the  pelvi-rectal  flexure,  the  faeces  are  arrested  at 
this  point.  In  consequence  the  pelvic  colon  becomes  filled  with 
faeces  from  below  upwards,  and  the  rectum  remains  empty  till 
immediately  before  defaecation.  This  has  been  verified  in  man  by 
observations  with  the  Rontgen  rays  (Hertz).  In  persons  whose 
bowels  are  opened  regularly  after  breakfast,  the  passage  of  faeces 
into  the  rectum  gives  rise  to  the  characteristic  sensation  which 
may  be  termed  the  '  call  to  defaecation.'  It  is  the  distension  of  the 
rectum,  and  of  the  rectum  alone,  which  is  associated  with  this 
sensation,  for  in  persons  from  whom  the  entire  rectum  has  been 
removed  for  malignant  disease  the  sensation  is  absent,  and  it  may 
be  elicited  by  artificially  distending  the  rectum,  though  not  any 
other  part  of  the  alimentary  canal.  The  minimum  pressure  required 
to  elicit  the  sensation  is  smaller  the  greater  the  length  of  the  gut 
exposed  to  it,  varying  in  one  individual  from  32  to  48  mm.  of 
mercury,  according  to  the  length  of  a  balloon  introduced  into  the 
rectum.  The  passage  of  the  faeces  from  the  pelvic  colon  into  the 
rectum  is  due  to  the  discharge  of  that  reflex  contraction  of  the  lower 
portion  of  the  bowel  already  described  (p.  325),  of  which  the  pelvic 
nerves  constitute  the  efferent  path.  This  reflex  peristalsis  is  elicited 
by  various  causes,  among  which  one  of  the  most  important  is  the 
taking  of  food  at  breakfast  into  the  empty  stomach,  and  another 
the  muscular  activity  associated  with  getting  up  and  dressing. 
The  desire  to  defaecate  may  for  a  time  be  resisted  by  the  will,  or  it 
may  be  yielded  to.  In  the  latter  case  the  abdominal  muscles,  and, 
according  to  Hertz,  the  diaphragm  also,  are  forcibly  contracted; 
and  the  glottis  being  closed,  the  whole  effect  of  their  contraction 
is  expended  in  raising  the  pressure  within  the  abdomen  and  pelvis, 
and  so  aiding  the  muscular  wall  of  the  bowel  itself  in  driving  the 
faeces  from  the  sigmoid  flexure  to  the  rectum.  The  two  sphincters 
which  close  the  anus — the  internal  sphincter  of  smooth  muscle, 
and  the  external  of  striated — are  now  relaxed  by  the  inhibition  of 
a  centre  in  the  lumbar  portion  of  the  spinal  cord,  through  the 
activity  of  which  the  tonic  contraction  of  the  sphincters  is  normally 
maintained.  This  relaxation  is  partly  voluntary,  the  impulses 
that  come  from  the  brain  acting  probably  through  the  medium 
of  the  lumbar  centre.  'But  in  the  dog,  after  section  of  the  cord  in 
the  dorsal  region,  the  whole  act  of  defaecation,  including  contraction 
of  the  abdominal  muscles  and  relaxation  of  the  sphincters,  still 
takes  place,  and  here  the  process  must  be  purely  reflex.  Even  after 
complete  destruction  of  the  lumbar  and  sacral  portions  of  the  spinal 
cord  the  tone  of  the  sphincters  returns  after  a  time,  and  defaecation 
is  carried  on  as  in  a  normal  animal,  the  control  of  the  sphincters 


328  DIGESTION 

being  due  either  to  a  property  of  the  muscular  tissue  itself  or  to 
local  ganglia.  The  contraction  of  the  levatores  ani  helps  to  resist 
overdistension  of  the  pelvic  floor  and  to  pull  the  anus  up  over  the 
faeces  as  they  escape.  The  nervi  erigentes  carry  efferent  constrictor 
fibres,  and  the  hypogastrics,  as  a  rule,  efferent  dilator  fibres,  to  the 
sphincters.  While  the  internal  sphincter  is  by  itself  capable  of 
maintaining  a  tonus  of  considerable  strength,  the  external  sphincter 
contributes  an  important  share  (30  to  60  per  cent.)  to  the  closure 
of  the  rectum.  If  the  call  to  defsecation  is  neglected,  the  desire 
passes  away.  This  is  not  due  to  the  faeces  being  carried  back  into 
the  pelvic  colon  by  antiperistalsis,  as  has  generally  been  stated. 
The  faeces  which  have  passed  into  the  rectum  remain  there,  as  can 
be  shown  by  examination  with  the  finger  after  the  desire  to  empty 
the  bowels  has  disappeared.  The  reason  for  the  disappearance 
of  the  sensation  is  the  relaxation  of  tone  which  occurs  in  the 
muscular  coat  of  the  rectum  after  a  period  of  distension.  It  is  not 
till  it  has  been  again  distended  by  the  entrance  of  a  further  portion 
of  faeces  that  the  call  to  defaecation  is  again  experienced.  When 
the  call  is  repeatedly  neglected,  the  sensibility  of  the  rectum  to  dis- 
tension becomes  blunted,  and  this  is  a  common  cause  of  constipation. 

The  time  of  passage  of  substances  through  the  alimentary  canal 
has  been  studied  by  administering  collodion  capsules  filled  with 
subnitrate  of  bismuth  to  human  beings,  and  observing  their  pro- 
gress by  taking  shadow  pictures  of  them  at  intervals  with  the 
Rontgen  rays.  During  the  first  twenty  minutes  two  such  capsules 
swallowed  at  the  same  time  by  a  healthy  young  man  were  clearly 
seen  in  the  greater  curvature  of  the  stomach,  but  in  the  interval 
between  the  first  half-hour  and  the  seventh  or  eighth  hour  no  further 
trace  of  them  was  detected.  About  the  eighth  hour  they  re- 
appeared in  the  caecum,  where  they  remained  with  little  or  no 
onward  movement  till  the  fourteenth  hour.  From  the  fourteenth 
to  the  sixteenth  hour  they  travelled  along  the  ascending  colon,  and 
tarried  a  long  time  at  the  left  angle  of  the  colon.  From  the  nine- 
teenth to  the  twenty-second  or  twenty-fourth  hour  they  slowly 
passed  downward  in  the  descending  colon,  and  stopped  at  the  sig- 
moid flexure  till  their  expulsion  in  defaecation.  In  some  subjects 
the  entire  passage  of  the  capsules  was  complete  in  sixteen  hours,  in 
others  not  until  after  thirty  hours.  A  one  cent  piece  swallowed  by 
a  healthy  child  four  years  old  was  recovered  in  the  faeces  52  hours 
later,  and  a  button,  shghtly  larger,  swallowed  by  the  same  child, 
appeared  after  almost  exactly  the  same  interval. 

Vomiting. — We  have  seen  that  under  normal  conditions  the 
movements  of  the  alimentary  canal  always  tend  to  carry  the  food 
in  one  definite  direction,  along  the  tube  from  the  mouth  to  the 
rectum.  The  peristaltic  waves  generally  run  only  in  this  direction, 
and,   further,   regurgitation  is  prevented  at  three  points  by  the 


THE  MECHANICAL  PHENOMENA   OF  DIGESTION  329 

cardiac  and  pyloric  sphincters  of  the  stomach  and  the  ileo-colic 
sphincter  and  valve.  But  in  certain  circumstances  the  peristalsis 
may  be  reversed,  one  or  more  of  the  guarded  orifices  forced,  and  the 
onward  stream  of  the  intestinal  contents  turned  back.  In  obstruc- 
tion of  the  bowel,  the  faecal  contents  of  the  large  intestine  may  pass 
up  beyond  the  ileo-caecal  valve,  and,  reaching  the  stomach,  be  driven 
by  an  act  of  vomiting  through  the  cardiac  orifice;  in  what  is  called 
a  '  bilious  attack,'  the  contents  of  the  duodenum  may  pass  back 
through  the  pylorus  and  be  ejected  in  a  similar  way;  or,  what  is 
by  far  the  most  common  case,  the  contents  of  the  stomach  alone 
may  be  expelled. 

Vomiting  is  usually  preceded  by  a  feeling  of  nausea  and  a  rapid 
secretion  of  saliva,  which  perhaps  serves,  by  means  of  the  air 
carried  down  with  it  when  swallowed,  to  dilate  the  cardiac  orifice 
of  the  stomach,  but  may  be  a  mere  by-play  of  the  reflex  stimula- 
tion bringing  about  the  act.  The  diaphragm  is  now  forced  down 
upon  the  abdominal  viscera,  first  with  open  and  then  with  closed 
glottis.  The  thoracic  portion  of  the  oesophagus  is  thus  placed 
under  diminished  pressure,  and  therefore  widened,  while  sahva  and 
air  are  aspirated  into  it  out  of  the  mouth.  The  abdominal  muscles 
strongly  contract.  At  the  same  time  the  stomach  itself,  and  par- 
ticularly the  antrum  pylori,  contracts,  the  cardiac  orifice  relaxes, 
and  the  gastric  contents  are  shot  up  into  the  lax  oesophagus,  and 
through  it  into  the  pharynx,  and  issue  by  the  mouth  or  nose.  The 
movements  of  the  stomach  during  vomiting  induced  by  apomorphine 
have  been  studied  in  the  cat  by  the  Rontgen  ray  method.  There  is 
first  observed  extreme  relaxation  of  the  cardiac  end;  then  a  deep 
constriction  appears  a  little  below  the  cardiac  orifice,  and  runs 
towards  the  pylorus,  increasing  in  depth  as  it  goes.  When  the 
transverse  band  is  reached,  this  contracts  firmly  and  remains  con- 
tracted, and  the  constriction  passes  on  over  the  antrum  pylori. 
Ten  or  twelve  similar  waves  follow,  at  the  end  of  which  time  the 
constriction  in  the  region  of  the  transverse  band  divides  the  stomach 
into  the  firmly-contracted  antrum  and  the  relaxed  fundus.  Now 
follows  a  sudden  contraction  of  the  diaphragm  and  abdominal 
muscles  accompanied  by  the  opening  of  the  cardiac  orifice.  Either 
the  diaphragm  and  abdominal  muscles  alone,  without  the  stomach, 
or  the  diaphragm  and  stomach  together,  without  the  abdominal 
muscles,  can  carry  out  the  act  of  vomiting.  For  an  animal  whose 
stomach  has  been  replaced  by  a  bladder  filled  with  water  can  be 
made  to  vomit  by  the  administration  of  an  emetic  (Magendie) ; 
and  Hilton  saw  that  a  man  who  lived  fourteen  years  after  an  injury 
to  the  spinal  cord  at  the  height  of  the  sixth  cervical  nerve,  which 
caused  complete  paralysis  below  that  level,  could  vomit,  though 
with  great  difficulty.  In  a  young  child  in  which  very  slight  causes 
will  induce  vomiting,  the  stomach  alone  contracts  during  the  act. 


330  DIGESTION 

But  in  the  adult  such  a  contraction  is  ineffectual,  and  the  same  is 
the  case  in  animals,  for  a  dog  under  the  influence  of  a  moderate 
dose  of  curara,  which  paralyzes  the  voluntary  muscles  but  not  the 
stomach,  cannot  vomit. 

The  nerve-centre  is  in  the  medulla  oblongata.  It  may  be 
excited  by  many  afferent  channels:  the  sensory  nerves  of  the  fauces 
or  pharynx,  of  the  stomach  or  intestines  (as  in  strangulated  hernia), 
of  the  liver  or  kidney  (as  in  cases  of  gall-stone  or  renal  calculi),  of 
the  uterus  or  ovary,  and  of  the  brain  (as  in  cerebral  tumour),  are 
all  capable,  when  irritated,  of  causing  vomiting  by  impulses  passing 
along  them  to  the  vomiting  centre. 

The  vagus  nerve  in  man  certainly  contains  afferent  fibres  by  the 
stimulation  of  which  this  centre  can  be  excited,  for  it  has  been 
noticed  that  when  the  vagus  was  exposed  in  the  neck  in  the  course 
of  an  operation,  the  patient  vomited  whenever  the  nerve  was 
touched  (Boinet,  quoted  by  Gowers).  In  meningitis,  vomiting  is 
often  a  prominent  symptom,  and  is  sometimes  due  to  irritation  of 
the  vagus  nerve  by  the  inflammatory  process. 

Some  drugs  act  as  emetics  by  irritating  surfaces  in  which  efficient 
afferent  impulses  may  be  set  up,  the  gastric  mucous  membrane, 
for  example;  sulphate  of  zinc  and  sulphate  of  copper  act  mainly 
in  this  way.  Apomorphine,  on  the  other  hand,  stimulates  the 
centre  directly,  and  this  is  also  the  mode  in  which  vomiting  is  pro- 
duced in  certain  diseases  of  the  medulla  oblongata.  The  efferent 
nerves  for  the  diaphragm  are  the  phrenics,  for  the  abdominal 
muscles  the  intercostals.  The  impulses  which  cause  contraction 
of  the  stomach  pass  along  the  vagi.  Dilatation  of  the  cardiac 
orifice  is  brought  about  by  the  inhibitory  fibres  in  the  vagus  already 
mentioned. 


Section  III. — ^The  Chemistry  of  the     igestive  Juices. 

Ferments. — The  chemical  changes  wrought  in  the  food  as  it 
passes  along  the  alimentary  canal  are  due  to  the  secretions  of 
various  glands  which  line  its  cavities  or  pour  their  juices  into  it 
through  special  ducts.  These  secretions  owe  their  power  for  the 
most  part  to  substances  present  in  them  in  very  small  amount, 
but  which,  nevertheless,  act  with  extraordinary  energy  upon  the 
various  constituents  of  the  food,  causing  profound  changes  with- 
out, upon  the  whole,  being  themselves  used  up,  or  their  digestive 
power  affected.  The  active  agents  are  the  enzymes,  sometimes 
spoken  of  as  unformed  or  unorganized  ferments — unorganized 
because  their  action  does  not  depend  upon  the  growth  of  living 
cells,  which  was  long  supposed  to  be  the  case  for  some  other  fer- 
ments, such  as  yeast.  Since  it  has  been  shown  that  specific  enzymes 
can  be  separated  from  cells  which  were  formerly  believed  to  act 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  331 

by  their  mere  growth,  the  distinction  between  formed  and  unformed 
ferments  has  lost  its  significance,  and  has  to  a  great  extent  been 
superseded  by  the  distinction  between  intra-  and  extra-cellular 
enzymes  (also  called  endo-  and  exo-enzymes)  —  i.e.,  between 
ferments  which  normally  act  in  the  interior  of  the  cells  where  they 
are  produced  and  ferments  which  act  outside  of  the  cells  that  secrete 
them.  From  yeast  cultures,  for  instance,  by  crushing  the  cells, 
a  ferment  (zymase*)  can  be  obtained  which  in  the  complete  absence 
of  living  yeast-cells,  and,  indeed,  of  any  living  micro-organism,  forms 
alcohol  and  carbon  dioxide  from  sugar,  just  as  living  yeast  does. 
There  is  every  reason  to  believe  that  it  is  by  the  intracellular  action 
of  this  endoenzyme  that  the  yeast-cell  normally  causes  alcoholic 
fermentation.  The  digestive  ferments  are  typical  extracellular 
enzymes.  Their  chemical  nature  has  not  been  exactly  made  out; 
some  of  them  at  least  do  not  appear  to  be  proteins,  or  to  contain 
a  protein  group.  Many  of  them  apparently  exist  in  th£  colloidal 
condition,  although  this  has  not  been  shown  for  all.  In  certain 
cases  the  more  or  less  stable  union  of  a  definite  inorganic  substance 
with  the  ferment,  or  its  actual  inclusion  in  the  ferment  molecule, 
seems  to  be  a  condition  of  its  action.  Thus  there  is  reason  to  believe 
that  in  gastric  digestion  hydrochloric  acid  is  loosely  combined  with 
the  pepsin.  In  the  plant  oxydase,  laccase  (p.  268),  manganese  is 
present.  And  the  fact  that  manganese  salts  oxidize  certain  substances 
as  laccase  does  suggests  that  it  is  the  manganese  in  combination 
with  some  protein  or  other  organic  compound  in  the  ferment 
molecule  which  confers  upon  laccase  its  oxidizing  power.  A  similar 
relation  between  iron  and  some  animal  oxydases  is  possible,  though 
not  definitely  proved.  But  none  of  the  ferments  of  the  digestive 
juices  has  as  yet  been  satisfactorily  isolated,  and  at  present  it  is 
only  by  their  effects  that  we  recognize  them.  The  difficulty  of 
isolating  them  is  increased  by  the  fact  that,  like  other  colloids, 
they  readily  adhere  to  surfaces,  and  are  carried  down  by  the  most 
diverse  precipitates  of  substances  to  which  they  are  chemically 
indifferent.  On  the  other  hand,  this  very  property  is  taken  advan- 
tage of  to  procure  more  concentrated,  although  still  impure,  solutions 
of  them  than  e.xist  in  the  natural  secretions.  Thus  in  the  prepara- 
tion of  many  ferments  the  first  step  is  to  produce  an  inert  pre- 
cipitate, such  as  calcium  phosphate,  in  the  juice  or  extract.  Some 
of  the  ferments  act  best  in  an  alkaline,  some  in  an  acid  medium. 
They  all  agree  in  having  an  '  optimum  '  temperature,  which  is  more 
favourable  to  their  action  than  any  other;  a  low  temperature  sus- 
pends their  activity,  and  boiling  abolishes  it  for  ever.  The 
optimum  temperatures  of  the  majority  of  enzymes  lie  between 

•  Ferments  are  usually  designated  by  names  with  the  termination  '  ase,' 
and  indicating  the  kind  of  substances  on  which  they  act,  or  sometimes  their 
source.  Thus  proteases  are  ferments  acting  on  proteins,  amylases  ferments 
acting  on  starch,  etc. 


332  DIGESTION 

37°  and  53°  C ;  the  '  killing  '  temperatures  between  60°  and  75°  C. 
when  they  are  heated  in  solutions,  but  considerably  higher  when 
they  are  heated  dry.  The  action  of  the  digestive  enzymes  is 
hydrolytic — i.e.,  it  is  accompanied  with  the  taking  up  of  the  elements 
of  water  by  the  substance  acted  upon.  The  accumulation  of  the 
products  of  the  action  first  checks  and  then  arrests  it.  In  many 
cases  this  seems  to  be  due  to  combination  of  the  ferment  with  one 
or  other  of  the  end  products,  and  the  consequent  segregation  of 
the  ferment  from  the  reaction  mixture.  The  enzyme  is  not  affected 
indiscriminately  by  any  of  the  end  products.  On  the  contrary, 
their  action  is  curiously  selective.  Thus  the  hydrolysis  of  lactose 
by  lactase  is  retarded  by  galactose,  but  not  by  the  other  end 
product  dextrose.  The  hydrolysis  of  cane-sugar  by  invertase  is 
retarded  by  levulose,  but  not  by  dextrose.  The  splitting  of  the 
dipeptid  (p.  2)  glycyl-/-tyrosin  by  a  ferment  in  the  expressed  juice 
of  3'east-cells  is  greatly  delayed  by  one  of  the  products  (Z-tyrosin), 
but  not  by  the  other  (glycocoll) .  Combination  of  the  ferment  with 
an  end  product  is  not,  however,  the  only  way  in  which  the  reaction 
may  stop  before  the  whole  of  the  substrate,  as  the  substance 
acted  on  by  the  ferment  is  termed,  has  been  changed.  It  has  been 
demonstrated  in  some  cases  that  this  is  due  to  the  action  of  the 
enzymes  being  reversible.  For  example,  lipase  (p.  357)  not  only 
decomposes  the  esters  ethyl  butyrate  or  glycerin  butyrate,  but 
also  builds  them  up  again  from  the  decomposition  products — ethyl 
butyrate  from  ethyl  alcohol  and  butyric  acid,  glycerin  butyrate  from 
glycerin  and  butyric  acid  (Kastle  and  Loevenhart,  Hanriot).  Thus: 
C3H7COOC2H5  +  H20,<ZZ:?'C3H7COOH  +  C2H5OH. 

Ethyl  butyrate.  Water.  Butyric  acid.        Ethyl  alcohol. 

The  action  of  the  enzyme  is  merely  to  accelerate  the  establish- 
ment of  the  proportions  in  which  the  four  bodies  entering  into  the 
reaction  are  in  equilibrium,  and  the  point  of  equilibrium  is  the  same 
whether  we  start  from  one  or  the  other  side  of  the  equation  repre- 
senting the  reaction.  Such  reversible  reactions  in  the  presence  of 
enzymes  seem  to  afford  the  key  to  the  explanation  of  many  of  the 
syntheses  which  are  known  to  occur  in  the  body.  Sometimes  the 
action  is  not  strictly  reversible  in  the  sense  that  precisely  the  original 
material  is  reconstructed,  but  from  the  products  of  the  hydrolysis 
substances  are  synthesized  or  condensed,  which  are  then  incapable 
of  being  split  by  the  ferment.  When  a  concentrated  solution  of 
dextrose  is  acted  on  for  a  long  time  by  yeast  maltase,  a  ferment 
obtained  from  yeast  which  changes  maltose  into  dextrose,  some  of 
the  dextrose  is  reconverted  into  isomaltose  and  dextrin-like  bodies. 
Isomaltose  is  not  again  hydrolysed  by  maltase.  The  ferment 
emulsin  contained  in  almonds  behaves  in  the  converse  way.  It 
hydrolyses  isomaltose  so  as  to  form  dextrose,  and  then  condenses 
dextrose  to  maltose  (Armstrong), 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  333 

Many  of  the  ordinary  substances  of  the  laboratory  will  accelerate 
a  reaction  which  goes  on  slowly  in  their  absence.  These  are  called 
catalysers.  Some  writers  also  speak  of  catalysers  which  retard 
a  reaction  progressing  quickly  in  their  absence.  The  process  by 
which  the  reaction  is  accelerated  (or  retarded)  is  termed  catalysis. 
A  typical  catalyser  can  exert  its  action  when  it  is  present  in  ex- 
ceedingly small  amount  in  comparison  with  the  substance  acted 
upon.  However  it  may  enter  into  the  reaction,  it  does  not  take 
part  in  the  formation  of  the  final  products  nor  contribute  to  the 
energy  changes,  and  for  this  reason  is  often  apparently  unaltered 
at  the  end  of  the  process.  The  catalysers  have  therefore  been 
compared  to  the  lubricants  used  for  machinery  as  contrasted  with 
the  coal  or  other  source  of  energy.  If  it  be  remembered  that  the 
expression  is  a  purely  metaphorical  one,  we  may  say  that  the 
catalyst  oils  the  reaction  so  that  it  shps  on  smoothly  and  swiftly 
to  an  end-point  which  would,  however,  have  been  reached  just  the 
same  in  time.  A  classical  instance  of  catalysis  is  the  inversion 
of  cane-sugar  by  weak  acids,  i.e.,  the  change  of  the  cane-sugar  into 
a  mixture  of  equal  quantities  of  dextrose  and  levulose — a  reaction 
which  may  be  represented  by  the  equation 

C12H22O11  +  HaO= C6H12O8  -I-  CgHiaOfl. 

Cane-sugar.        Water.      Dextrose.  Levulose. 

This  is  a  reaction  which  occurs  also  when  the  sugar  is  simply  dis- 
solved in  water,  but  with  extreme  slowness  at  the  ordinary  tempera- 
ture, although  more  rapidly  at  100°  C.  The  effect  of  the  acid  is 
to  catalyse  the  reaction,  to  markedly  accelerate  it.  The  hydrogen 
ions  of  the  free  acid  are  responsible  for  the  catalysis,  and  they  are 
not  used  up  in  the  process,  for  the  reaction  at  the  end  is  unaltered. 
The  same  action  upon  cane-sugar  is  exerted  by  an  enzyme,  invertase, 
found  in  intestinal  juice,  although  the  laws  governing  the  reaction 
are  somewhat  different.  Reversibility  of  the  reaction  can  be  even 
more  clearly  demonstrated  for  catalysers  than  for  enzymes.  For 
example,  the  condensation  of  acetone  to  diacetone-alcohol,  which 
is  accelerated  by  hydroxyl  ions  (as  by  the  addition  of  sodium 
hydroxide,  ammonia,  etc.),  only  proceeds  to  a  certain  point,  at  which 
equihbrium  is  estabhshed  between  the  proportions  of  acetone  and 
the  condensation  product.  Henceforth  as  much  of  the  latter  is 
decomposed  as  is  condensed.     Thus: 

2CH3.CO.CH3<I=i:^CH3.CO.CH2.C(CH3)20H« 

Acetone.  Acetone  alcohol. 

On  the  other  hand,  the  final  equilibrium  point  need  not  be  the  same 
for  a  catalyser  and  an  enzyme.  For  example,  amyl  butjTate  is 
formed  and  decomposed  according  to  the  equation 

CgHnOH  -t-  C3H7COOH«IZZ:>  C3H7COO.C6Hii  +  HgO. 

Amyl  alcohol.         butyric  acid.  Amyl  bulyrate.  Water. 


334 


DIGESTION 


The  reaction  can  be  accelerated  either  by  a  catalyst — e.g.,  H  ions— 
as  by  addition  of  free  hydrochloric  or  picric  acid,  or  by  pancreas 
hpase.  When  the  concentrations  of  the  reacting  substances  are 
appropriatt^.ly  chosen,  the  same  equilibrium  point  will  be  reached 
from  either  side  of  the  equation — i.e.,  the  same  percentage  of  the 
butyric  acid  will  be  converted  into  the  ester  if  we  start  with  the 
alcohol  and  acid,  as  will  remain  combined  as  ester  if  we  start  with 
the  amyl  butyrate.  But  the  proportion  will  not  be  the  same  when 
the  reaction  is  acclerated  by  H  +  as  when  it  is  accelerated  by  the 
enzyme.  And  although  it  is  probable  that  there  is  no  fundamental 
difference  between  the  action  of  the  digestive  enzymes  and  that  of 
the  inorganic  catalysers,  it  is  much  too  early  to  dogmatize. 

Not  even  the  markedly  specific  action  of  the  digestive  ferments 
can  be  considered  an  essential  distinction.     It  is  true  that  invertase 
will  act  upon  dextrose,  and  not  at  all  upon  maltose  or  lactase. 
But  there  are  other  sugars,  e.g.,  rafiinose,  a  trisaccharide  with  the 
formula  CigHgaOjg,  obtained  from  beet-sugar  residues,  which  it  will 
hydrolyse.     Rafhnose  is  made  up  of  one  molecule  each  of  dextrose, 
levulose,  and  galactose.     On  heating  with  dilute  acids,  it  is  decom- 
posed into  these  substances.     Invertase,  however,  only  splits  off 
the  levulose  molecule,  leaving  a  disaccharide  isomeric,  but  not 
identical  with  lactose.     Similarly  lactase,  which  is  without  action 
upon  cane-sugar  or  maltose,  will  hydrolyse  the  S-galactosides,  and 
maltase,  inert  as  regards  cane-sugar  or  lactose,  will  hydrolyse  the 
a-glucosides.     On  the  other  hand,  emulsin  decomposes  the  /3-gluco- 
sides,  to  which  group  most  of  the  natural  glucosides  belong,  as  well 
as  the  /3-galactosides  and  lactose.      From  rafhnose  emulsin  splits 
off  galactose,  leaving  cane-sugar.     Since  the  a  and  /3  compounds 
are  isomeric,  and  differ  not  in  their  composition  but  in  their  struc- 
ture, it  has  been  concluded  that  the  structure  of  the  molecule  of 
a  substance  must  be  related  to  the  structure  of  the  enzyme  which 
can  act  on  it,  in  some  such  way  as  a  lock  is  related  to  its  proper  key. 
Thus  the  key  lactase  fits  in  the  lock  lactose,  but  not  in  the  lock 
dextrose  or  the  lo:k  maltose.     Although  the  same  specificity  is 
not  to  be  observed  in  the  action  of  catalysers  as  in  the  action  of 
enzymes,  it  is  not  difficult  to  find  many  instances  in  which  inorganic 
substances  show  a  marked  hmitation  of  their  catalytic  effects  to 
particular  reactions.     Thus  hydriodic  acid  is  slowly  oxidized  in 
presence  of  hydrogen  peroxide,  with  formation  of  iodine  and  water. 
This  reaction  is  accelerated  by  the  addition  of  many  substances, 
e.g.,  tungstic  acid.     But  tungstic  acid  has  no  catalytic  effect  on  the 
oxidation  of  hydriodic  acid  by  bromic  acid. 

The  existence  of  an  optimum  temperature  for  ferment  action, 
above  which  it  rapidly  decreases,  and  eventually  comes  to  a  com- 
plete stop,  is  also  in  all  probability  only  a  superficial  distinction 
between  enzymes  and  catalysers.     For  enzymes  are  easily  altered, 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  335 

or  even  destroyed,  at  temperatures  which  very  likely  would  favour 
their  action  were  they  as  thermostable  as  the  majority  of  catalysing 
agents.  And  inorganic  catalysts  are  known  which  also  show  the 
phenomenon  of  an  optimum  temperature  depending  on  changes 
produced  in  their  physical  condition  when  the  temperature  is 
raised  above  this  point.  Thus  a  colloidal  solution  (or  '  sol,'  as  it  is 
called)  of  platinum,  prepared  by  passing  electric  sparks  between 
two  platinum  electrodes  immersed  in  distilled  water,  and  containing 
the  metal  in  the  form  of  ultra-microscopic  particles,  acts  as  a  cata- 
lyser  of  a  number  of  reactions.  As  the  temperature  is  increased 
up  to  a  certain  '  optimum,'  the  velocity  of  the  catalysed  reaction 
is  increased.  But  beyond  this,  as  the  boiling-point  is  approached, 
the  colloidal  platinum  is  precipitated,  and  ceases  to  influence  the 
reaction. 

As  to  the  manner  in  which  an  enzyme  increases  the  velocity  of  its 
appropriate  reaction,  it  is  not  easy  to  make  any  very  positive  statement. 
Several  possibilities  arc  recognized,  of  which  two  have  been  especially 
discussed,  (i)  The  existence  of  the  enzyme  in  colloidal  solution  may 
be  important.  It  is  characteristic  of  colloidal  solutions,  in  which  the 
dissolved  substance  is  present  in  the  form  of  extremely  fine  particles, 
that  the  total  surface  of  the  particles  is  very  great  in  proportion  to 
the  mass  of  the  substance  in  solution.  Thus,  a  sphere  of  about  the 
same  volume  as  the  eyeball,  with  a  diameter  of,  say,  2  centimetres, 
would  have  a  surface  of  I2"5  square  centimetres.  If  this  material  were 
subdivided  into  spheres  of  about  the  same  volume  as  a  leucocyte,  with 
a  diameter  of,  say,  10  /x,  it  would  form  eight  thousand  million  of  these 
spheres,  with  a  total  surface  of  over  2J  square  metres.  If  the  small 
spheres  were  further  subdivided  into  spherical  particles,  with  a  diameter 

only  the  thousandth  part  of  that  of  a  leucocyte,  say  -^,  each  would 

form  a  thousand  million  of  these  particles,  and  the  total  surface  of  all 
the  particles  would  be  about  2,500  square  metres. 

Now,  it  is  known  that  the  intensity  of  action  of  some  of  the  inorganic 
catalyscrs  is  proportional  to  the  surface  exposed.  For  example, 
hydrogen  peroxide,  if  left  to  itself,  is  slowly  decomposed  into  water  and 
oxygen.  The  addition  of  finely  divided  platinum,  in  the  form  of 
platinum  black,  greatly  hastens  the  decomposition,  and  the  ox>'gen 
bubbles  off.  The  colloidal  platinum  sol  is  still  more  effective.  The 
nature  of  the  surface  effect  is  not  entirely  clear.  One  factor  has  been 
thought  to  be  an  increase  in  the  concentration  of  dissolved  substances 
or  condensation  of  gases  at  the  surface,  and  tlie  better  opportunity 
for  mutual  action  thus  afforded  to  the  ferment  and  the  substrate. 
The  great  extension  of  the  surface  cannot  be  the  only  factor  in  the 
catalysis;  otherwise  any  fine  powder  or  suspension  would  have  a  cata- 
lytic action.  But  kaolin,  or  fine  sand,  or  colloidal  solutions  of  ordinary 
proteins  or  gelatin,  have  little,  if  any,  effect  on  the  decomposition  of 
hydrogen  peroxide. 

(2)  Enzymes  may  produce  their  effects  by  contributing  to  the  for- 
mation of  bodies  intermediate  between  the  substrate  and  the  end- 
products.  If  the  time  required  for  the  formation  of  a  given  quantity 
of  the  intennediate  compound  and  the  time  required  for  the  decom- 
position of  this  compound  into  the  final  products  of  the  ferment  action 
are  in  sum  less  than  the  time  required  for  the  direct  change  of  the 


336 


DIGESTION 


substrate  into  the  end-products,  the  enzyme  will  clearly  act  as  a  cata- 
lyser  of  the  reaction.  It  has  been  shown  that  in  the  case  of  certain 
inorganic  catalysers  this  does  occur.  Thus,  in  the  oxidation  of  hydriodic 
acid  by  hydrogen  peroxide,  which  has  been  already  referred  to, 
molybdic  acid  has  the  power  of  acting  as  a  catalyser.  It  has  been  proved 
that  the  reaction  occurs  in  two  stages,  permolybdic  acid  being  first 
formed  by  the  action  of  the  peroxide  on  molybdic  acid.  The  permol- 
ybdic acid  then  acts  on  hydriodic  acid,  producing  iodine  and  water, 
and  being  itself  reduced  again  to  molybdic  acid,  which  therefore  comes 
out  at  the  end  of  the  reaction  unchanged.  The  velocity  of  the  double 
reaction  is  much  greater  than  that  of  the  direct  oxidation  of  hj'driodic 
acid  by  hydrogen  peroxide. 

.  There  is  evidence  that  the  ferment  actually  combines  with  the  sub- 
strate, the  combination  then  breaking  up  to  form  the  end-products. 
For  instance,  it  has  been  shown  that  the  amount  of  lactose  hydrolysed 
by  lactase  in  a  given  time,  when  the  ferment  is  present  in  very  small 
quantity  in  comparison  with  the  substrate,  is  proportional  to  the  con- 
centration of  the  ferment,  and  independent  of  the  concentration  of 
the  lactose.  Also  with  a  given  small  concentration  of  ferment  the 
amount  of  lactose  hydrolysed  is  at  first  the  same  for  successive  equal 
intervals  of  time.  These  facts  can  only  be  explained  by  the  assump- 
tion that  the  ferment  first  combines  with  a  portion  of  the  substrate,  the 
rest  of  which  remains  inactive  as  regards  the  reaction,  and  that  this 
combination  then  takes  up  water  and  decomposes  into  the  end- 
products,  in  this  case  dextrose  and  galactose,  setting  free  the  ferment 
to  combine  with  another  portion  of  the  substrate. 

The  Quantitative  Estimation  of  Ferment  Action. — Since  we  have  as  yet 
no  certain  method  of  freeing  the  digestive  ferments  from  impurities, 
our  only  quantitative  test  is  their  digestive  activity.  And  since  a  very 
small  quantity  of  ferment  can  act  upon  a  practically  indefinite  amount 
of  material  if  allowed  sufficient  time,  we  can  only  make  comparisons 
when  the  time  of  digestion  and  all  other  conditions  are  the  same.  If 
we  find  that  a  given  quantity  of  one  gastric  extract,  acting  on  a  given 
weight  of  fibrin,  dissolves  it  in  half  the  time  required  by  an  equal 
amount  of  another  gastric  extract,  or  dissolves  twice  as  much  of  it  in  a 
given  time,  we  conclude  that  the  digestive  activity  of  the  pepsin  is  twice 
as  great  in  the  first  extract  as  in  the  second.  But  this  does  not  permit 
us  to  say  that  the  one  contains  twice  as  much  pepsin  as  the  other.  For 
it  has  been  found  that  the  amount  of  digestion  in  a  given  time  is  not 
directly  proportional  to  the  quantity  of  ferment  present,  but  to  the 
square  root  of  the  quantity  of  ferment  (Schiitz's  law).  This  law  was 
deduced  by  Schiitz  for  pepsin,  but  is  said  to  hold  also  for  trypsin, 
steapsin,  and  ptyalin  (Pawlow,  Vernon).  To  determine  the  amount  of 
proteolysis  the  nitrogen  of  the  protein  which  has  gone  into  solution  may 
be  estimated  (p.  514).  The  following  table  shows  the  results  of  one 
experiment : 


Pepsin  Solution  used 
in  C.C. 

Digested  Nitrogen  in  Grammes. 

Found. 

Calculated. 

I 

4 

9 

16 

00230 
0*0427 
00686 

o-o88g 

0*0223 
0*0446 

o'o669 
0*0892 

THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  337 

Or  a  piece  of  a  glass  capillary-tube  filled  with  heat-coagulated  egg-white 
may  be  cut  off  and  placed  in  the  digestive  mixture  (Mctt's  tubes).  At 
the  end  of  the  period  of  digestion  the  length  of  the  piece  of  tube  and 
that  of  the  undigested  remnant  of  the  column  of  coagulated  protein 
are  measured  with  a  millimetre  scale  under  a  low-power  microscope. 
The  difference  gives  the  length  of  the  column  digested.  If  i  c.c.  of 
gastric  juice  caused  in  a  given  time  digestion  of  2  mm.  of  the  egg-white, 
4  c.c.  of  the  same  juice  would  digest  in  the  same  time  and  under  identical 
conditions  about  4  mm.,  and  9  c.c.  about  6  mm.  As  a  test  of  the 
activity  of  a  diastatic  ferment,  we  take  the  amount  of  sugar  formed  in 
a  given  time  in  a  given  quantity  of  a  standard  starch  solution.  To 
determine  the  activity  of  a  liquid,  say,  the  pancreatic  juice,  as  regards 
fat-splitting  ferment,  the  aciditv  of  the  emulsion  formed  by  the  juice 
and  fat  after  standing  for  a  definite  time  at  a  given  temperature  (with 
occasional  shaking)  can  be  estimated  by  titration  with  baryta  solution. 

In  addition  to  the  ferments  of  the  digestive  juices  which  act  extra- 
cellularly  in  the  lumen  of  the  alimentary  canal,  and  those  which 
do  their  work  intracellularly  in  its  walls,  micro-organisms  are 
present  in  the  gut,  and  even  in  normal  digestion  contribute  to  the 
changes  brought  about  in  the  food ;  while  under  abnormal  conditions 
they  may  awaken  into  troublesome,  and  even  dangerous,  activity. 
It  is  now  known  that  these  act  by  producing  intracellular  enzymes. 

It  may  be  noted  here,  although  the  subject  must  be  again  referred 
to  (p.  384),  that  specific  substances  capable  of  inhibiting  the  action 
of  ferments  exist.  Some  of  these  antiferments  are  normally  present 
in  the  body — an  antitrypsin,  for  instance,  in  normal  blood-serum. 
Numerous  antiferments  may  be  artificially  obtained  by  immunizing 
animals  with  the  original  ferments.  Thus  an  antihpase  is  found 
in  the  serum  of  rabbits  after  injection  of  pancreatic  lipase,  and  an 
antiemulsin  after  injection  of  emulsin.  Injection  of  rennin  causes 
the  formation  of  antirennin,  which  can  be  demonstrated  in  the 
blood-serum  and  milk  of  the  immunized  animal.  Besides  the  anti- 
ferments, bodies,  sometimes  spoken  of  as  '  co-enzymes,'  are  known 
which  aid  the  action  of  certain  enzymes,  not  in  the  general  way 
in  which,  for  instance,  increase  of  temperature  up  to  the  optimum 
does,  but  in  some  quite  special  manner.  Thus,  as  we  shall  see, 
bile  salts  greatly  facilitate  the  fat-splitting  action  of  hpase.  This 
co-operation  is  not  to  be  confounded  with  the  activation  of  the 
proferment  or  zymogen  which  in  many  cases  represents  the  inactive 
form  of  the  enzyme,  while  it  is  still  within  the  secreting  cells.  For, 
once  activated,  the  fully  formed  enzyme  cannot  be  made  to  revert 
to  the  zymogen  stage.  For  example,  the  active  trypsin  of  the 
pancreatic  juice  cannot  be  changed  into  inactive  trypsinogen, 
whereas  substances  which  simply  co-operate  or  co-act  with  enzymes 
leave  the  latter  unaltered  when  they  arc  removed.  Thus  lipase  does 
not  preserve  the  increased  activity  conferred  upon  it  by  bile  salts 
when  the  bile  salts  are  again  separated  from  the  digestive  mixture. 

It  is  now  necessary  to  consider  in  det  lil  the  nature  of  the  variou? 


338  DIGESTION 

juices  jdelded  by  the  digestive  glands,  and  the  mechanism  of  theii 
secretion.  Since  it  is  along  the  digestive  tract  that  glandular  action 
is  seen  on  the  greatest  scale,  this  discussion  will  practically  embrace 
the  nature  of  secretion  in  general.  And  here  it  may  be  well  to  say 
that,  although  in  describing  digestion  it  is  necessary  to  break  it  up 
into  sections,  a  true  view  is  only  got  when  we  look  upon  it  as  a 
single,  though  complex,  process,  one  part  of  which  fits  into  the  other 
from  beginning  to  end.  It  is,  indeed,  the  business  of  the  physiologist, 
wherever  it  is  possible  to  insert  a  cannula  into  a  duct  and  to  drain 
off  an  unmixed  secretion,  to  investigate  the  properties  of  each  juice 
upon  its  own  basis;  but  it  must  not  be  forgotten  that  in  the  body 
digestion  is  the  joint  result  of  the  chemical  work  of  five  or  six 
secretions,  the  greater  number  of  which  are  actually  mixed  together 
in  the  alimentary  canal,  and  of  the  mechanical  work  of  the  gastro- 
intestinal walls. 

Saliva. — The  sahva  of  the  mouth  is  a  mixture  of  the  secretions 
of  three  large  glands  on  each  side,  and  of  many  small  ones.  The 
large  glands  are  the  parotid,  which  opens  by  Stenson's  duct  opposite 
the  secofid  upper  molar  tooth;  the  submaxillary,  which  opens  by 
Wharton's  duct  under  the  tongue;  and  the  sublingual,  opening  by 
a  number  of  ducts  near  and  into  Wharton's.  The  small  glands  are 
scattered  over  the  sides,  floor,  and  roof  of  the  mouth,  and  over  the 
tongue. 

Two  types  of  salivary  glands,  the  serous  or  albuminous  and  the 
mucous,  are  distinguished  by  structural  characters  and  by  the 
nature  of  their  secretion;  and  the  distinction  has  been  extended 
to  other  glands.  The  parotid  of  many,  if  not  all,  mammals  is  a 
purely  serous  gland;  it  secretes  a  watery  juice  with  a  general  re- 
semblance in  composition  to  dilute  blood-serum.  The  submaxillary 
of  the  dog  and  cat  is  a  typical  mucous  gland ;  its  secretion  is  viscid, 
and  contains  mucin.  The  submaxillary  gland  of  man  is  a  mixed 
gland;  mucous  and  serous  alveoli,  and  even  mucous  and  serous 
cells,  are  intermingled  in  it.  The  submaxillary  of  the  rabbit  is 
purely  serous.  The  sublingual  is,  in  general,  a  mixed  gland,  but 
with  far  more  mucous  than  serous  alveoli.  Some  of  the  small 
glands  are  serous,  others  mucous  in  type. 

The  mixed  saliva  of  man  is  a  somewhat  viscous,  colourless  liquid 
of  low  specific  gravity  (1002  to  1008,  average  about  1005),  alkaline 
to  litmus,  acid  to  phenolphthalein,  but  when  tested  by  the  electrical 
method  (p.  24)  almost  neutral.  Besides  water  and  salts,  it  contains 
mucin  (entirely  from  the  submaxillary,  the  subhngual  and  the 
small  mucous  glands  of  the  mouth),  to  which  its  viscidity  is  due, 
traces  of  serum-albumin  and  serum-globulin  (chiefly  from  the 
parotid),  and  a  ferment,  which  hydrolys;'s  starch,  and  therefore 
belongs  to  the  group  of  amlyases  or  diastases.  It  difiers  somewhat 
from  the  amylase  of  pancreatic  juice.     But  the  small  differences 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES 


339 


tones 
no-acids 

ctose 
lose 

,  guanylic 

2 

a. 

thin 

ygen 
ation 

1 

o 

« 

.  and 
and 
ids 
and 
and 

ds 

ids,  ' 
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acid 
thin 

d  ox 
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S 

Maltose 

Proteoses 

Peptones 

Amino-ac 

Dextrose 

Dextrose 

Dextrose 

Fatty  aci 

Dextrose 
Amino-ac 
Simpler  a 

acid) 
Urea  and 
Salicylic  ; 
Hypoxan 
Xanthin 
Trypsin 
Water  an 
Coloured 

Acetic  ac 
Xanthin 
Uric  acid 

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Starch 
Protein 

Proteos 
Lactose 
Cane-su 
Maltose 
Neutral 

Glycoge 
Protein; 
Nucleic 

Arginin 
Salic  yl  i 
Adenin 
Guanin 
Trj^psin 
Hydrog 
Phenols 
amin( 

.S  o  y^'M 

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pancreati 
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issue,  etc. 

!  generally 
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;n,  etc. 
spleen 
issues 
as,  liver,  s 
as,  thymu 
nal  juice 
issues 
s  tissues 

o 
o 

s  tissues 
;      juice, 
:,  etc. 

Saliv'a, 
Gastric 
Pancre 
Intesti 

Saliva, 
Pancre 
fat  t 
Liver 
Tissues 
Intesti: 

splee 
Liver, 
Most  ti 
Pancre 
Pancre 
Intesti 
.Most  t: 
Variou 

Liver, 

Variou 

Gastric 

juice 

ucrase    - 

ymes 
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1    1    1    1    1    1    1 

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1       1       1       1       1      iH      1       1             CJ    d  TJ 

rginase 

Ideh^'dasc 

denase 

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nterokinase 

atalase 

henoloxydas 

U     1 

V 

c 

/  Amylase 
Pepsin 
Trypsin 
Erepsin 
Lactase 
Invertase  o 
Maltase 
Lipase 

Glycogenasi 
Autoh-tic  e 
Nuclein  aci 

2°    § 
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ri 
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s:5  n" 

Ox 

dizi 

enzy: 

340  DIGESTION 

usually  found  between  ferments  of  the  same  kind  derived  from 
different  sources  may  be  due  to  the  presence  of  other  substances, 
and  do  not  necessarily  indicate  that  the  ferments  are  distinct.  For 
the  present  it  may  be  assumed  that  the  amylase  of  saliva  is  the 
same  ferment  encountered  in  the  pancreatic  juice,  and  in  many, 
or  all,  of  the  tissues.  An  oxydase  or  oxidizing  ferment  is  also 
present  in  saliva.  The  salts  are  calcium  carbonate  and  phosphate 
(often  deposited  as  '  tartar  '  around  the  teeth,  occasionally  as 
sahvary  calculi  in  the  glands  and  ducts),  sodium  bicarbonate, 
sodium  and  potassium  chloride,  and  almost  always  a  trace  of  sul- 
phocyanide  of  potassium,  detected  by  the  red  colour  which  it  strikes 
with  ferric  chloride.*  The  total  solids  amount  only  to  five  or  six 
parts  in  the  thousand.  A  great  deal  of  carbon  dioxide  can  be 
pumped  out  from  saliva,  as  much  as  60  to  70  c.c.  from  100  c.c. 
of  the  secretion — i.e.,  more  than  can  be  obtained  from  venous  blood. 
Only  a  small  proportion  of  this  is  in  solution,  the  rest  existing  as 
carbonates.  Oxygen  is  also  present  even  in  saliva  which  has  not 
come  into  contact  with  the  air,  and,  indeed,  in  somewhat  greater 
quantity  than  in  serum  (about  0*6  volume  per  cent,  in  dog's  saUva). 
Under  the  microscope  epithelial  scales,  dead  and  swollen  leucocytes 
(the  so-called  salivary  corpuscles),  bacteria,  and  portions  of  food, 
may  be  found.  All  these  things  are  as  accidental  as  the  last — 
they  are  mere  flotsam  and  jetsam,  washed  by  the  sahva  from  the 
inside  of  the  mouth.  But  greater  significance  attaches  to  certain 
peculiar  bodies,  either  spherical  or  of  irregular  shape,  that  are  seen 
in  the  viscid  submaxillary  saliva  of  the  dog  or  cat.  They  appear 
to  be  masses  of  secreted  material.  The  quantity  of  saliva  secreted 
in  the  twenty-four  hours  varies  a  good  deal.  On  an  average  it  is 
from  I  to  2  litres  (Practical  Exercises,  p.  448). 

Besides  its  functions  of  dissolving  sapid  substances,  and  so  allow- 
ing them  to  excite  sensations  of  taste,  of  moistening  the  food  for 
deglutition  and  the  mouth  for  speech,  and  of  cleansing  the  teeth 
after  a  meal,  saliva,  in  virtue  of  its  ferment,  amylase,  has  the  power 
of  digesting  starch  and  converting  it  into  the  disaccharide  maltose, 
a  reducing  sugar  (C12H22O11).  In  man  the  secretion  of  any  of  the 
three  great  salivary  glands  has  this  power,  although  that  of  the 
parotid  is  most  active.  In  the  dog,  on  the  other  hand,  parotid  saUva 
has  little  action  on  starch,  and  submaxillary  none  at  all;  while  in 
animals  like  the  rat  and  the  rabbit  the  parotid  secretion  is  highly 
active.  In  the  horse,  sheep,  and  ox,  the  saliva  secreted  by  all  the 
glands  seems  equally  inert. 

When  starch  is  boiled,  the  granules  are  ruptured,  and  the  starch 

*  In  100  students  the  saliva  only  once  failed  to  give  the  reaction,  and  in 
this  individual  a  trace  of  sulphocyanide  was  present  3  days  later.  It  is  absent 
from  the  saliva  of  many  animals.  In  25  dogs  submaxillary  saliva  obtained 
by  stimulation  of  the  chorda  tympani  only  once  gave  the  ferric  chloride 
reaction,  and  then  faintly. 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  341 

passes  into  colloidal  solution,  yielding  an  opalescent  liquid.  If  a 
little  saliva  be  added  to  some  boiled  starch  solution  which  is  free 
from  sugar,  and  the  mixture  be  set  to  digest  at  a  suitable  temperature 
(say  40°  C),  the  solution  in  a  very  short  time  loses  its  opalescence 
and  becomes  clear.  It  still,  however,  gives  the  blue  reaction  with 
iodine;  and  Trommer's  test  (p.  10)  shows  that  no  sugar  has  as  yet 
been  formed.  Later  on  the  iodine  reaction  passes  gradually  through 
violet  into  red;  and  finally  iodine  causes  no  colour  change  at  all, 
while  maltose  is  found  in  large  amount,  along  wnth  some  isomaltose 
(p.  332),  a  sugar  having  the  same  formula  as  maltose,  but  differing 
from  it  in  the  melting-point  of  the  crystalline  compound  formed  by 
it  with  phenyl-hydrazine  (p.  517).  Traces  of  dextrose,  a  sugar 
which  rotates  the  plane  of  polarization  less  than  maltose,  but  has 
greater  reducing  power,  may  be  found  among  the  end-products 
when  the  digestion  is  conducted  in  vitro.  It  is  probable  that  this 
is  produced  from  the  maltose  by  another  enzyme  (maltase),  present 
in  smill  amount  in  saUva.  In  any  case  it  is  well  known  that  mal- 
tose may  be  a  stage  in  the  hydrolysis  of  starch  to  dextrose,  and  can 
be  detected  among  the  intermediate  products  when  the  starch  is 
acted  on  by  dilute  acid  under  conditions  which  permit  a  gradual 
decomposition  of  the  fragments  into  which  the  polysaccharide 
molecule  is  successively  split.  But  the  observation  has  also  been 
made  that  the  saUva  itself  (in  the  cat)  may  contain  a  trace  of  dex- 
trose (Carlson). 

The  red  colour  indicates  the  presence  of  a  kind,  or  a  group,  of 
dextrins  sometimes  called  erythrodextrin,  because  of  this  colour 
reaction;  the  violet  colour  shows  that  at  first  this  is  still  mixed  with 
some  unchanged  starch.  Soon  the  dextrins  which  give  the  red  colour 
disappear,  and  are  succeeded  by  other  dextrins,  which  give  no  colour 
with  iodine,  and  are  therefore  called  achrodextrins.  These  are 
partly,  but  in  artificial  digestion  never  completely,  converted  into 
maltose,  and  can  always  at  the  end  be  precipitated  in  greater  or 
less  amount  by  the  addition  of  alcohol  to  the  liquid.  It  is  probable 
that  a  whole  series  of  dextrins  is  formed  during  the  digestion  of 
starch.  But  little  is  known  of  their  chemical  nature.  Recently, 
however,  some  of  these  intermediate  bodies  have  been  obtained 
in  crystalline  form.  One  of  these  appears  to  be  a  hexa-amylose — 
i.e.,  it  consists  of  six  QHioOg  groups,  and  would  therefore  be 
capable  of  yielding,  on  the  assumption  of  water,  three  molecules 
of  maltose  or  six  of  dextrose.  This  is  accordingly  a  relatively 
small  fragment  of  the  big  original  molecule  of  starch.  When  the 
sugar  is  removed  as  it  is  formed,  as  is  approximately  the  case  when 
the  digestion  is  performed  in  a  dialyser,  the  residue  of  unchanged 
dextrin  is  less  than  when  the  sugar  is  allowed  to  accumulate  (Lea). 
In  ordinary  artificial  digestion,  for  instance,  under  the  most  favour- 
able circumstances  at  least  12  to  15  per  cent,  of  the  starch  is  left 


342  DIGESTION 

as  dextrin;  in  dialyser  digestions  the  residue  of  dextrin  may  be 
little  more  than  4  per  cent.  This  goes  far  to  explain  the  complete 
digestion  of  starch  which  takes  place  in  the  ahmentary  canal,  a 
digestion  so  exhaustive  that,  although  dextrins  may  be  found  in 
the  stomach  after  a  starchy  meal,  they  do  not  occur  in  the  intestine, 
or  only  in  minute  traces.  Here  the  am54olytic  ferment  of  the 
pancreatic  juice,  which  is  essentially  the  same  in  its  action  as  the 
amylase  of  sahva,  only  more  powerful,  must  effect  a  very  complete 
conversion  of  the  starch  molecules  accessible  to  its  attack.  It  is 
not  inconsistent  with  this,  that  unchanged  starch  granules  may 
sometimes  be  excreted  in  the  faeces,  especially  when  imbedded  in 
raw  vegetable  structures.  For  it  may  be  easily  shown  that  un- 
boiled starch  is  digested  by  amylase  with  far  greater  difficulty  than 
boiled  starch,  an  illustration  of  the  important  part  played  by 
cooking  in  the  preparation  of  the  food  for  digestion. 

It  is  a  notable  fact  that  amylases,  also  called  diastases,  are  not 
confined  to  the  animal  body,  but  are  widely  distributed  in  plants. 

The  polysaccharide  starch  forms  the  great  reserve  of  carbohydrate 
material  in  plant  nutrition,  and  is  mobilized  for  the  use  of  the 
vegetable  cells  by  being  hydrolysed  to  simple  sugars  under  the  in- 
fluence of  these  enzymes,  just  as  the  polysaccharide  glycogen,  the 
great  carbohydrate  reserve  of  animal  nutrition  (p.  525),  is  mobihzed 
in  the  form  of  dextrose  under  the  influence  of  the  diastase  of  the 
liver.  A  diastase,  which  is  present  in  all  sprouting  seeds,  and 
may  be  readily  extracted  by  water  from  malt,  forms  dextrin  and 
maltose  from  starch.  The  optimum  temp>erature  of  malt  diastase, 
however,  is  about  55°  C,  while  that  of  ptyaUn  is  about  40"  C. 

While  a  neutral  or  weakly  alkaline  reaction  is  not  unfavourable 
to  sahvary  digestion,  it  goes  on  best  in  a  slightly  acid  medium. 
It  has  been  shown  that  the  activity  of  ptyaUn  on  starch,  both 
having  been  previously  dialysed  to  get  rid  as  far  as  possible  of  salts, 
is  increased  by  the  addition  of  very  small  amounts  of  acids  and  of 
the  neutral  salts  of  strong  monobasic  acids.  The  action  is  decreased 
by  larger  amounts  of  acid  (0-0007  to  0-0012  per  cent,  of  hydrochloric 
acid)  and  by  neutral  salts  of  weak  acids.  An  acidity  equal  to  that 
of  a  o-i  per  cent,  solution  of  hydrochloric  acid  stops  sahvary 
digestion  completely,  although  the  ferment  is  still  for  a  time 
able  to  act  when  the  acidity  is  sufficiently  reduced.  Strong  acids 
or  alkahes  permanently  destroy  it.  These  facts  indicate  that  in 
the  mouth,  where  the  reaction  is  weakly  alkaline,  the  conditions 
are  comparatively  favourable  to  the  action  of  the  ptyalin.  They 
are  still  more  favourable  in  the  stomach  for  some  time  after  the 
beginning  of  a  meal,  while  the  reaction  is  yet  weakly  acid.  It  has 
been  observed  that  (in  cats)  salivary  digestion  may  go  on  for  an 
hour  or  more  in  the  cardiac  end  of  the  stomach,  since  free  hydro- 
chloric acid  does  not  appear  here  before  that  time.     Since  the  con- 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  343 

tents  of  the  cardiac  end  are  not  freely  intermixed  with  those  of  the 
pyloric  end,  a  greater  proportion  of  sugar  is  found  in  the  former, 
and  the  difference  is  more  marked  with  sohd  than  with  hquid  food 
(Cannon  and  Day).  But  during  the  greater  part  of  gastric  digestion 
the  degree  of  acidity  is  such  that  the  ptyaHn  must  be  hindered. 
Although  the  food  stays  but  a  short  time  in  the  mouth,  there  is  no 
doubt  that,  in  man  at  least,  some  of  the  starch  is  there  changed  into 
sugar  (p.  350).  But  this  is  not  the  case  in  all  animals.  Something 
depends  on  the  amylolytic  activity  of  the  saliva,  and  something 
upon  the  form  in  which  the  starchy  food  is  taken,  whether  it  is 
cooked  or  raw,  enclosed  in  vegetable  fibres,  or  exposed  to  free  ad- 
mixture with  the  secretions  of  the  mouth. 

The  fact  already  mentioned  that  hydrolytic  changes  of  the  same 
nature  as  those  produced  by  enzymes  can  be  brought  about  in  other 
ways  holds  good  for  the  salivary  amylase.  If  starch  is  heated  for 
a  time  with  dilute  hydrochloric  or  sulphuric  acid,  it  is  changed 
first  into  dextrin,  and  then  into  a  sugar,  which,  however,  is  not 
the  disaccharide  maltose,  but  the  monosaccharide  dextrose — that 
is  to  say,  the  hydrolysis  with  acid  proceeds  a  step  farther  than  the 
hydrolysis  in  the  presence  of  ptyalin.  If  maltose  is  treated  with 
acid  in  the  same  way,  it  is  also  changed  into  dextrose.  When 
glycogen  (p.  i)  is  boiled  with  dilute  oxalic  acid  at  a  pressure  of  three 
atmospheres,  isomaltose  and  dextrose  are  formed  (Cremer).  Facts 
already  mentioned,  and  others  to  be  cited  later  on,  show  that  the 
action  of  the  other  digestive  ferments  can  also  be  imitated  by 
purely  artificial  means.  Indeed,  we  may  say  that  the  ferments 
accomplish  at  a  comparatively  low  temperature  what  can  be  done 
in  the  laboratory  at  a  higher  temperature,  and  by  the  aid  of  what 
may  be  called  more  violent  methods. 

-Gastric  Juice. — The  Abbe  Spallanzani,  although  not,  perhaps, 
the  first  to  recognize,  was  the  first  to  study  systematically,  the 
chemical  powers  of  the  gastric  juice,  but  it  was  by  the  careful 
and  convincing  experiments  of  Beaumont  that  the  foundation  of 
our  exact  knowledge  of  its  composition  and  action  was  laid. 

It  is  difficult  to  sp^ak  without  enthusiasm  of  the  work  of  Beaumont, 
if  we  consider  the  difficulties  under  which  it  was  carr'ed  on.  An  army 
surgeon  stationed  in  a  lonely  post  in  the  wiklcmcss  that  was  then 
called  the  territory  of  Michigan,  a  thousand  miles  from  a  University, 
and  four  thousand  irom  anything  like  a  physiok>gical  laboratory,  he 
was  accidentally  called  upon  to  treat  a  gun-shot  wound  of  the  stomach 
in  a  Canadian  voyageur,  Alexis  St.  Martin.  When  the  wound  healed, 
a  permanent  fistulous  opening  was  left,  by  means  of  which  food  could 
be  introduced  into  the  stomach  and  gastric  juiie  obtained  from  it. 
Beaumont  at  once  perceived  the  possibilities  of  such  a  case  for  physio- 
logical research,  and  Icgan  a  series  of  experiments  on  dig  stion.  After 
a  while,  St.  Martin,  with  the  wandering  spirit  of  the  voyag.ur,  returned 
to  Canada  without  Dr.  Beaumont's  consent  and  in  his  absence. 
Beaumont  traced  him,  with  great  difficulty,  by  the  help  of  tlic  agents 
of  a  fur-trading  company,  induced  him  to  come  back,  ])rovidcd  for  his 


344  DIGESTION 

family  as  well  as  for  himself,  and  proceeded  with  his  investigations. 
A  second  time  St.  Martin  went  back  to  his  native  country,  and  a  second 
time  the  zealous  investigator  of  the  gastric  juice,  at  heavy  expense, 
secured  his  return.  And  although  his  experiments  were  necessarily  less 
exact  than  would  be  permissible  in  a  modem  research,  the  modest  book 
in  which  he  published  his  results  is  still  counted  among  the  classics  of 
physiology.  The  production  of  artificial  fistulas  in  animals,  a  method 
that  has  since  proved  so  fruitful,  was  first  suggested  by  his  work. 

Gastric  juice  when  obtained  pure,  as  it  can  be  from  an  acci- 
dental fistula  in  man,  or,  better,  by  giving  a  dog  with  an  oesophageal 
as  well  as  a  gastric  fistula  a  '  sham-meal '  (p.  396),  is  a  clear,  thin, 
colourless  liquid  of  low  specific  gravity  (in  the  dog  1003  to  1006) 
and  distinctly  acid  reaction.  The  total  solids  average  about 
5  parts  per  thousand,  of  which  the  ash  (chiefly  sodium  and  potas- 
sium chloride,  with  small  quantities  of  calcium  and  magnesium 
phosphate)  represents  about  a  fourth,  and  heat-coagulable  sub- 
stances (proteins,  nucleoprotein)  about  .a  third.  None  of  these  has 
any  special  importance  in  digestion.  Of  quite  a  different  significance 
are  the  three  ferments  present:  pepsin,  which  changes  proteins 
into  peptones;  rennin,  which  curdles  milk;  and  a  fat-splitting  fer- 
ment or  lipase  which,  under  certain  conditions  at  least,  splits 
up  emulsified  neutral  fats — e.g.,  the  fat  of  milk — -into  the 
alcohol  (glycerin)  and  the  fatty  acids  linked  with  it,  but  has  so 
little  action  upon  non-emulsified  fat,  that  when  this  is  taken  into 
the  stomach,  it  eventually  passes  into  the  duodenum  practically 
unchanged.  The  acidity  is  due  to  free  hydrochloric  acid,  the  other 
important  constituent  of  the  juice.  In  the  dog  the  proportion  of 
this  acid  varies  from  0-46  to  0-58  per  cent.  In  such  analyses  as 
have  been  made  of  approximately  pure  human  gastric  juice  a  smaller 
percentage  of  hydrochloric  acid  has  usually  been  obtained  (at  most 
0-35  to  0-4  per  cent.).  But  there  is  some  reason  to  believe  that  if 
the  human  juice  could  be  collected  in  a  faultless  manner,  and 
especially  free  from  any  admixture  with  saHva  or  with  a  pathological 
secretion  of  mucus,  it  would  show  as  high  a  percentage  of  acid  as 
the  dog's  juice. 

In  cases  of  cancer,  whether  the  growth  is  situated  in  the  stomach 
or  not,  the  free  hydrochloric  acid  of  the  gastric  juice  is  usually 
much  reduced,  and  often  absent.  Under  such  conditions  some 
lactic  acid  may  be  present  in  the  stomach,  being  produced  from  the 
carbo-hydrates  by  the  action  of  bacteria  {Bacillus  acidi  ladici), 
which  are  normally  held  in  check  by  the  hydrochloric  acid,  although 
not  rendered  incapable  of  growth  when_  they  have  passed  on  into 
the  intestine.  Even  in  the  strength  of  0-07  to  o-o8  per  cent,  hydro- 
chloric acid  prevents  the  formation  of  lactic  acid  from  dextrose. 
Indeed,  when  all  the  hydrochloric  acid  of  the  gastric  juice  is  com- 
bined with  proteins,  the  protein-acid  compound  still  inhib'ts  the 
growth  of  bacteria  in  the  stomach,  although  not  so  efificieiitly  as  the 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  345 

same  amount  of  free  acid.  That  in  normal  gastric  juice  the  acidity 
is  not  due  to  lactic  acid  can  be  shown  by  shaking  the  juice  with 
ether  which  takes  up  lactic  acid,  and  then  applying  Ufielmann's 
test  to  the  ethereal  extract  (Practical  Exercises,  p.  454). 

More  than  this,  it  is  not  due  to  an  organic,  but  to  an  inorganic 
acid,  for  healthy  gastric  juice  causes  such  an  alteration  in  the 
colour  of  anihne  dyes  like  congo-red  and  methyl  violet  as  would 
be  produced  by  dilute  mineral  acids,  and  not  by  organic  acids,  even 
when  present  in  much  greater  strength.*  Finally,  when  the  bases 
and  acid  radicles  of  the  juice  are  quantitatively  compared,  it  is 
found  that  there  is  more  chlorine  than  is  required  to  combine  with 
the  bases;  the  excess  must  be  present  as  free  hydrochloric  acid. 
In  the  pure  gastric  juice  of  fishes  like  the  dogfish  and  skate,  however, 
the  acid  is  said  not  to  be  hydrochloric  but  an  organic  acid.  The 
quantity  of  gastric  juice  secreted  depends  upon  the  nature  and 
amount  of  the  food.  It  has  been  estimated  at  as  much  as  5  litres 
in  twenty- four  hours,  or  several  times  the  quantity  of  saliva  secreted 
in  the  same  time.  With  sham  feeding  a  dog  may  yield  200-300  c.c. 
in  an  hour. 

The  great  action  of  gastric  juice  is  upon  proteins.  In  this  two 
of  its  constituents  have  a  share,  the  pepsin  and  the  free  acid.  One 
member  of  this  chemical  copartnery  cannot  act  without  the  other ; 
peptic  digestion  requires  the  presence  both  of  pepsin  and  of  acid ; 
and,  indeed,  an  active  artificial  juice  can  be  obtained  by  digesting 
the  gastric  mucous  membrane  with  dilute  (0-2  to  0-4  per  cent.) 
hydrochloric  acid.  A  glycerin  extract  of  a  stomach  which  is  not 
too  fresh  also  possesses  peptic  power,  the  zymogen  or  mother 
substance,  pepsinogen,  having  been  activated  to  pepsin.  Free 
acid  very  readily  effects  this  activation,  but  this  is  far  from  being 
the  only  function  of  the  hydrochloric  acid,  for  active  pepsin  still 
requires  the  addition  of  a  sufficient  quantity  of  acid  to  render  its 
proteolytic  power  available. 

Well-washed  fibrin  obtained  from  blood  is  a  convenient  protein 
for  use  in  experiments  on  digestion;  although,  of  course,  for  many 
purposes  only  isolated  purified  proteins  can  be  employed.  Since  the 
blood  contains  traces  of  pepsin,  the  fibrin  should  be  boiled  to  destroy 
any  which  may  be  present  (see  also  p.  447). 

If  we  place  a  little  fibrin  in  a  beaker,  cover  it  with  gastric  juice 
obtained  from  a  dog  or  with  0*4  per  cent,  hydrochloric  acid,  to  which  a 
small  quantity  of  pepsin  or  of  a  gastric  extract  has  been  added,  and 
put  the  beaker  in  a  water-bath  at  40°  C,  the  fibrin  soon  swells  up  and 
becomes  translucent,  then  begins  to  be  dissolved,  and  in  a  short  tinic 
has  disappeared  (see  Practical  Exercises,  p.  452).     If  we  examine  the 

*  A  dilute  solution  of  congo-rcd  is  turned  violet  by  organic  and  blue  by 
inorganic  acids;  the  gastric  juice  turns  it  blue.  Methyl  violet  is  rendered  blue 
by  an  inorganic  acid  like  hydrochloric  acitl.  and  green  if  more  of  the  acid  be 
added.      It  is  not  altered  by  organic  acids.     Gastric  juice  turns  it  blue. 


346  DIGESTION 

liquid  before  digestion  has  proceeded  very  far,  we  shall  find  chiefly 
so-called  acid-albumin  in  solution;  later  on,  chiefly  albumoscs;  and  of 
these  some  authors  distinguish  the  primary  albumoses  (proto-albumose 
and  hetero-albumose),  the  first  to  appear  in  quantity,  followed  by 
secondary  or  deutero-albumoses  (p.  lo).*  Still  later,  peptones  in  large 
and  always  relatively  increasing  amounts  will  be  present  along  with 
the  alburnoses.  From  this  we  conclude  that  acid-albumin  is  a  stage 
in  the  conversion  of  fibrin  into  albumose,  and  albumose  a  half-way 
house  between  acid-albumin  and  peptone.  It  must  not  be  supposed, 
however,  that  all  the  protein  is  first  changed  into  acid-albumin  before 
any  of  the  acid-albumin  is  changed  into  albumose,  or  that  all  the 
protein  has  already  reached  the  albumose  stage  before  peptone  begins 
to  appear.  On  the  contrary,  a  certain  amount  of  albumoses  and  of 
peptones  are  present  very  early  in  peptic  digestion,  while  the  greater 
part  of  the  original  protein  is  still  unaltered.  Among  the  somewhat 
vaguely  characterized  group  of  bodies  comprised  under  the  term 
peptones,  there  are  no  doubt  decomposition  products  of  the  proteins 
in  which  the  hydrolysis  has  been  carried  to  different  degrees.  Similar, 
but  not  identical,  intermediate  substances  occur  in  the  digestion  of  the 
other  proteins,  including  that  of  bodies  like  gelatin,  which  are  not 
ordinary  proteins,  but  which  pepsin  can  digest.  The  generic  name  of 
proteose  properly  includes  all  bodies  of  the  albumose  type,  the  term 
'  albumose  '  itself  being  sometimes  reserved  for  such  intermediate 
products  of  the  digestion  of  albumin;  while  those  of  fibrin  are  called 
fibrinoses;  of  globulin,  globuloses;  of  casein,  caseoses;  and  so  on.  The 
peptones  produced  from  different  proteins  are  also  not  absolutely 
identical.  If  the  digestion  is  prolonged,  the  peptones  first  formed  are 
in  turn  further  hydrolysed,  so  that  eventually  a  considerable  proportion 
of  the  original  protein  is  converted  into  bodies  which  no  longer  give  the 
biuret  reaction. 

In  the  stomach,  during  the  four  or  five  hours  for  which  gastric 
digestion  ordinarily  lasts,  none  of  the  protein  passes  beyond  the 
stage  of  proteose  and  peptone,  including  those  relatively  simple 
'  abiuret  '  compounds  which  still  consist  of  several '  building- stones,' 
chiefly,  it  would  seem,  the  amino-acids,  phenylalanin,  and  prohn, 
linked  together.  When  precautions  are  taken  to  prevent  the 
passage  of  any  portion  of  the  contents  of  the  duodenum  into  the 
stomach,  no  amino-acids  can  be  detected  in  the  gastric  contents 
during  the  digestion  of  protein.  In  this  connection  it  is  interesting 
to  note  that  none  of  the  polypeptides  hitherto  prepared  (p.  2)  are 
decomposed  by  pepsin.  It  is  not  known  at  what  points  in  the  link- 
age of  the  groups  that  compose  the  complex  protein  molecule  the 
pepsin  ruptures  the  chain,  but  the  points  of  attack  are  different  from 
those  of  trypsin.     The  pancreatic  juice,  as  we  shall  see  later  on,  not 

*  In  the  light  of  modern  investigation  the  results  of  fractional  precipitation 
by  salts  of  the  products  of  proteolysis  have  lost  a  good  deal  of  their  interest, 
and  it  is  seen  that  undue  importance  has  often  been  attached  to  them.  The 
student  should  be  warned  that  such  terms  as  '  albumose  '  and  '  peptone  '  do 
not  indicate  precise  chemical  differences  between  the  products  separated  in 
this  way,  nor  even  invariably  such  differences  in  molecular  weight  as  the 
current  schemata  of  the  digestive  processes  are  apt  to  imply.  Some  so-called 
'  peptones'  may  indeed  have  a  higher  molecular  weight  and  be  more  nearly 
related  to  the  original  protein  than  some  so-called  '  albumoses.' 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  347 

only  effects  a  more  complete  conversion  into  peptones,  but  can  split 
up  the  whole  or  a  very  large  proportion  of  the  peptones  themselves 
into  amino-acids  and  the  other  '  building-stones  '  of  the  original 
protein.  Since  the  subject  of  protein  digestion  must  come  up  again, 
it  will  be  well  to  postpone  any  closer  discussion  of  the  process  till  we 
can  view  it  as  a  whole.  In  the  meantime  it  is  only  necessary  to 
repeat  that  pepsin  alone  cannot  digest  proteins  at  all.  Its  action 
requires  the  presence  of  an  acid;  in  a  neutral  or  alkaline  medium 
peptic  digestion  stops.  The  precise  mode  of  action  of  the  acid  is  by 
no  means  clear. 

Dilute  acid  alone  does  not  dissolve  coagulated  proteins  like  boiled 
fibrin,  or  does  so  only  with  extreme  slowness.  But  it  causes  them  to 
swell  up  by  imbibition  of  water,  and  probably  in  this  way  facilitates 
the  entrance  of  the  ferment.  Uncoagulated  proteins  are  readily 
changed  by  acid  into  acid-albumin ;  and  by  the  prolonged  action  of 
acids,  especially  at  a  high  temperature,  further  changes  of  much  the 
same  nature  as  those  produced  in  peptic  digestion  may  be  caused  in 
all  proteins.  But  under  the  ordinary  conditions  of  natural  gastric 
digestion,  it  may  be  said  that  the  acid  alone  does  little  until  it  is 
aided  by  the  ferment,  just  as  the  ferment  alone  does  nothing  \\'ithout 
the  aid  of  the  acid.  The  acid  enters  into  a  temporary  combination 
with  the  protein,  the  more  highly  hydrolysed  proteins,  such  as 
peptones,  combining  with  a  greater  proportion  of  acid  than  such 
proteins  as  fibrin  or  albumin.  These  compounds  so  easily  undergo 
hydrolytic  dissociation  that,  in  spite  of  its  union  with  the  proteins, 
the  hydrochloric  acid  is  able  to  act  along  \\ith  the  pepsin,  so  that 
peptic  digestion  goes  on  even  when  enough  protein  is  present  to 
combine  with  all  the  acid.  There  is  some  evidence  that  in  the 
gastric  juice  the  pepsin  exists  in  the  form  of  an  unstable  compound 
with  hydrochloric  acid,  and  it  is  probably  this  pepsin-hydrochloric 
acid  compound  which  is  the  actual  catalytic  agent  in  peptic  digestion. 
Although  hydrochloric  acid  acts  most  powerfully,  other  acids,  such 
as  nitric,  phosphoric,  sulphuric,  or  lactic  (arranged  in  the  order  of 
their  efficacy),  can  replace  it. 

The  Milk-Curdling  Action  of  Gastric  Juice. — The  milk-curdhng 
ferment,  rennin,  or  chymosin,  is  contained  in  large  amount  in  an 
extract  of  the  fourth  stomach  of  the  calf,  which,  as  rennet,  has  long 
been  used  in  the  manufacture  of  cheese.  It  exists  in  the  healthy 
gastric  juice  of  man,  but  disappears  in  cancer  of  the  stomach  and  in 
chronic  gastric  catarrh.  It  has  been  stated  by  a  number  of  observers 
that  the  properties  of  rennin  are  never  found  in  gastric  juice  or  any 
preparation  obtained  from  it  or  from  the  gastric  mucous  membrane 
unless  pepsin  is  present.  This  has  suggested  that  there  is  no  separate 
milk-curdling  ferment,  but  that  the  clotting  or  precipitation  of 
caseinogcn  is  merely  an  associated  action  of  the  pepsin.  Ferments 
of  the  most  varied  origin  will  curdle  milk.     Pawlow  has  maintained 


348  DIGESTION 

that  the  milk-curdling  property  not  only  of  the  gastric  juice,  but  also 
of  the  pancreatic  juice  and  of  the  secretion  of  Brunner's  glands,  is 
associated  with  the  proteolytic  ferment. 

He  asserts  that  when  the  comparison  is  instituted  under  proper 
conditions  there  is  an  exact  parallelism  between  the  proteolytic  and 
the  milk-curdUng  power  of  these  secretions,  no  matter  what  the 
circumstances  may  be  in  which  they  are  collected,  or  the  influences 
to  which  they  are  exposed  after  collection.  He  has  found  it  im- 
possible to  separate  from  any  one  of  them  a  fraction  which  has 
milk-curdling  power  without  proteolytic  power.  On  the  other  hand, 
the  majority  of  investigators  maintain  the  separate  identity  of 
rennin.  Hammarsten  especially  states  that  he  can  destroy  the 
peptic  activity  without  destroying  the  milk-curdhng  power  of  gastric 
extracts,  and  vice  versa.  According  to  Burge,  when  a  solution  dis- 
playing both  peptic  and  milk-curdling  power  is  electrolyzed,  the 
pepsin  action  is  abolished  at  a  certain  stage,  while  the  rennet  action 
is  unaffected.  It  would  seem,  then,  that  the  balance  of  evidence 
is  in  favour  of  the  separate  identity  of  the  rennet  enzyme. 

However  this  may  be,  the  curdhng  of  milk  by  the  gastric  ferment 
includes  two  processes:  (i)  An  action  on  caseinogen  in  the  course  of 
which  it  acquires  new  properties,  becoming  changed  into  casein. 
This  substance  is  not  capable  of  being  converted  into  casein, 
and  remains  in  solution  in  the  whey.  (2)  The  altered  casein- 
ogen or  casein  combines  with  soluble  calcium  salts  and  in  the 
presence  of  these  is  precipitated  as  the  curd.  The  change  which 
occurs  in  the  caseinogen  has  been  the  subject  of  much  discussion, 
which  has  not  yet  led  to  a  definite  conclusion.  According  to  some 
observers,  the  change  consists  in  a  decomposition  of  caseinogen,  in 
the  course  of  which  a  new  substance,  whey-protein,  not  previously 
present  in  the  milk,  is  split  off.  This  substance  is  not  capable  of 
being  precipitated  by  lime  salts,  and  remains  in  solution  in  the  whey. 
According  to  others,  the  molecule  of  caseinogen  is  simply  changed 
into  two  molecules  of  casein  (van  Slyke).  Dilute  acid  will  of  itself 
precipitate  caseinogen,  and  the  presence  of  acid,  and  particularly 
hydrochloric  acid,  in  the  gastric  juice  helps  its  milk-curdling  action. 
But  that  a  ferment  is  really  concerned  is  indicated  by  the  fact  that 
the  juice,  after  being  made  neutral  or  alkaline,  still  curdles  milk,  and 
that  this  power  is  destroyed  by  boiling.  The  optimum  temperature 
is  the  same  as  that  of  the  other  ferments  of  the  digestive  tract,  about 
40°  C.  (p.  331).  The  persistence  of  the  milk-curdhng  activity  in  the 
presence  of  OH  ions,  while  for  peptic  activity  free  H  ions  are  neces- 
sary, is  a  further  and,  indeed,  a  strong  argument  in  favour  of  the 
separate  existence  of  the  rennet  ferment. 

As  to  the  exact  function  of  the  milk-curdling  ferment  of  the 
gastric  juice  in  digestion,  we  have  no  precise  knowledge.  It  seems 
superfluous  if  we  suppose  that  the  free  acid  is  able  of  itself  to  do  all 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  349 

that  the  ferment  does  along  with  it.  But  there  is  evidence  that  the 
curd  produced  by  the  ferment  is  more  profoundly  changed  than  the 
precipitate  caused  by  dilute  acids;  for  the  latter  may  be  redissolved, 
and  then  again  curdled  by  rennin  in  the  presence  of  calcium  salts, 
while  this  cannot  be  done  with  the  former.  We  may  suppose,  then, 
that  the  ferment  is  capable  of  effecting  changes  more  favourable  to 
the  subsequent  action  of  the  pepsin  upon  the  casein  than  those 
which  the  acid  alone  would  effect.  Or  it  may  be  that  the  ferment 
acts  in  the  early  stages  of  digestion  before  much  acid  has  been 
secreted.  The  curdling  of  milk  probably  plays  a  part  in  ensuring 
the  retention  of  this  food,  the  proper  digestion  of  which  is  all-impor- 
tant for  the  suckling,  for  a  sufficient  length  of  time  in  the  stomach. 
Otherwise,  hke  water  and  watery  hquids  in  general,  it  would  be 
rapidly  passed  into  the  duodenum.  Even  if  this  were  not  the  case, 
there  is  another  reason  for  early  curdling.  Milk  is  a  very  dilute 
food,  and  the  immense  proportion  of  water  in  it  might  weaken  the 
gastric  juice  too  much  for  rapid  digestion  of  the  proteins.  The 
separation  of  the  whey  and  its  prompt  escape  through  the  pylorus 
would  obviate  this.  But  caution  should  be  exercised  in  giving  a 
physiological  value  to  all  the  details  of  the  milk-curdling  action  of 
the  gastric  juice.  Milk-curdling  ferments,  or,  at  any  rate,  ferments 
wath  a  milk-curdling  influence,  have  an  extremely  wide  distribution, 
both  in  secretions  which  in  normal  circumstances  can  never  come 
into  contact  with  milk,  and  in  the  tissues  of  animals  and  plants. 
Many  bacteria  produce  them.  And  it  appears  that  in  the  suckling, 
where  it  might  be  expected,  if  anywhere,  to  have  a  definite  and 
important  office,  the  rennet  action  of  the  gastric  juice  is  distinctly 
less  than  in  the  adult.  It  is  worthy  of  note  that  the  curd  formed  by 
rennet  from  human  milk  is  more  finely  divided  than  that  formed 
from  cow's  milk,  and  therefore  is  more  easUy  digested.  The  addition 
of  hme-water  or  barley-water  to  cow's  milk  keeps  the  curd  from 
adhering  in  large  masses,  and  thus  aids  its  digestion — a  fact  which 
is  sometimes  usefully  applied  in  the  artificial  feeding  of  infants. 

Gastric  Lipase. — On  fats  gastric  juice  has  usually  been  supposed 
to  have  no  action,  although  everybody  admits  that  it  will  dissolve 
the  protein  constituents  of  fat-cells  and  the  protein  substances  which 
keep  the  fat-globules  of  milk  apart  from  each  other.  It  has,  how- 
ever, been  recently  shown  that  both  in  the  stomach  and  in  vitro 
(with  glycerin  extracts  of  the  gastric  mucous  membrane)  a  consider- 
able amount  of  well -emulsified  fat  may  be  split  up,  and  that  this  is 
due  to  a  ferment  which  is  different  in  several  respects  from  the 
lipase  of  pancreatic  juice.  Gastric  juice  splits  up  fat,  both  in 
neutral  and  in  weakly  acid  solutions.  The  sUghtest  excess  of  alkali 
checks  the  action.  The  glycerin  extract  is  much  more  resistant  to 
alkali,  while  very  sensitive  to  hydrochloric  acid.  This  indicates 
that  the  fat-splitting  ferment  exists  in  the  mucous  membrane  in  a 


350  DIGESTION 

different  form  from  that  in  which  it  exists  in  the  juice — namely,  as 
a  zymogen  or  mother-substance.  But  while  the  zymogen  of  the 
pancreatic  lipase  is  activated  by  bile,  this  is  not  the  case  with  the 
mother-substance  of  the  gastric  lipase.  It  appears  that  in  the 
suckling  the  lipase  of  the  gastric  juice  plays  a  more  important  part 
than  in  later  life.  This  is  obviously  in  accordance  with  the  fact  that 
the  specific  food  of  the  suckling — milk — contains  as  an  essential  con- 
stituent a  large  proportion  of  emulsified  fat.  The  conditions  for 
the  emulsification  of  fat  do  not  exist  in  the  gastric  juice,  and  this  is 
the  reason  why  the  gastric  lipase  has  so  slight  an  effect  upon  un- 
emulsified  fat,  which  presents  a  surface  of  contact  proportionally  so 
small.  In  any  case  the  amount  of  fat  hydrolysed  in  the  stomach 
under  ordinary  conditions  is  small  in  comparison  with  the  amount 
split  in  the  intestine,  although  it  has  been  shown  that  with  a  diet 
rich  in  fat  some  of  the  intestinal  contents,  including  pancreatic 
lipase,  may  pass  back  into  the  stomach. 

As  regards  the  carbo-hydrates,  the  swallowed  saliva  will  continue 
to  act  on  starch  in  the  stomach,  so  long  as  the  acidity  is  not  too  great ; 
while  the  hydrochloric  acid  of  the  gastric  juice  is  able  to  invert  cane- 
sugar,  changing  it  into  a  mixture  of  dextrose  and  levulose,*  and 
also,  doubtless,  to  hydrolyse  to  dextrose  a  portion  of  the  maltose 
formed  by  the  saliva.  Altogether,  there  is  no  doubt  that  the  pro- 
portion of  the  carbo-hydrates  of  the  food  digested  in  the  stomach  is 
far  from  insignificant. 

The  Antiseptic  Function  of  the  Gastric  Juice. — The  stomach,  with 
its  acid  contents,  forms  during  the  greater  part  of  gastric  digestion 
a  valve  or  trap  to  cut  off  the  upper  end  of  the  intestine  from  the 
bacteria-infested  regions  of  the  mouth  and  pharynx,  and  to  destroy 
or  inhibit  the  micro-organisms  swallowed  with  the  food  and  saliva. 
The  occasional  presence  in  vomited  matter  of  sarcinae  or  regularly 
arranged  groups  of  micrococci,  generally  four  to  a  group,  shows  that 
under  abnormal  conditions  the  gastric  contents  are  not  perfectly 
aseptic;  and  even  from  a  normal  stomach  active  micro-organisms 
of  various  kinds  can  be  obtained.  But  upon  the  whole  there  is  no 
doubt  that  the  acidity  of  the  gastric  juice  is  an  important  check  on 
bacterial  activity  during  the  first  part  of  digestion,  and  in  the  upper 
portion  of  the  ahmentary  canal.  Koch  has  shown  that  the  acidity 
of  the  gastric  juice  of  a  guinea-pig  is  sufficient  to  kill  the  comma 
bacillus  of  cholera.     Normal  guinea-pigs  fed  with   oholcra  bacilli 

♦  These  are  both  reducing  sugars,  but,  as  their  names  indicate,  they  rotate 
the  plane  of  polarization  in  opposite  directions.  The  specific  rotatory  power 
of  levulose  is  greater  tlian  that  of  dextrose,  so  that  when  cane-sugar  is  com- 
pletely inverted,  although  equal  quantities  of  dextrose  and  levulose  are  pro- 
duced, the  plane  of  polarization  is  rotated  to  the  left.  Cane-sugar  itself  rotates 
it  to  the  right.  The  term  '  inversion  '  has  been  extended  to  include  the 
similar  hydrolysis  of  other  sugars  of  the  disaccharide  group — e.g.,  maltose  to 
dextrose,  and  lactose  to  a  mixture  of  dextrose  and  galactose,  even  although 
the  products  are  not  levo-rotatory. 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  351 

were  unaffected.  But  if  the  gastric  juice  was  neutralized  by  an 
alkali  before  the  administration  of  the  bacilli  the  guinea-pigs  died. 
Charrin  found,  too,  that  digestion  with  pepsin  and  hydrochloric  acid 
causes  an  appreciable  destruction  or  attenuation  of  diphtheria  toxin. 
Bacteria,  hke  the  lactic  acid  bacillus,  which  form  acid  products,  may 
be  less  profoundly  affected  by  the  acid  gastric  juice  than  the  putre- 
factive bacteria,  which,  on  the  whole,  form  alkalies,  and  are  there- 
fore accustomed  to  an  alkaline  medium.  Yet  we  have  seen  that  the 
growth  of  even  the  lactic  acid  bacillus  is  very  strictly  controlled  when 
the  gastric  juice  contains  the  normal  amount  of  hydrochloric  acid. 
It  has  been  supposed  by  some  that  this  bactericidal  action  is  the 
chief  function  of  the  stomach,  and  the  question  has  been  asked  why 
we  should  attribute  any  digestive  importance  to  the  secretion  of  that 
viscus,  since  the  pancreatic  juice  can  do  all  that  the  gastric  juice 
does,  and  some  things  which  it  cannot  do.  Further,  it  has  been 
shown  that  a  dog  may  live  five  years  after  complete  excision  of  the 
stomach,  comport  himself  in  all  respects  hke  a  normal  dog,  and  when 
killed  for  necropsy  show  every  organ  in  perfect  health  (Czerny).  In 
man,  too,  the  stomach  has  been  excised  with  a  successful  result. 
But  if  this  is  to  be  admitted  as  evidence  against  the  digestive  function 
of  the  stomach,  it  is  just  as  good  evidence  against  the  bactericidal 
function,  particularly  as  it  has  in  addition  been  shown  that  even 
putrid  flesh  has  no  harmful  effect  on  a  dog  after  excision  of  the 
stomach,  any  more  than  on  a  normal  dog.  And,  indeed,  the  reason- 
ing is  fallacious  which  assumes  that  what  may  happen  under  ab- 
normal conditions  must  happen  when  the  conditions  are  normal. 
For  nothing  is  impressed  more  often  on  the  physiological  observer 
than  the  extraordinary  power  of  adaptation,  of  making  the  best  of 
everything,  which  the  animal  organism  possesses.  Doubtless  a  dog 
without  a  stomach  will  use  to  the  best  advantage  the  digestive  fluids 
that  remain  to  him ;  and  the  pancreatic  juice,  with  the  aid  of  the  bile 
and  the  succus  entericus,  may  be  adequate  to  the  complete  task  of 
digestion.  So,  too,  a  man  from  whom  the  surgeon  has  removed  a 
kidney,  or  a  testicle,  or  a  lobe  of  the  th}Toid  gland,  may  be  in  no 
respect  worse  off  than  the  man  who  possesses  a  pair  of  these  organs. 
But  what  do  we  deduce  from  this  ?  Not,  surely,  that  the  excised 
thyroid,  or  testicle,  or  kidney  was  useless,  or  the  gastric  juice  in- 
active, but  that  the  organism  has  been  able  to  compensate  itself  for 
their  loss.  Further,  it  would  seem  that  the  fate  of  the  protein  or  of 
part  of  the  protein  digested  and  absorbed  by  the  stomach  is  different 
from  that  digested  and  absorbed  by  the  intestine.  For  after  the 
operation  of  gastro-enterostomy  (the  establishment  of  an  artificial 
opening  between  the  stomach  and  the  small  intestine  through  which 
the  food  passes  rapidly  without  having  to  submit  to  the  challenge 
of  the  pyloric  sphincter),  the  ingested  nitrogen  is  more  quickly 
eliminated  than  when  the  protein  is  first  subjected  to  full  gastric 


352  DIGESTION 

digestion.  So  that  when  the  quantity  of  protein  in  the  food  is 
increased  above  that  necessary  for  nitrogen  equihbrium  (p.  594),  none 
of  the  excess  is  assimilated  and  stored  up,  as  is  the  case  in  a  normal 
animal  (Levin,  etc.). 

Pancreatic  Juice- — Pancreatic  juice,  bile,  and  intestinal  juice  are 
all  mingled  together  in  the  small  intestine,  and  act  upon  the  food, 
not  in  succession,  but  simultaneously.  But  by  artificial  fistulae  in 
animals  they  can  be  obtained  separately;  and  occasionally  some  of 
them  can  be  procured  through  accidental  fistulae  in  man.  It  is  said 
that  under  certain  conditions,  especially  when  fat  or  oil  is  introduced 
into  the  stomach,  the  pylorus  may  remain  open  long  enough  to 
permit  the  passage  of  pancreatic  juice  or  bile  from  the  duodenum  into 
the  stomach,  and  this  has  been  recommended  as  a  practical  method 
of  obtaining  these  secretions  in  man. 

Human  pancreatic  juice,  as  obtained  from  a  fistula,  is  a  clear,  only 
shghtly  viscid  hquid  of  distinctly  alkahne  reaction  to  litmus.  Its 
specific  gravity  is  about  1007  to  loio.  The  total  solids  constitute 
about  1-5  or  2  per  cent.,  of  which  a  little  less  than  i  per  cent,  is  made 
up  of  inorganic  salts,  chiefly  sodium  carbonate,  with  small  quantities 
of  chlorides.  The  balance  of  the  solids  consists  mainly  of  proteins. 
The  alkahne  reaction  is  due  to  the  sodium  carbonate,  and  it  is 
worthy  of  remark,  as  showing  the  important  part  taken  by  this 
secretion  in  the  neutralization  of  the  chyme,  that  when  titrated 
against  standard  acid  the  alkalinity  of  the  pancreatic  juice  is  not 
much  less  than  the  acidity  of  the  gastric  juice  when  titrated  against 
standard  alkali.  The  quantity  of  pancreatic  juice  secreted  during 
the  twenty- four  hours  in  an  average  man  has  been  estimated  at 
500  to  800  c.c.  from  observations  on  cases  of  fistula.  Probably 
under  perfectly  normal  conditions  it  is  greater.  A  so-called  arti- 
ficial pancreatic  juice  can  be  made  by  extracting  the  pancreas  with 
water  or  glycerin.  Since  better  methods  of  obtaining  the  natural 
juice  have  been  developed,  these  extracts  have  lost  some  of  their 
importance. 

Fresh  pancreatic  juice  contains  four  ferments:  (i)  The  zymogen  or 
mother-substance,  trypsinogen,  of  a  proteolytic  or  protein-digesting 
ferment,  trypsin  ;  (2)  an  amylolytic  ferment,  or  amylase  ;  (3)  a  fat- 
splitting  or  lipolytic  ferment,  steapsin  ;  (4)  a  milk-curdling  ferment. 
The  question  whether  the  last  is  a  different  body  from  the 
proteolytic  ferment  has  been  discussed  just  as  in  the  case  of  the 
gastric  rennin  (see  p.  347).  In  any  case,  it  cannot  be  considered  as 
taking  any  practical  share  in  digestion,  since  it  can  hardly  ever 
happen  that  milk  passes  through  the  stomach  without  being  curdled. 

Trypsinogen  has  no  action  upon  proteins,  but  in  normal  digestion 
it  is  changed  into  active  trypsin  by  the  enterokinase  of  the  intestinal 
juice  (p.  366).  Pancreatic  juice  collected  without  contact  with 
intestinal  contents  or  with  the  mucous  membrane  of  the  intestine 


THE  CHEMISTRY  Ob   THE  DIGESTIVE  JUICES  353 

does  not  digest  proteins.  The  same  is  true  of  extracts  of  perfectly 
fresh  pancreas,  but  if  the  pancreas  is  allowed  to  stand  for  a  time,  the 
extracts  contain  active  trypsin,  perhaps  because  some  decomposition 
product  has  activated  the  trypsinogen.  Some  writers,  however, 
state  that  when  contamination  of  the  gland  with  intestinal  contents 
or  contact  with  the  mucosa  has  been  avoided  in  its  removal  from 
the  body,  such  extracts  will  remain  inactive  for  months,  although 
the  trypsinogen  can  at  once  be  activated  to  trypsin  by  the  addition 
of  enterokinase. 

Trypsin,  to  a  certain  extent,  corresponds  with  pepsin  in  its  action 
on  proteins.  But  it  acts  energetically  in  an  alkaline  as  well  as  in  a 
not  too  acid  medium  (a  very  slight  amount  of  digestion  may  go  on  in 
distilled  water) ;  and  its  action,  unlike  that  of  pepsin — at  least  in 
digestions  of  moderate  duration — does  not  stop  at  the  peptone  stage, 
but  goes  on  rapidly  to  the  production  of  the  amino-acids,  the  basic 
substances  arginin,  lysin,  and  histidin,  known  as  the  hexone  bases, 
and  most  of  the  other  decomposition  products  obtained  by  boiling 
proteins  with  dilute  acids.  The  most  important  of  these  products, 
so  far  as  they  have  been  isolated  and  identified,  are  enumerated  in 
the  table  on  p.  354  (see  also  pp.  1-3). 

As  to  the  chemical  nomenclature  of  these  bodies,  the  student  should 
refer  to  his  textbook  of  organic  chemistry.  It  need  only  l)c  remarked 
here,  by  way  of  ilhistration,  that  when,  e.g.,  leucin  is  designated  as 
a-amino-isobutylacctic  acid,  this  indicates  that  it  can  be  derived  from 
the  fatty  acid  isobutylacetic  acid  by  the  substitution  of  an  amino  group, 
NHo,  for  a  hydrogen  atom  in  the  a-carbon  group  (see  p.  547)  of  the 
fatty  acid — i.e.,  the  group  next  the  carboxyl  (COOH)  group.     Thus, 

^g^^CH.CHa-CHa.COOH  ,  J^fJsXcH.CHo.CH.COOH. 
CH3/  \     2  'CH3/  I 

Isobutylacelic  acid.  Leucin.      JNrl2 

When  norleucin,  an  amino-acid  found  especially  in  the  proteins  of 
nervous  tissue,  is  termed  a-amino-caproic  acid,  it  is  indicated  that  NH2 
replaces  one  H  in  the  nCHo  group  of  caproic  acid  (CH3.CH2.CH2.CH2. 
CH2COOH).  The  long  chemical  name  of  isolcucin  (a  compound  also 
derived  from  the  proteins  of  nervous  tissue  and  from  some  plant  proteins) 
indicates  that  in  propionic  acid, 

CI:f3.CH.^.COOH, 

^       a 
NH2  is  introduced  into  the  a  group,  yielding 

CH3.CH.COOH, 

/3        I 
NHo 

or  amino-propionic  acid  (alanin) ;  while  in  the  /3  group  one  H  is  replaced 
by  a  methyl  (CH3)  group,  and  another  H  by  an  ethyl  (C2H5)  group, 
yielding  finally  isonuclein: 

^^3\cH.CH.COOH. 

NH2 

23 


354 


DIGESTION 


CHIEF  DECOMPOSITION  PRODUCTS  OF  PROTEINS. 


MONOAMINO-ACIDS    AND    THEIR    COMPOUNDS. 

/Glycin  or  glycocoU  (aminoacetic  acid),  CN2(HN2)COOH. 
Alanin  (aminopropionic  acid),  CH3CH(NH2)COOH. 
Serin  or  oxvalanin  (oxyaminopropionic  acid), 

CH20H.CH(NH2).COOIl. 


Valin  or  aminovalerianic  acid,  ^^j^ 


CHg^ 

Leucin  (a-aminoisobutylacetic  acid)  q^^ 


CHCH(NH2)COOH. 
CHj 

3/ 
Norleucin  (a-amino-caproic  acid), 

CH3.CH2.CH2.CH2.CH(NH2)  .COOH . 
Isoleucin  (o-amino-j3-methyl-/3-ethyl-propionic  acid), 

(?^3  \cH  .CH  (NHa)  .COOH . 

Cystein  (n  -  amino-/3  -  thiopropionic   acid),  CHg  (SH).CH(NH2)COOH, 
which    is    unstable,    two    molecules    of    it    easily    yielding    cystin 
di-(a-amino-/3-thiopropionic  acid) , 
\  COOH.CH(NH2).CH2.S.S.CH2.CH(NH2).COOH. 


)CHCH2CH{NH2)COOH. 


in  jn 


TAspartic  or  aminosuccinic  acid,  CH(NH2).COOH. 

]  CHgCOOH. 

I  Glutamic  or  glutaminic  acid,  CH2<^gJJ ^^'^^^^jf  °^^ 


(U    O    O 


g'^.>  TTyrosin  (para-oxyphenylaminopropionic  acid), 
N  c  ri  ^  CfiH.Oi: 


e  ^ 


4OH  .Cl  IgCH  (NH2)  .COOH . 


<u  g  -  ( Phenylalanin  (phenylaminopropionic  acid),  C6ll5CH2CH(NH2)COOH. 


■Ho  9 

^  "O  ■- 

"O-S  "S 
'-'  --^   > 

1-.  t3  .;;; 


'  Prolin  (pyrrolidin  carboxylic  acid). 
Oxyprolin  (oxypyrrolulin  carbo.xylic  acid). 
Tryptophane  (a-aniino-/3-indol-propionic  acid), 

/NH— CH 
HC 


^N  —  C— CH2.CH(NH2).COOH. 


Histidin  (/J-imidazol-a-aminopropionic  acid),  C6H9N3O2 


DIAMINO-ACIDS    AND    THEIR    COMPOUNDS. 

o.     I'Lysin  (a-amino-€-amino-caproic  acid,  CH2NH2(CH2)3CH(NH2)COOH. 
«  o  ^  I  Arginin  (guanidinaminovalerianic  acid). 


JiXi 


HN=C< 


\NHCH2(CH2)2CH(NH2)COOH. 


Ammonia  (representing  the  so-called  '  amide-nitrogen,'  and  liberated 
from  the  products  of  acid  hydrolysis  of  proteins  by  heating  the 
mixture  after  addition  of  alkali).  It  has  not  been  shown  that 
ammonia  is  itself  one  of  the  '  Bansteine  '  of  the  proteins. 


TIIK  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  355 

In  the  artilicici,!  compounds  of  two  or  more  amino-acids  which  have 
been  synthesized  by  Fischer  and  named  by  him  polypeptides  (p.  2), 
the  carboxyl  group  of  one  amino-acid  is  Hnkcd  with  the  amino  group 
of  another.  For  example,  a  molecule  of  alanin  and  a  molecule  of  glycin 
form,  with  loss  of  a  molecule  of  water,  a  molecule  of  alanyl-glycin, 
according  to  the  equation 


NH2.CH2.CO  OH +  HiNH.CH.CH3— H2O-NH2.CH2.CO.NH.CH.CH,. 

- "'  I  I 

COOH  COOH 

Glycin.  Alanin.  Glycyl-alanin. 

Two  or  more  molecules  of  the  same  amino-acid  can  be  linked  in  the 
same  way;  e.g.,  two  molecules  of  glycin  yield  a  molecule  of  glycyl-glycin, 
and  so  on.  It  has  been  proved  that  polypeptides  identical  with  some  of 
these  synthetic  bodies  are  present  in  the  peptone  mixtures  derived  from 
the  native  proteins,  so  that  it  must  be  assumed  that  one  of  the  ways 
at  least  in  which  amino-acids  are  linked  in  the  protein  molecule  is  that 
described. 

It  has  been  suggested  that  the  early  appearance  of  some  of  these 
amino-acids  in  pancreatic  digestion  is  not  really  due  to  trypsin,  but 
to  other  ferments,  peptases,  which  act  upon  the  peptones  formed  by 
the  trypsin.  There  is,  however,  no  clear  evidence  of  the  existence 
of  a  separate  peptone-splitting  enzyme  in  pancreatic  juice,  Hke  the 
erepsin  of  intestinal  juice,  and  it  is  therefore  most  natural  to  suppose 
that  under  the  influence  of  trypsin  the  protein  molecule  breaks  at 
different  points  from  those  at  which  it  ruptures  under  the  influence 
of  pepsin. 

After  the  most  prolonged  artificial  digestion  with  trypsin,  a 
residue  of  the  protein  remains  unconverted  into  these  relatively 
simple  substances.  But  even  this  small  portion  of  the  original 
protein  has  undergone  a  great  change,  for  it  no  longer  gives  the 
biuret  reaction.  It  can  be  spht  into  amino-acids,  etc.,  by  heating 
with  acid,  and  also  by  the  action  of  the  erepsin  of  the  intestinal  juice, 
and  then  yields  mainly  prolin  and  phenylalanin,  substances  which 
are  generally  not  to  be  detected  among  the  decomposition  products 
of  protein  after  digestion  with  pancreatic  juice.  This  illustratis's  the 
important  fact  that  some  of  the  '  building  stones  '  of  the  protein 
molecule  can  be  separated  from  it  with  far  greater  ease  than  others. 
Tyrosin,  tryptophane,  and  cystin  appear  very  early  in  the  digestive 
fluid,  and  tyrosin,  as  shown  in  the  following  example  from  Abder- 
halden,  may  be  completely  liberated  at  a  time  when  glutaminic  acid 
is  scarcely  more  than  beginning  to  appear. 

The  plant  protein  edestin,  obtained  from  cottonseed,  was  digested 
with  pancreatic  juice  or  an  extract  containing  tr^^psin.  The  quan- 
tities of  tyrosin  and  glutaminic  acid  liberated  at  different  periods 
of  the  experiment  are  expressed  as  percentages  of  the  total  amounts 
of  these  substances  contained  in  the  edestin. 


356 


DIGESTION 


Duration  of  Digestion  : 

I  Day. 

2  Days. 

3  Days. 

7  Days. 

16  Days. 

Tyrosin 
Glutaminic  acid 

78-4 

4'3 

976 

7'4 

976 
109 

100 
311 

100 
6o"2 

\\'hen  trypsin  acts  upon  protein  already  digested  by  pepsin,  this 
partially  hydrolysed  residue  is  smaller  than  when  the  trypsin  acts 
alone,  no  matter  for  how  long  a  time.  Also  the  decomposition  of 
a  given  quantity  of  protein  by  trypsin  is  accomplished  in  a  notably 
shorter  time  if  it  has  been  previously  subjected  to  the  action  of 
pepsin.  This  illustrates  the  co-operative  relation  of  these  two 
ferments — a  relation  still  more  clearly  implied  in  the  fact  that, 
although  trypsin  readily  forms  albumoses  and  peptones  from  native 
protein  when  such  is  offered  to  it,  yet  in  natural  digestion  the  great 
albumose-  and  peptone-forming  ferment  is  pepsin.  In  the  lumen  of 
the  intestine  the  trypsin  is  confronted  mainly  with  protein  already 
hydrolysed  to  the  albumose  and  peptone  stage  in  the  stomach.  In 
other  words,  instead  of  the  very  large  molecules  of  the  original 
protein  food  with  a  weight  of  perhaps  5,000  to  7,000,  the  trypsin 
begins  its  action  on  a  much  larger  number  of  much  smaller  molecules 
of  only  one-twentieth  the  initial  weight  or  less.  The  statement  is 
sometimes  made  that  trypsin  is  a  stronger  proteolytic  ferment  than 
pepsin.  This  may  be  true  in  the  sense  that  trypsin  carries  the  de- 
composition down  to  bodies  of  smaller  molecular  weight  than  pepsin. 
But  within  the  range  of  its  hydrolytic  action  pepsin  decomposes 
certain  proteins  and  alhed  bodies  more  readily  than  trypsin — e.g., 
the  serum  proteins,  and  especially  elastin  and  the  constituents  of 
connective  tissue. 

In  all  that  we  have  hitherto  said  regarding  tryptic  digestion  we 
have  supposed  that  putrefaction  has  been  entirely  prevented — e.g., 
by  the  addition  of  toluol.  If  no  antiseptic  is  added  to  a  tryptic 
digest,  it  rapidly  becomes  filled  with  micro-organisms,  and  emits  a 
very  disagreeable  fcccal  odour;  and  now  various  bodies  which  are  not 
found  in  the  absence  of  putrefaction  make  their  appearance,  such  as 
indol,  skatol,  and  other  substances,  to  which  the  faecal  odour  is  due. 
They  are  not  true  products  of  tryptic  digestion,  but  arc  formed  by 
the  putrefactive  micro-organisms,  which  can  themselves  split  off 
from  proteins  numerous  decomposition  products,  including  tyrosin, 
and  change  tyrosin  into  indol. 

Amylase  or  pancreatic  amylase,  the  diastatic  or  sugar-forming 
ferment  of  pancreatic  juice,  changes  starch  into  dextrin  and  maltose, 
just  as  the  ptyalin  of  saliva  does.  The  two  ferments  are  possibly 
identical,  but  under  the  conditions  of  action  of  the  pancreatic  juice 
its  diastatic  power  is  greater  than  that  of  sahva,  and  it  readily  acts 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  357 

on  raw  starch  as  well  as  boiled.  Pancreatic  amylase  is  mainly, 
perhaps  entirely,  present  in  the  juice  in  the  form  of  active  ferment. 
If  a  zymogen  stage  exists,  the  mother-substance  is  less  stable  or  less 
easily  extracted  from  the  gland  than  is  trypsinogen.  In  this  respect 
amylase  also  resembles  ptyalin.  A  small  amount  of  maltase  is 
contained  in  pancreatic  juice,  and  further  hydrolyses  to  dextrose  a 
portion  of  the  maltose  formed  by  the  amylase. 

Steapsin  or  pancreatic  lipase  splits  up  neutral  fats  into  glycerin  and 
the  corresponding  fatty  acids.  The  latter  unite  with  the  alkaHes  of 
the  pancreatic  juice  and  the  bile  to  form  soaps.  In  this  important 
process  bile  acts  as  the  helpmate  of  pancreatic  juice;  together  they 
effect  much  more  than  either  or  both  can  accomphsh  by  separate 
action.  Many  tissues  contain  fat-splitting  ferments  or  lipases,  some 
of  which  are  perhaps  identical  with  the  pancreatic  hpase.  The  lipase 
exists  as  active  ferment  in  the  pancreatic  juice,  but  there  is  reason 
to  believe  that  a  portion  of  it  may  be  present  as  a  zymogen  in  the 
gland,  and  probably  in  the  secretion  as  well.  It  is  changed  into 
active  ferment  by  the  bile  salts.  Active  lipase  can  also  be  extracted 
from  the  pancreas  by  glycerin  or  water.  It  is  to  be  noted  that  it  is 
only  the  proteolytic  enzyme  which  is  totally  inactive  till  it  reaches 
the  intestine.     The  significance  of  this  will  be  discussed  later  on. 

Bile. — Bile  is  a  liquid  the  colour  of  which  varies  in  different  groups 
of  animals,  and  even  in  the  same  species  is  not  constant,  depending 
on  the  length  of  time  the  fluid  has  remained  in  the  gall-bladder  and 
other  circumstances.  When  it  is  recognized  that  the  colour  is  due 
to  a  series  of  pigments,  which  are  by  no  means  stable,  and  of  which 
one  can  be  caused  to  pass  into  another  by  oxidation  or  reduction, 
this  want  of  uniformity  will  be  easily  intelligible.  The  fresh  bile  of 
carnivora  is  golden-red.  The  bile  of  herbivorous  animals  is  in 
general  of  a  green  tint,  but,  when  it  has  been  retained  long  in  the 
gall-bladder,  may  incline  to  reddish-brown.  Fresh  human  bile,  as 
it  flows  from  a  fistula  just  established,  is  of  a  reddish-brown,  golden- 
yellow  or  yellow  colour.  Beaumont  speaks  of  the  yellowish  bile 
which  he  could  press  into  the  stomach  of  St.  Martin  by  manipulating 
the  abdomen.  In  a  case  observed  by  the  writer,  it  was  seen  that 
when  the  bile  flowing  from  a  fistula  was  allowed  to  spread  out  in  a 
dressing,  it  became  greenish,  because  of  oxidation  of  a  part  of  the 
bilirul)in  to  biliverdin,  although  as  it  actually  escaped  from  the  fistula 
it  was  yellow.  The  bile  of  a  monkey  taken  from  the  gall-bladder 
immediately  after  death  is  dark  green,  but  if  left  a  few  hours  in  the 
gall-bladder  it  is  brown,  the  green  pigment  having  been  reduced.  It 
should  be  remembered  that  human  bile  from  the  post-mortem  room 
may  alter  its  colour  in  the  interval  which  must  elapse  before  it  can 
usually  be  procured  after  death.  Bile,  as  obtained  from  fistula:  in 
otherwise  healthy  persons,  has  a  specific  gravity  of  about  1008  to 
loio.     In  the  gall-bladder  water  is  absorbed   from  the  bile  and 


358 


DIGESTION 


mucin  added  to  it,  so  that  the  specific  gravity  of  bladder  bile  is  as 
high  as  1030  to  1040.     The  reaction  is  feebly  ailkaline  to  litmus. 

The  composition  of  two  specimens  of  human  bile — one  from  a  fistula, 
the  other  from  the  gall-bladder — is  shown  in  the  following  table : 


Bladder  Bile. 

Fistula  Bile. 

Water  -              -              -             -              - 
Solids    -             -             -              -              - 
Mucin  and  other  substances  insoluble 

898-1 

loi-g 

977-4 

22-6 

in  alcohol      -              -              -              - 
Sodium     taurocholate     and     sodium 

14-5 

2-3 

glycocholate                -              -              _ 
Inorganic  salts                _             .             _ 
Fat              ] 

56-5 
6-3 

lO-I 

8-5 

Lecithin       J-     - 
CholesterinJ 

30-9 

0-05 
0-56 

The  substance  which  renders  bladder  bile  viscid,  but  which  is  present 
in  much  smaller  amount  in  bile  from  a  fistula,  and  is  probably  entirely 
absent  from  tlie  fluid  as  it  is  secreted  by  the  liver-cells,  is  commonly 
termed  'mucin.'  It  has  been  shown,  however,  that  in  many  animals — 
for  example,  the  ox,  dog,  sheep,  etc. — the  substance  is  not  a  true  mucin. 
It  does  not  yield,  like  mucin,  on  boiling  with  dilute  acid,  a  carbo- 
hydrate group  (viz.,  glucosamine,  CeHnOjNHa,  correspDnding  to 
dextrose  in  which  OH  is  replaced  by  NH2) .  It  is  relatively  rich  in  phos- 
phorus, and  consists — mainly,  at  any  rate — of  a  phospho-protein  (p.  2). 
The  mucilaginous  substance  of  human  bile  consists  largely  of  true  mucin. 

Mucin  is  scarcely  to  be  looked  upon  as  an  essential  constituent  of 
bile ;  it  is  not  formed  by  the  actual  bile-secreting  cells,  but  by  mucous 
glands  in  the  walls  and  goblet-cells  in  the  epithelial  lining  of  the  larger 
bile-ducts,  and  especially  of  the  gall-bladder. 

Bile-Pigments. — It  has  been  said  that  these  form  a  series,  but  only 
two  of  the  pigments  of  that  series  are  present  in  normal  bile,  bilirubin, 
and  biliverdin.  In  human  bile,  the  former,  in  herbivorous  bile  and 
that  of  some  cold-blooded  animals,  such  as  the  frog,  the  latter  is  the 
chief  pigment.  But  bilirubin  can  be  extracted  in  large  amount  from 
the  gall-stones  of  cattle ;  while  the  placenta  of  the  bitch  contains  bili- 
verdin in  quantity,  although,  as  in  all  carnivora,  it  is  either  absent 
from  the  bile  or  exists  in  it  in  comparatively  small  amount.  These 
facts  show  that  the  two  pigments  are  readily  interchangeable,  but  there 
is  no  question  that  bilirubin  is  the  pigment  which  is  formed  by  the 
liver-cells. 

Bilirubin  (C32H3gN406)  can  be  prepared  from  powdered  red  gall- 
stones by  dissolving  the  chalk  with  hydrochloric  acid,  and  extracting 
the  residue  with  chloroform,  which  takes  up  the  pigment.  From  this 
solution,  on  evaporation,  or  from  hot  dimethyl  anilin,  beautiful  rhombic 
tables  or  prisms  of  bilirubin  separate  out. 

Biliverdin  (C32H3(.N408)  can  be  obtained  from  the  placenta  of  the 
bitch  by  extraction  with  alcohol.  It  is  insoluble  in  chloroform,  and  by 
means  of  this  properly  it  may  be  separated  from  bilirubin  when  the  two 
happen  to  be  present  together  in  bile.  Biliverdin  can  also  be  formed 
from  bilirubin  by  oxidation.     By  the  aid  of  active  oxidizing  agents, 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  359 

sucli  as  yellow  nitric  acid  (which  contains  some  nitrous  acid),  a  whole 
series  of  oxidation  products  of  bilirubin  is  obtained,  beginning  with 
biliverdin,  and  passing  through  bilicyanin,  a  blue  pigment,  and  other 
intermediate  bodies,  to  choletclin,  a  yellow  substance.  It  is  question- 
able whether  these  are  all  definite  compounds.  This  is  the  foundation 
of  Gmelin's  test  for  bile-pigments  (see  Practical  Exercises,  p.  456).  The 
same  colours  arc  produced,  and  in  the  same  order,  when  a  solution  of 
bilirubin  in  chloroform  is  treated  with  a  dilute  alcoholic  solution  of  iodine. 

The  positive  pole  of  a  galvanic  current  causes  the  same  oxidative 
changes,  the  same  play  of  colours,  while  the  reducing  action  of  the 
negative  pole  reverses  the  effect,  if  the  action  of  the  positive  electrode 
has  not  gone  too  far.  These  reactions  can  also  be  used  for  the  detection 
of  bile -pigments. 

By  the  reducing  action  of  sodium  amalgam  on  bilirubin,  hemi- 
bilirubin  (C:};3H44N40b)  is  obtained.  It  gives  a  beautiful  red  colour  with 
^-dimctliylaniinobenzaldehyde  (Ehrlich's  reaction).  Hemibilirubin  is 
identical  with  the  urobilinogen  of  urine  from  which  urobilin  is  derived. 
Urobilinogen  and  urobilin  (often  called  in  this  connection  stercobilin) 
are  also  found  in  the  faeces  from  birth  onwards,  although  not  in  the 
meconium  (p.  418).  Urobilinogen  is  derived  from  the  normal  bile- 
pigment  by  reduction  in  the  intestine  itself,  where  reducing  substances 
due  to  the  action  of  micro-organisms  are  never  absent  in  extra-uterine  life. 

The  bile  of  most  animals  shows  no  characteristic  absorption  spectrum. 
But  the  fresh  bile  of  certain  animals,  the  ox,  for  instance,  does  show 
bands.  These,  however,  are  not  due  to  the  normal  bile-pigment,  and 
they  are  not  essentially  changed  when  this  is  oxidized  or  reduced  by 
electrolysis.  MacMunn  attributes  the  spectrum  of  the  bile  of  the  ox 
and  sheep  to  a  body  which  he  calls  cholohsematin,  and  which  does  not 
belong  to  the  bile-pigments  proper. 

The  Bile-Salts. — These  are  the  sodium  salts  of  certain  acids,  of  which 
glycocholic  and  taurocholic  are  the  chief.  In  the  bile  of  omnivora, 
including  man,  both  are  in  general  present,  and  in  various  proportions; 
in  human  bile  there  is  more  glycocholic  than  taurocholic  acid ;  some- 
times taurocholic  acid  is  entirely  absent.  In  the  bile  of  many  camivora 
— e.g.,  the  dog  and  cat — only  taurocholic  acid  is  found;  in  that  of  the 
camivora  generally  it  is  by  far  the  more  important  of  the  two  acids. 
In  the  bile  of  most  herbivora  there  is  much  more  glycocholic  than 
taurocholic  acid.  The  bile  acids  are  paired  acids:  glycocholic  acid 
(better  named  cholyl-glycin)  formed  by  the  union  of  glycin  and  cholic 
acid,  and  taurocholic  acid  (or  cholyl-taurin),  consisting  of  cholic  acid 
united  with  taurin. 

The  decomposition  of  the  bile-acids  into  these  substances  is  effected 
by  boiling  them  with  dilute  acid  or  alkali,  a  molecule  of  water  being 
taken  up;  thus — 

C26H43NO6  +  H2O  =  CH2  (NH2)  .COOH  +  C24H40O5 ; 

Glycocholic  acid.  Glycin.  Cholic  acid. 

C2CH45NSO7  +  H20=  CH2(NH2)  .CH2.SO2.OH  +  C24H40O5. 

Taurocholic  acid.  Taurin.  Cholic  acid. 

A  notable  difference  between  glycocholic  and  taurocholic  acid  is  that 
the  latter  contains  sulphur.  The  whole  of  this  belongs  to  the  taurin. 
Both  glycin  and  taurin  are  derived  from  the  disintegration  of  proteins. 
We  have  already  seen  that  among  the  products  of  protein  hydrolysis  a 
sulphur-containing  body,  cystein,  which  is  readily  changed  into  cystin, 
is  found,  and  Ihere  is  good  evidence  that  taurin  is  derived  from  cystein 


36o  DIGESTION 

or  cystin.  In  certain  pathological  conditions  cystin  appears  in  the 
urine  (cystinuria).  The  source  of  the  cholic  acid  which  goes  to  form 
the  bile  acids  is  unknown,  but  it  has  been  surmised  that  it  may  be 
derived  from  cholesterin.     Thus, 

[CH2.SH  +  30     CHo.SOa.OH     CHo.SOg.OH 

'I  I    ■  i 

CH.NH2    =     CH.NH2     =     CH.NH2 

I  I 

COOH  COOH— CO2 

Cystein.  Cysteinic  acid.  Taurin. 

Traces  of  cholic  acid,  formed  by  hydrolysis  from  the  bile-acids  by 
the  action  of  putrefactive  bacteria,  are  found  in  the  intestines,  especially 
in  the  lower  portion. 

Pettenkflfer' s  test  for  bile-acids  (Practical  Exercises,  p.  456),  acciden- 
tally discovered  in  examining  the  action  of  bile  upon  sugar,  depends  upon 
three  facts:  (i)  That  cholic  acid  and  furfuraldehyde  giv-e  a  purple  colour 
when  brought  together;  (2)  that  the  bile-salts  yield  cholic  acid  when 
acted  upon  by  sulphuric  acid ;  (3)  that  when  cane-sugar  is  decomposed 
by  strong  sulphuric  acid,  furfuraldehyde  is  formed. 

Since  a  similar  colour  is  given  when  the  same  reagents  are  added  to  a 
solution  containing  albumin,  it  is  necessary  to  remove  this,  if  present, 
from  any  liquid  which  is  to  be  tested  for  bile -acids. 

Lecithin  and  cholesterin,  or  cholesterol .  are  by  no  means  peculiar  to 
bile  (p.  4).  They  are  very  widely  distributed  in  the  body.  lecithin 
(C44H90NPO9)  belongs  to  the  group  of  phosphatides,  fat-like  phosphorus- 
containing  substances  present  in  all  cells.  It  is  a  compound  of  glycerin 
with  two  molecules  of  fatty  acid  and  one  of  phosphoric  acid.  The 
phosphoric  acid  is  at  the  same  time  united  with  a  base  cholin  (C5H15NO2). 
The  fatty  acid  (stearic,  palmitic,  oleic,  etc.)  varies  in  different  varieties 
of  lecithin .  Heated  with  baryta-water,  lecithin  yields  the  corresponding 
fatty  acid  in  the  form  of  a  soap,  along  with  cholin  and  glyccryd-phos- 
phoric  acid.  Glyceryl-phosphoric  acid  can  be  further  split  so  as  to 
yield  a  molecule  of  glvcerin  and  one  of  phosphoric  acid. 

Cholesterin  is  a  substance  with  the  empirical  formula  C27H46O.  It 
contains  an  alcohol  group  in  virtue  of  which  fatty  acids  can  be  linked 
to  it,  forming  esters.  It  is  best  obtained  from  white  gall-stones,  of 
which  it  is  the  chief,  and  sometimes  almost  the  sole  constituent  (see 
Practical  Exercises,  p,  457). 

All  the  compounds  related  to  cholesterin  are  grouped  together  under 
the  name  of  sterins.  The  stcrins  are  very  widely  distributed  both  in 
animals  (zoosterins)  and  in  plants  (ph3i;osterins).  Ever\'  cell  seems  to 
contain  sterins  and  sterin  esters  (compounds  of  the  same  nature  a.s  the 
compounds  of  fattv  acids  with  the  alcohol  glycerin  which  constitute  the 
neutral  fats) .  In  the  vertebrates  cholesterin  and  its  product?  co.istitute 
the  chief,  perhaps  the  only  sterins,  but  in  invertebrate  animals  and 
plants  there  is  a  much  greater  variety  of  these  substances. 

The  chief  inorganic  salts  of  bile  are  sodium  chloride,  sodium  carbonate, 
and  alkaline  sodium  phosphate.  The  phosphoric  acid  of  the  ash  comes 
partly  from  the  phosphorus  of  organic  compounds  (lecithin  and  bile- 
mucin),  the  sulphuric  acid  from  the  sulphur  of  taurocholic  acid,  the 
sodium  largely  from  the  bile-salts.  Iron  is  a  notable  inorganic  con- 
stituent of  bile,  although  it  exists  only  in  traces,  in  the  form  of  phosphate 
of  iron.  Manganese  is  also  present  in  minute  amount.  100  c.c.  of 
fresh  bile  yields  50  to  100  c.c.  of  carbon  dioxide,  part  of  which  is  in 
solution  and  part  combined  with  alkalies. 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  361 

The  quantity  of  bile  secreted  in  twenty-four  hours  in  an  averaee 
man  is  probably  from  750  c.c.  to  a  litre.  In  nine  cases  of  fistula  of 
the  gall-bladder  in  patients  operated  on  for  gall-stones  or  echino- 
coccus  the  daily  quantity  varied  from  500  to  1,100  cc  (Brand). 

Digestive  Functions  of  Bile. — The  great  action  of  the  bile  in 
digestion  is  undoubtedly  the  preparation  of  the  fats  for  absorption. 
In  this  preparation  four  processes  are  important:  two  chemical 
actions,  hydrolysis  of  neutral  fats  to  glycerin  and  fatty  acids,  and 
saponification,  or  the  formation  of  soaps  by  the  union  of  fatty  acids 
with  bases,  especially  sodium ;  and  two  physical  processes,  emulsifi- 
cation,  or  the  formation  of  a  mechanical  suspension  of  such  fine 
globules  of  unaltered  neutral  fat  as  exist  in  milk,  and  solution  of 
soaps  and  fatty  acids.  While  there  has  been  much  discussion  as  to 
the  relative  share  taken  by  these  processes,  and  especially  by  saponi- 
fication and  emulsification  in  the  absorption  of  fat  (p..  435),  there  is 
no  doubt  that  they  are  all  concerned  in  the  digestion  of  fat  or  the 
preparation  of  it  for  absorption  and  assimilation.  In  this,  indeed, 
the  processes  are  complementary  to  each  other,  for  an  essential  pre- 
liminary to  emulsification  in  the  intestine  seems  to  be  the  formation 
of  a  certain  amount  of  soaps,  soluble  in  the  intestinal  contents,  while 
the  formation  of  an  emulsion  enormously  increases  the  surface  of 
contact  between  the  unaltered  fat  and  the  digestive  juices,  and  so 
favours  more  rapid  hydrolysis,  saponification,  and  solution.  In  the 
whole  series  of  changes  the  bile  plays  a  part,  though  not  an  indepen- 
dent one;  it  acts  always  in  conjunction  with  the  pancreatic  juice. 

While  no  complete  explanation  has  been  given  of  the  precise 
nature  of  this  partnership,  it  is  certain  that  the  fat-splitting  ferment 
of  the  pancreatic  juice  on  the  one  hand,  and  the  bile-salts  on  the 
other,  contribute  largely  to  the  total  action.  An  alkaline  solution, 
a  solution  of  sodium  carbonate,  e.g.,  is  unable  of  itself  to  emulsify 
a  perfectly  neutral  oil ;  but  if  some  free  fatty  acid  be  added,  emulsifi- 
cation is  rapid  and  complete  (p.  12).  Now,  there  is  no  doubt  that 
here  a  soap  is  formed  by  the  action  of  the  alkali  on  the  fatty  acid, 
and  there  is  equally  little  doubt  that  the  formation  of  the  soap  is  an 
essential  part  of  the  emulsification.  But  it  is  not  clear  in  what 
manner  the  soap  acts,  whether  by  forming  a  coating  round  the  oil- 
globules,  or  by  so  altering  the  surface-tension,  or  other  physical 
properties  of  the  solution  in  which  it  is  dissolved,  that  they  no  longer 
tend  to  run  together.  However  this  may  be,  in  pancreatic  juice  we 
have  the  two  factors  present  which  this  simple  experiment  shows 
to  be  necessary  and  sufiicient  for  emulsification  ;  we  have  a  ferment 
which  can  split  up  neutral  fats  and  set  free  fatty  acids,  and  an  alkali 
which  can  combine  with  those  acids  to  form  soaps.  Accordingly, 
pancreatic  juice  is  able  of  itself  to  form  emulsions  with  perfectly 
neutral  oils.  It  is  possible  that  the  protein  constituents  of  pancreatic 
juice  may  have  a  share  in  emulsification,  since  the  addition  of  protein 


362  DIGESTION 

— e.g.,  egg-white — to  a  soap  solution  increases  the  stabihty  of  the 
emulsions  formed  by  the  soap.  In  bile,  on  the  contrary,  although 
the  alkali  is  present,  there  is  no  fat-splitting  ferment,  and,  according 
to  the  best  experiments,  bile  alone  has  no  emulsifying  power  75n 
perfectly  neutral  fat.  But  we  now  come  to  a  remarkable  fact:  this 
inert  bile  when  added  to  pancreatic  juice  greatly  intensifies  its 
emulsifying  action,  and  a  solution  of  bile-salts  has  much  the  same 
effect  as  bile  itself.  The  fact  is  undoubted,  but  the  explanation  is 
obscure.  What  it  is  that  the  bile  or  bile-salts  can  add  to  the 
pancreatic  juice  which  so  increases  its  power  of  emulsification,  we  do 
not  know.  It  has  been  surmised  that  a  characteristic  physical 
property  of  bile,  the  diminution  of  the  surface-tension  of  watery 
liquids  to  which  it  is  added,  may  play  an  important  part,  perhaps, 
in  enabling  the  fat-splitting  ferments  or  the  emulsifying  soaps  to  get 
into  closer  contact  with  the  unaltered  fat.  It  is  also  true  that 
bile,  presumably  in  virtue  of  the  chemical  action  of  its  alkaline 
salts,  can,  in  presence  of  a  free  fatty  acid,  rapidly  form  an  emulsion. 
But  the  pancreatic  juice  itself  contains  so  considerable  a  quantity  of 
sodium  carbonate  that  it  would  scarcely  seem  to  require  the  rela- 
tively feeble  reinforcement  of  the  alkaline  salts  of  the  bile. 

An  important  part  of  the  effect  of  the  bile  is  certainly  due  to  its 
favouring  the  fat-splitting  action  of  the  pancreatic  juice.  By  the 
addition  of  bile,  the  quantity  of  fat  split  up  by  a  definite  amount  of 
dog's  pancreatic  juice  may  be  increased  two  to  threefold.  It  has 
been  shown  that  this  is  an  action  of  the  bile-salts.  The  sodium 
salts  of  synthetically-obtained  glycocholic  and  taurocholic  acids 
produce  the  same  effect.  It  is  in  virtue  of  this  action  that  the  bile- 
salts  are  sometimes  spoken  of  as  the  co-ferment  of  the  lipase.  As 
already  pointed  out,  this  action  is  exerted  in  presence  of  the  fully 
formed  enzyme,  and  should  not  be  confounded  with  the  effect  of  the 
bile-salts  in  activating  the  lipase  zymogen.  The  capacity  of  dis- 
solving soaps,  which  is  a  property  of  the  bile-salts,  is  also  of  great 
importance  in  supplementing  the  solvent  power  of  the  intestinal 
liquids  for  the  products  formed  by  the  pancreatic  juice.  The 
solution  of  soaps  in  the  bile-salts  has  the  power  in  its  turn  of  dis- 
solving free  fatty  acids.  The  significance  of  this  in  fat  absorption 
will  be  referred  to  again.  A  further  illustration  of  the  mutual 
adaptation  of  the  various  digestive  juices,  of  the  remarkably  precise 
manner  in  which  the  action  of  each  dovetails  into  the  action  of 
others,  is  afforded  by  the  facts  already  mentioned  in  connection  with 
the  lipase  of  the  stomach.  It  is  highly  probable  that  the  fatty  acids 
formed  by  the  gastric  lipase,  even  if  formed  only  in  small  amount, 
may  exertan  important  influence  in  emulsifying  the  fat  as  soon  as  it 
enters  the  intestine.  The  intestinal  juice  itself  also  unquestionably 
takes  a  share  in  the  digestion  of  fat  along  with  the  pancreatic 
secretion  and  the  bile.     There  exists  also,  as  will  be  seen  later  on,  a 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  363 

certain  adaptation  between  the  food  and  the  digestive  secretions. 
Not  the  best  illustration  of  this,  but  one  which  suits  the  present  topic, 
is  the  fact  that  the  food  itself  probably  always  contains  some  free 
fatty  acids  when  it  contains  fat  at  all.  Although  our  knowledge  of 
the  mutual  action  of  the  pancreatic  juice  and  the  bile  on  the  digestion 
of  fats  is  still  incomplete,  there  is  no  doubt  that  they  are  equally 
necessary.  For  in  some  diseases  of  the  pancreas  fat  or  fatty  acid 
often  appears  in  the  stools,  and  this  token  of  imperfect  digestion  of 
the  fatty  food  may  be  confirmed  b}'  the  wasting  of  the  patient.  The 
same  may  occur  when  the  bile  is  prevented  by  obstruction  of  the 
duct  or  by  a  biliary  fistula  from  entering  the  intestine.  Yet  in  some 
cases  of  fistula,  where  there  is  every  reason  to  believe  that  all  the  bile 
is  escaping  externally,  the  nutrition  of  the  patient — at  any  rate,  on  a 
diet  not  abnormally  rich  in  fat — is  unaffected.  The  mere  deficiency 
of  bile  in  the  intestine  is,  of  course,  complicated  in  obstructive 
jaundice  by  the  harmful  effects  of  the  bihary  constituents  circulating 
in  the  blood. 

The  white  stools  of  jaundice  owe  their  colour,  not  merely  to  the 
absence  of  bile-pigment,  but  also  to  the  presence  of  fat.  Their  highly 
offensive  odour  used  to  be  adduced  as  evidence  that  bile  is  the  '  natural 
antiseptic  '  of  the  intestine.  It  seems  rather  to  be  due  to  the  coating 
of  the  particles  of  food  with  undigested  fat,  which  shields  the  proteins 
from  the  action  of  the  digestive  juices,  while  permitting  the  putrefactive 
bacteria  to  revel  in  them  unchecked.  As  a  matter  of  fact,  the  bile 
itself  has  little,  if  any,  power  of  hindering  the  growth  of  micro-organisms, 
although  the  free  bile-acids  are  tolerably  active  antiseptics.  In  suckling 
children  it  is  not  uncommon  to  see  the  faeces  white  with  fat.  This  is  a 
less  serious  s^inptom  than  in  adults,  and  perhaps  betokens  merely  that 
the  milk  in  the  feeding-bottle  is  undiluted  cow's  milk,  which  is  richer 
in  fat  than  human  milk,  and  ought  to  be  mixed  with  water. 

Bidder  and  Schmidt  found  that  the  chyle  in  the  thoracic  duct  of  a 
normal  dog  contained  3-2  per  cent,  of  fat.  In  a  dog  with  the  bile-duct 
ligatured  the  proportion  fell  to  0-2  per  cent.  It  is  an  instance  of  the 
extraordinarily  exact  adaptation  of  the  digestive  juices  to  the  nature 
of  the  food,  the  mechanism  of  which  will  present  itself  for  discussion 
later  on,  that  the  reinforcing  action  of  the  bile  upon  the  fat-splitting 
ferment  of  the  pancreatic  juice  is  said  to  be  greater  when  the  food  is 
rich  in  fat  (p.  408). 

Bile  has  been  credited  with  a  physical  power  of  aiding  the  passage 
of  fat  through  membranes  moistened  with  it  by  diminishing  the  surface 
tension,  and  it  has  been  inferred  that  this  has  an  important  bearing 
on  the  absorption  of  fat  from  the  intestine.  But  the  inference  docs 
not  follow  from  the  statement,  and  the  statement  has  been  itself 
denied.  There  is  at  present  no  evidence  that  the  digestive  function 
of  the  bile  extends  beyond  the  preparation  of  the  food  for  absorption 
to  the  preparation  of  the  mucosa  for  absorbing  it. 

On  proteins  bile  has  either  no  digestive  action,  or  only  a  feeble 
one.  Fibrin  is  slightly  digested  by  the  bile  of  the  dog  and  of  man. 
But  the  addition  of  it  to  fresh  pancreatic  juice  considerably  increases 
the  proteolytic  power  of  that  secretion  (Rachford),  although  not  so 
decidedly  as  in  the  case  of  the  fat-splitting  action.     The  amylohi:ic 


364  DIGESTION 

action  of  the  pancreatic  juice  is  also  favoured  by  the  bile,  and  in 
about  the  same  degree  as  its  proteol>i:ic  effect.  Although  bile  some- 
times exerts  by  itself  a  feebly  amylol}i:ic  action,  this  is  not  to  be 
included  among  its  specific  powers,  for  a  diastatic  ferment  in  small 
quantities  is  \videly  diffused  in  the  body. 

The  addition  of  bile  or  bile-salts  to  a  gastric  digest  causes  the 
precipitation  of  any  unaltered  native  protein,  acid-albumin,  albu- 
mose,  and  pepsin.  The  precipitate,  which  is  a  salt-hke  compound 
of  protein  with  taurochohc  acid,  is  redissolved  when  the  liquid  is 
rendered  alkahne,  and  therefore  in  excess  of  bile,  or  of  a  solution  of 
bile-salts,  but  the  pepsin  has  no  longer  any  power  of  digesting 
proteins.  Part  of  the  bile-acids  and  bile-mucin  is  also  thrown  down 
by  the  acid  of  the  digest.  It  has  been  suggested  that  by  thus 
precipitating  the  constituents  of  the  chyme  which  have  not  been 
carried  to  the  peptone  stage  bile  prepares  them  for  the  action  of  the 
pancreatic  juice.  But  it  is  difficult  to  see  how  the  precipitation  of 
a  substance  can  prepare  the  way  for  its  digestion,  and  it  is  more 
probable  that  if  any  physiological  value  is  to  be  given  to  this  reaction, 
it  has  the  function  of  preventing  the  absorption  of  proteins  which 
have  not  been  sufficiently  split  up.  There  is  little  doubt,  however, 
that  the  rendering  of  the  pepsin  inactive  has  physiological  signifi- 
cance, for  pepsin  exerts  an  injurious  influence  upon  the  ferments  of 
the  pancreatic  juice.  In  digestion,  then,  the  bile  has  a  twofold  func- 
tion, favouring  greatly  the  activity  of  the  pancreatic  ferments,  especially 
the  fat-splitting  ferment,  and  aiding  in  establishing  the  conditions 
necessary  for  the  transition  of  gastric  into  intestinal  digestion. 

Succus  Entericus. — This  is  the  name  given  to  the  special  secretion 
of  the  small  intestine,  which  is  supposed  to  be  a  product  of  the 
Lieberkiihn's  crypts  or  intestinal  glands.  In  order  to  obtain  it  pure, 
it  is  of  course  necessary  to  prevent  admixture  with  the  bile,  the  pan- 
creatic juice,  and  the  food.  This  can  be  done  by  dividing  a  loop  of 
intestine  from  the  rest  by  two  transverse  cuts,  the  abdomen  having 
been  opened  in  the  linea  alba.  The  continuity  of  the  digestive  tube 
is  restored  by  stitching  the  portion  below  the  isolated  loop  to  the 
part  above  it.  One  end  of  the  loop  is  sewed  into  the  lips  of  the 
wound  in  the  linea  alba,  and  the  other  being  closed  by  sutures,  the 
whole  forms  a  sort  of  test-tube  opening  externally  (Thiry's  fistula). 
Or  both  ends  are  made  to  open  through  the  abdominal  wound  ( Vella's 
fistula).  Another  method  is  to  make  a  single  opening  in  the  intes- 
tine, and  by  means  of  two  indiarubber  balls,  one  of  which  is  pushed 
down,  and  the  other  up  through  the  opening,  and  which  are  after- 
wards inflated,  to  block  off  a  piece  of  gut  from  communication  with 
the  rest.  Or  several  openings  may  be  made  at  different  levels  in  the 
intestine,  each  being  allowed  to  heal  into  a  wound  in  the  abdominal 
wall.  When  pure  juice  is  required  it  is  collected  from  the  lower 
fistulae,  while  the  upper  fistulae  are  opened  to  permit  the  escape  of  the 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  365 

secretions  which  enter  the  higher  portions  of  the  ahmentary  canal 
(gastric  juice,  pancreatic  juice,  and  bile).  The  intestinal  juice  so 
obtained  is  a  thin  yellowish  liquid  of  alkaline  reaction,  generally 
somewhat  turbid  from  the  presence  of  a  certain  number  of  leucocytes 
and  epithelial  cells.  Its  specific  gravity  is  about  loio,  the  total 
solids  about  1-5  per  cent.  It  contains  a  small  amount  of  proteins, 
including  serum  albumin  and  serum  globuHn,  and  about  the  same 
proportion  of  inorganic  salts  as  most  of  the  liquids  and  solids  of  the 
body,  namely,  07  or  o-8  per  cent.,  chiefly  sodium  carbonate  and 
sodium  chloride;  but,  like  the  other  digestive  liquids,  it  is  adapted 
to  the  nature  of  the  food,  and  therefore  its  composition  is  not  quite 
constant.  Like  bile,  intestinal  juice  acts  but  feebly  on  the  food 
substances  by  itself,  and  if  we  contented  ourselves  with  examining 
the  pure  and  isolated  secretion,  we  should  greatly  underestimate  its 
importance.  The  sodium  carbonate,  in  which  it  is  relatively  rich, 
will,  to  be  sure,  form  soaps  with  fatty  acids  produced  by  the  action 
of  the  pancreatic  juice  or  of  the  fat-splitting  bacteria  in  which  the 
intestine  abounds,  and  thus  aid  in  the  digestion  of  fats.  A  lipase, 
feebler  than  that  of  the  pancreatic  juice,  or  present  in  smaller  con- 
centration, is  also  a  constituent  of  the  succus  entericus.  That  a 
great  deal  of  fat  may  be  split  up  in  the  alimentary  canal  in  the 
absence  both  of  bile  and  pancreatic  juice  is  well  ascertained.  The 
alkali  of  the  succus  entericus  must  at  the  same  time  aid  in  neutraliz- 
ing the  original  acidity  of  the  chyme,  and  in  preserving  the  proper 
reaction  of  the  intestinal  contents.  A  ferment  called  invertase,  or 
sucrase — which  is  not  introduced  with  the  food  or  formed  by  bacterial 
action  as  has  been  suggested,  since  it  occurs  in  the  aseptic  intestine 
of  the  nev/-born  child — will  invert  cane-sugar.  The  ferments  maltase 
and  lactase  will  cause  a  corresponding  change  in  maltose  and  lactose 
(see  footnote,  p.  350).  It  is  worthy  of  remark  that  these  inverting 
enzymes  are  present  in  the  intestinal  mucosa  as  well  as  in  the 
intestinal  juice,  and  extracts  of  the  mucosa  are  usually  distinctly 
more  active  than  the  juice  itself.  So  that  there  is  reason  to  believe 
that  hydrolysis  of  the  disaccharides  may  take  place  both  in  the 
lumen  of  the  gut  before  absorption  and  in  the  wall  of  the  gut  during 
absorption.  Inverting  enzymes  appear  in  the  intestine  early  in 
embryonic  life.  Maltase  is  the  most  generally  distributed  of  all 
these  enzymes,  and  it  is  found  along  with  lactase  in  the  intestine  of 
the  embryo  pig,  while  invertase  is  missing  till  after  birth  (Mendel). 
On  native  proteins  and  starch  the  isolated  succus  entericus  has  little 
or  no  action.  But  it  contains  a  ferment,  erepsin,  which,  although  it 
does  not  affect  native  proteins  Hke  serum-  and  egg-albumin  (fibrin 
and  caseinogen  may  be  slightly  digested),  exerts  a  powerful  action 
on  the  first  products  of  protein  hydrolysis,  albumoses,  and  peptones, 
breaking  them  up  into  bodies  which  no  longer  give  the  biuret  re- 
action   (ammonia,    mono-amino    acids,    hexone    bases,    etc.).     It 


366  DIGESTION 

destroys  the  diphtheria  toxin,  which  is  also  rendered  innocuous  by 
trypsin.  Erepsin,  however,  is  not  specific  to  the  secreted  intestinal 
juice,  for  it  occurs  also,  not  only  in  the  mucous  membrane  of  the 
intestine,  which,  indeed,  contains  a  greater  quantity  of  it  than  the 
succus  entericus,  but  in  all  animal  tissues  hitherto  investigated.  It 
is  said  even  to  be  sometimes  present  in  pancreatic  juice,  since  in- 
activated pancreatic  juice,  which  does  not  digest  other  proteins,  will 
sometimes  digest  casein.  But  the  matter  is  far  from  being  settled, 
and  the  presence  of  erepsin  in  the  pancreatic  tissue  is  a  complicating 
circumstance.  For  under  abnormal  conditions,  most  glands  pro- 
vided with  artificial  fistulae  have  an  increased  hability  to  injuries 
of  various  kinds,  which  might  permit  constituents  not  normally 
present  in  the  secretion  to  pass  into  it  from  the  cells.  The  kidney  in 
mammals  is  even  richer  in  erepsin  than  the  intestinal  mucous 
membrane.  Next  to  these  come  the  pancreas,  spleen,  and  liver, 
then  at  a  long  interval  the  heart  muscle,  while  skeletal  muscle  and 
brain-tissue  are  poorest  of  all  in  the  ferment.  The  intestinal  mucosa 
varies  in  its  erepsin  content  at  different  levels  and  on  different  diets. 
In  cats  on  a  meat  or  a  mixed  diet  the  duodenum  is  about  five  times 
richer  in  the  ferment  than  the  stomach.  The  ileum  is  about  half  as 
rich  as  the  duodenum,  and  the  jejunum  occupies  an  intermediate 
position  between  the  duodenum  and  ileum  (Vernon).  The  secretion 
of  Brunner's  glands  in  the  duodenum,  which  resemble  in  structure 
the  pyloric  glands  of  the  stomach,  digests  coagulated  albumin, 
although  its  proteolytic  powers  are  feebler  than  those  of  the  pan- 
creatic juice. 

Enterokinase. — The  most  characteristic  constituent  of  succus 
entericus  is  a  ferment,  enterokinase,  which  differs  from  all  the  fer- 
ments we  have  hitherto  described  in  acting  not  directly  upon  the 
foodstuffs,  but  upon  the  trypsinogen  of  the  pancreatic  juice,  chang- 
ing it  into  the  active  enzyme  trypsin.  It  may  therefore  be  spoken  of 
as  a  ferment  of  ferments.  It  has  been  previously  stated  that  freshly 
secreted  pancreatic  juice  is  without  action  upon  proteins.  The 
addition  of  succus  entericus  immediately  confers  upon  it  a  high 
degree  of  proteolytic  power.  In  one  experiment  pancreatic  juice, 
obtained  by  a  temporary  fistula,  required  four  to  six  hours  to  dissolve 
fibrin,  and  did  not  attack  coagulated  albumin  even  in  ten  hours. 
On  addition  of  succus  entericus,  the  same  pancreatic  juice  dissolved 
fibrin  in  three  to  seven  minutes,  and  rapidly  digested  coagulated 
albumin  (Pawlow).  In  like  manner  a  glycerin  extract  of  a  fresh 
pancreas  has  hardly  any  effect  on  proteins;  a  similar  extract  of  a 
stale  pancreas  is  active.  The  fresh  pancreas  contains  trypsinogen, 
which  is  soluble  in  glycerin,  for  the  inert  extract  becomes  active 
when  it  is  treated  with  dilute  acetic  acid,  or  even  when  it  is  diluted 
with  water  and  kept  at  the  body-temperature.  If  the  fresh  pancreas 
be  first  treated  with  dilute  acetic  acid,  and  then  with  glycerin,  the 


THE  CHEMISTRY  OF  THE  DIGESTIVE  JUICES  367 

extract  is  at  once  active.  The  trypsinogen  can  therefore  be  activated 
within  the  pancreatic  cells,  gradually  when  the  pancreas  is  simply 
allowed  to  stand  after  excision,  more  rapidly  in  presence  of  the  dilute 
acid.  The  ordinary  tests  for  ferment  action  (destruction  by  boiling, 
activity  in  very  small  amounts,  etc.)  have  shown  that  this  property 
of  the  intestinal  juice  is  due  to  a  ferment,  although  it  differs  in 
certain  respects  from  most  ferments — for  instance,  in  requiring  a 
relatively  high  temperature  to  inactivate  it.  The  smallest* trace 
of  entcrokinase  will  convert  a  large  quantity  of  trypsinogen  into 
trypsin  if  time  be  given.  At  the  same  time,  although  to  a  much 
smaller  extent,  the  fat-splitting  and  starch-digesting  activity  of  the 
pancreatic  juice  is  increased.  The  secretion  of  the  duodenum  causes 
a  greater  increase  in  the  proteol3i:ic  power  than  that  of  the  other 
portions  of  the  small  intestine,  while  no  such  difference  has  been 
made  out  in  the  case  of  the  amylolytic  and  Hpolytic  functions.  It  is 
probable  that  the  entcrokinase,  which  is  secreted  mainly  in  the  upper 
two -sevenths  of  the  small  intestine,  and  solely  by  the  intestinal 
epithelium,  acts  only  on  the  trypsinogen,  and  that  the  am^'lopsin 
and  steapsin  are  aided  in  some  other  way.  Entcrokinase  is  only 
found  in  the  intestinal  juice  when  pancreatic  juice  is  present  in  the 
gut.  It  is  therefore  secreted  in  response  to  the  presence  of  tryp- 
sinogen or  of  some  other  constituent  of  the  pancreatic  juice. 

Delezenne  has  attempted  to  explain  the  interaction  of  enterokinase 
and  trypsinogen  as  an  adaptive  phenomenon  of  the  same  kind  as  the 
formation  of  antitoxins  and  hecmolysins  (p.  31).  According  to  him, 
entcrokinase  acts  hke  a  complement  in  haemolysis,  while  trypsinogen 
plays  the  part  of  an  intermediary  body  or  amboceptor  which  enables 
the  entcrokinase  to  attack  the  protein  molecule.  He  asserts  that 
entcrokinase,  or  a  substance  which  produces  a  similar  effect  on  tryp- 
sinogen, is  contained  not  only  in  the  mucous  membrane  of  the  intestine, 
but  also  in  leucocytes,  in  fibrin  (one  of  whose  properties  it  is  to  pick 
out  ferments  from  liquids  containing  them),  in  lymph-glands,  in  snake 
venom,  and  even  in  certain  anaerobic  bacteria.  On  this  view  trypsin 
would  not  be  a  definite  substance  produced  by  the  interaction  of 
entcrokinase  and  trypsinogen,  but  only  an  expression  for  these  two 
bodies  acting  together.  Strong  evidence  against  this  view,  and  in 
favour  of  the  independent  existence  of  trypsin,  haj  been  brouglit  forward 
by  Bayliss  and  Starling,  and  it  does  not  seem  to  merit  further  con- 
sideration. According  to  Mellanby,  entcrokinase  is  really  a  proteolytic 
ferment,  and  trypsinogen  contains  a  protein  moiety  with  which  trypsin 
is  firmly  combined.  The  conversion  of  trypsinogen  into  trypsin 
depends  on  the  digestion  of  this  protein  moictj-,  and  the  consequent 
liberation  of  trypsin.  Vernon  has  put  forward  the  \iew  that,  while 
entcrokinase  starts  the  activation  of  trypsinogen  in  the  intestine,  and 
can  no  doubt  in  time  complete  it,  the  trypsin  as  it  is  formed  aids  in  the 
activation  of  more  trypsinogen  to  trypsin,  and  so  on  by  a  process  of 
so-called  auto-caxalysis  of  the  trypsinogen.  This  idea  can  be  har- 
monized with  Mellanby 's  conception  by  assuming  that  the  trvpsin 
formed  from  trypsinogen  can  itself  digest  the  protein  moiety  of  a  further 
portion  of  trypsinogen. 


368  DIGESTION 

According  to  Pawlow,  the  reason  why  the  tryps'n  is  not  secreted 
in  the  active  form  is  that  active  trypsin  readily  destroys  the  amylo- 
lytic  and  hpolytic  ferments.  In  the  intestine,  where  trypsin  is 
rendered  active  by  enterokinase,  thes?  ferments  are  protected  from 
its  attack  by  the  proteins  of  the  food  and  by  the  bile.  Enterokinase 
is  itself  immediately  destroyed  in  the  presence  of  free  acid  (centi- 
normal  hydrochloric  acid). 

H»ving  now  finished  our  review  of  the  chemistry  of  the  digestive 
juices,  oiu"  next  task  is  to  describe  what  is  known  as  to  their  secre- 
tion— the  nature  of  the  cells  by  which  it  is  effected  and  their  histo- 
logical appearance  in  activity  and  repose,  and  the  manner  in  which 
it  is  called  forth  and  controlled. 


Section  IV.— The  Secretion  of  the  Digestive  Juices — 
Microscopical  Changes  in  the  Gland  Cells. 

The  digestive  glands  are  formed  originally  from  involutions  of  the 
mucous  membrane  of  the  alimentary  canal,  the  salivary  glands  from 
the  ectoderm,  the  others  from  the  endoderm  (Chap.  XIX.).  Some  are 
simple  unbranchcd  tubes,  in  which  there  is  either  no  distinction  into 
body  and  duct,  as  in  Lieberkiihn's  cn,^pts  in  the  intestines,  or  in  which 
one  or  more  of  the  tubes  open  into  a  duct,  as  in  the  glands  of  the  fundus 
of  the  stomach.  Some  are  branched  tubes,  several  of  which  may  end 
in  a  common  duct ;  such  are  the  glands  of  the  pyloric  end  of  the  stomach 
and  the  Brunner's  glands  in  the  duodenum.  In  others  the  main  duct 
ramifies  into  a  more  or  less  complex  system  of  small  channels,  into  each 
of  the  ultimate  branches  of  which  one  or  more  (usually  several)  of  the 
secreting  tubules  or  alveoli  open.  The  salivary'  glands  and  the  pancreas 
belong  to  this  class  of  compound  tubular  or  racemose  glands,  and  so 
does  the  liver  of  such  animals  as  the  frog.  But  in  the  latter  organ  the 
typical  arrangement  is  obscured  in  the  higher  vertebrates  by  the  pre- 
dominance of  the  portal  bloodvessels  over  the  system  of  bile-channels 
as  a  groundwork  for  the  grouping  of  the  cells. 

In  every  secreting  gland  there  is  a  vascular  plexus  outside  the  cells 
of  the  gland-tubes,  and  a  system  of  collecting  channels  on  their  inner 
surface ;  and  in  a  certain  sense  the  cells  of  every  gland  are  arranged 
with  reference  to  the  bloodvessels  on  the  one  hand,  and  the  ducts  on 
the  other.  But  in  the  ordinary  racemose  gland  the  blood-supply  is 
mainly  required  to  feed  the  secretion  ;  the  cells  of  the  alveoli  have  either 
no  other  function  than  to  secrete,  or  if  they  have  other  functions,  they 
are  not  such  as  to  entail  a  great  disproportion  between  the  size  of  the 
cells  and  the  lumen  of  the  channels  into  which  they  pour  their  products. 
For  both  reasons  the  relation  of  the  grouping  cf  the  cells  to  the  duct- 
system  is  very  obvious,  to  the  blood-sj  stem  very  obscure.  In  the  liver, 
the  conditions  are  precisely  reversed.  We  cannot  suppose  that  the 
manufacture  of  a  quantity  of  bile  less  in  volume  than  the  secretion  of 
the  salivary  glands,  though  doubtless  containing  far  more  solids, 
requires  an  immense  organ  like  the  liver,  and  a  tide  of  blood  like  that 
which  passes  through  the  portal  vein.  And,  as  we  shall  see.  the  liver 
has  other  functions,  some  of  them  certainly  of  at  least  equal  importance 
with  the  secretion  of  bile,  and  one  of  them  evidently  requiring  from 
its  very  nature  a  bulky  organ.  Accordingly,  both  the  richness  of  the 
blood-supply  and  the  size  of  the  secreting  cells  are  out  of  proportion  to 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES  369 

the  calibre  of  the  ultimate  channels  that  carry  the  secretion  away. 
The  so-called  bile-capillaries,  which  represent  the  lumen  of  the  secreting 
tubules,  are  mere  grooves  in  the  surface  of  adjoining  cells;  and  the 
architectural  lines  on  which  the  liver  lobule  is  built  are:  (i)  the  inter- 
lobular veins  which  carry  blood  to  it;  (2)  the  rich  capillary  network 
which  separates  its  cells  and  feeds  them;  and  (3)  the  central  intra- 
lobular vein  which  drains  it.  Thus  a  network  of  cells  lying  in  the 
meshes  of  a  network  of  blood-capillaries  takes  the  place  of  a  regular 
dendritic  arrangement  of  ducts  and  tubules;  and  in  accordance  with 
this  the  bile-capillaries,  instead  of  opening  separately  into  the  ducts, 
form  a  plexus  with  each  other  within  the  hepatic  lobule  (see  also  foot- 
note, p.  14). 

The  ducts  and  secreting  tubules  of  all  glands  are  lined  by  cells  of 
columnar  epithelial  type,  but  the  type  is  most  closely  preserved  in  the 
ducts.  In  none  of  the  digestive  glands  is  there  more  than  a  single 
complete  layer  of  secreting  cells.  But  the  alveoli  of  the  mucous 
salivary  glands  show  here  and  there  a  crescent-shaped  group  of  small 
deeply-stauiing  cells  (crescents  of  Gianuzzi)  outside  the  columnar  layer 
(Fig.  158,  A",  B"),  and  between  it  and  the  basement  membrane,  while 
the  gland-tubes  of  the  fundus  of  the  stomach  have  in  the  same  situation 
a  discontinuous  layer  of  large  ovoid  cells,  termed  parietal  from  their 
position,  oxyntic  (or  acid-secreting)  from  their  supposed  function 
(Figs.  155-157).  Access  to  the  lumen  of  the  glands  is  provided  for 
these  deeply-placed  parietal  cells  and  for  the  cells  of  the  crescents  by 
fine  branching  channels  which  enter  and  surround  the  cells.  The 
serous  salivary  glands,  the  pyloric  glands  of  the  stomach,  and  the 
Lieberkiihn's  crypts,  have  but  a  single  layer  of  epithelium;  and  since 
there  is  no  hepatic  cell  which  is  not  in  contact  with  at  least  one  bile 
capillary,  the  liver  may  be  regarded  as  having  no  more.  The  same  is 
true  of  the  pancreatic  alveoli,  except  that  in  the  centre  of  many  of  the 
acini  a  few  spindle-shaped  cells  (centre -acinar  cells),  apparently  con- 
tinued from  the  lining  of  the  smallest  ducts,  may  be  seen.  Remarkable 
histological  changes,  evidently  connected  with  changes  in  functional 
activity,  have  been  noticed  in  most  of  the  digestive  glands.  In  dis- 
cussing these,  it  will  be  best  to  omit  for  the  present  any  detailed  reference 
to  the  liver,  since,  although  there  are  histological  marks  of  secretive 
activity  in  this  gland  as  well  as  in  others,  and  of  the  same  general 
character,  they  are  accompanied,  and  to  some  extent  overlaid,  by  the 
microscopic  evidences  of  other  functions  (p.  526).  The  serous  salivary 
glands  and  the  pancreas  can  be  taken  together ;  so  can  the  glands  of  the 
various  regions  of  the  stomach;  the  mucous  salivary  glands  must 
be  considered  separately. 

Changes  in  the  Pancreas  and  Parotid  during  Secretion. — ^The  cells 
of  the  alveoli  of  the  pancreas  or  parotid  during  rest,  as  can  be  seen 
by  examining  thin  lobules  of  the  former  between  the  folds  of  the 
mesentery  in  the  hving  rabbit,  or  fresh  teased  preparations  of  the 
latter,  are  filled  with  fine  granules  to  such  an  extent  as  to  obscure 
the  nucleus.  In  the  parotid  the  whole  cell  is  granular,  in  the 
pancreas  there  is  still  a  narrow  clear  zone  at  the  outer  edge  of  the 
cell  which  contains  few  granules  or  none;  in  both,  the  divisions 
between  the  cells  are  very  indistinct,  and  the  lumen  of  the  alveolus 
cannot  be  m\de  out.  During  activity  the  granules  seem  to  be 
carried  from  the  outer  portion  of  the  cell  towards  the  lumen,  and 

24 


37° 


DIGESTION 


there  discharged.  The  clear  outer  zone  of  the  pancreatic  cell  grows 
broader  and  broader  at  the  expense  of  the  inner  granular  zone,  until 
at  last  the  granular  zone  may  in  its  turn  be  reduced  to  a  narrow 
contour  line  around  the  lumen  (Fig.  153).  In  the  uniformly  clouded 
parotid  cell  a  similar  change  takes  place;  a  transparent  outer  zone 

arises;  and,  after  prolonged 
secretion,  only  a  thin  edging 
of  granules  may  remain  at 
the  inner  portion  of  the  cell 
(Fig.  154).  In  both  glands 
the  outhnes  of  the  cells  be- 
come more  clearly  indicated, 
and  a  distinct  lumen  can 
now  be  recognized.  The 
cells  are  smaller  than  they 
are  during  rest. 

The  disappearance  of 
granules  from  without  in- 
wards during  activity  sug- 
gests that  these  are  manu- 
factured products  eliminated  in  the  secretion,  and  they  are  generally 
spoken  of  as  zymogen  granules. 

Bensley,  who  has  made  a  careful  study  of  the  pancreas  in  the 
guinea-pig,  has  been  able  to  distinguish,  even  in  fresh  preparations 
examined  in  the  animal's  own  serum,  but  better  after  staining  with 
such  a  dye  as  neutral  red,  another  kind  of  granules,  which  he  regards 


Fig.  153. — A,  alveolus  of  rabbit's  pancreas, 
'loaded'  {resting);  B,  'discharged' 
(active),  observed  in  the  living  animal 
(Kiihne  and  Lea). 


Fig.  154. — .\lveoli  of  Parotid  Gland:  A,  at  Rest;  B,  after  a  Short  Period  of  Activity; 
C,  after  a  Prolonged  Period  of  Activity  (Fresh  Preparations)  (Langley).  In  A 
and  B  the  nuclei  are  obscured  by  the  granules  of  zymogen. 

as  zymogen  granules  in  the  course  of  formation,  and  therefore 
designates  prozymogen  granules.  The  resting  acini  show  a  clear 
basal  zone  which  is  unstained,  and  a  zone  next  the  lumen  containing 
coarse  zymogen  granules  which  are  faintly  stained.  In  the  active 
gland — e.g..  after  a  meal  or  after  the  injection  of  secretin  (p.  401) — 
prozymogen  granules  which  stain  much  more  intensely  than  the 
zymogen  granules  with  neutral  red  mike  their  appearance  between 
the  zymogen  granules,  now  much  reduced  in  number  and  size,  and 


THE  SECRETION  OF  THE   DIGESTIVE  JUICES 


371 


f:: 


the  clear  outer  zone.  After  prolonged  secretion  the  zymogen  granules 
may  be  entirely  absent  from  the  cells,  and  only  a  narrow  rim  of 
prozymogen  granules  can  be  seen  around  the  lumen. 

In  one  respect  the  pancreas  differs  remarkably  from  the  salivary 
glands — namely,  in  the  presence  of  the  islets  of  Langerhans — • 
characteristic  groups  of  small 
polygonal  cells,  richly  sup- 
plied with  bloodvessels,  but 
not  arranged  in  the  form  of 
alveoli.  Some  observers  state 
that  they  are  remarkably  in- 
creased in  size,  and  even  in 
number  when  the  pancreas  is 
caused  to  secrete  actively  by 
repeated  injections  of  secretin, 
and  also  in  starvation.  But 
it  has  been  shown  that  this 
conclusion  was  based  upon 
faulty  methods  of  counting 
the  islets,  and  even  of  identi- 
fying the  islet  cells.  There 
appears  to  be  no  foundation 
for  the  view  that  they  are 
derived  from  the  ordinary 
secreting  cells,  and  that  they 
can,  in  turn,  give  rise  to  new 
alveoli  by  a  process  of  pro- 
liferation. It  is  far  more 
probable  that  they  are  inde- 
pendent structures,  with  a 
different  function  from  the 
pancreatic  alveoli  (p.  624). 

Changes  in  the  Glands  of 
the  Stomach  during  Secre- 
tion.— The  mucous  membrane 
of  the  stomach  is  covered 
with  a  single  layer  of  colum- 
nar epithelium,  largely  con- 
sisting of  mucigenous  goblet- 
cells.  It  is  studded  with 
minute  pits,  into  which  open 
the  ducts  of  the  peptic  and  pyloric  glands,  the  ducts  being  lined 
with  cells  just  like  those  of  the  general  gastric  surface.  Three 
varieties  of  gastric  glands  have  been  distinguished:  (i)  The 
glands  of  the  cardia.  In  man  these  occupy  a  small  porticjn  of 
the   mucous   membrane   at  the   cardiac  end,  near  the  orifice  of 


Fig.  156. 

Fig.  155. — A  Fundus  Gland  of  Simple  Form 
from  the  Bat's  Stomach  (Osmic  Acid  Pre- 
paration) (Langley).  c.  Columnar  epithe- 
lium of  the  surface;  n,  neck  of  the  gland 
with  chief  or  central  and  parietal  cells; 
/,  base,  occupied  only  by  chief  cells,  which 
show  the  granules  accumulated  towards 
the  lumen  of  the  gland. 

Fig.  156. — A  Fundus  Gland  prepared  by 
Golgi's  Method,  showing  the  Mode  of  Com- 
munication of  the  Parietal  Cells  with  the 
Gland-Lumen  (Schafer,  after  E.  MuUcr). 


372  DIGESTION 

the  oesophagus.  Some  of  the  glands  are  single  tubules,  but 
others  have  two  or  more  tubules  opening  into  a  common  duct. 
Both  are  lined  by  a  single  layer  of  short  columnar  epithelium, 
which  contains  granules.  (2)  The  glands  of  the  pyloric  canal 
or  antrum.  These  consist  of  short,  branched  tubules,  which  open 
by  twos  and  threes  into  long  ducts.  (3)  The  glands  of  the 
fundus  or  oxyntic  glands,  occupying  the  intermediate  and  greater 
portion  of  the  organ.  The  gland  tubules  are  long  and  seldom 
branched,  and  the  ducts,  into  each  of  which  open  from  one  to  three 
tubules,  are  relatively  short.  The  secreting  parts  of  both  kinds-  of 
glands  are  lined  by  short  columnar  granular  cells;  and  in  the  pyloric 
tubules  no  others  are  present.  But,  as  we  have  said,  in  the  glands 
of  the  fundus  there  are  besides  large  ovoid  cells  scattered  at  intervals 
like  beads  between  the  basement  membrane  and  the  lining  or  chief 
cells.  The  cells  of  the  pyloric  glands  have  a  general  resemblance  to 
the  chief  cells  of  the  fundus  glands,  but  they  are  not  quite  the  same. 
For  example,  the  granules  are  less  distinct  in  the  pyloric  glands.  In 
the  human  stomach  it  is  only  quite  near  the  pylorus  that  the  parietal 
cells  disappear  altogether.  The  parietal  cells  also  contain  granules, 
but  they  are  smaller  and  less  numerous  than  those  of  the  chief  cells, 
so  that  the  deeper  portions  of  the  fundus  glands  are  much  darker  in 
appearance  than  the  more  superficial  portions,  since  the  oxyntic  or 
parietal  cells  are  more  numerous  in  the  neighbourhood  of  the  ducts 
(Bensley). 

The  histological  changes  connected  with  gastric  secretion  do  not 
differ  essentially  from  those  described  in  the  pancreas  and  the 
parotid,  but  there  is  much  greater  difficulty  in  making  observations 
on  the  living,  or  at  least  but  slightly  altered,  cells.  For  the  mammal 
the  best  method  is  to  use  animals  with  a  permanent  gastric  fistula, 
and  to  remove  from  time  to  time  small  portions  of  the  mucous 
membrane  for  examination  in  the  fresh  condition.  During  digestion 
the  granules  disappear  from  the  outer  part  of  the  chief  cells  of  the 
fundus  glands,  leaving  a  clear  zone,  the  lumen  being  bordered  by  a 
granular  layer.  Or,  more  rarely,  there  may  be  a  uniform  decrease 
in  the  number  of  granules  throughout  the  cell.  The  total  volume 
of  the  cell  is  less  than  in  the  fasting  condition.  The  parietal  cells, 
which  are  small  in  the  fasting  animal,  swell  up,  so  as  to  bulge  out  the 
membrana  propria.  They  reach  their  maximum  size  (in  the  dog) 
very  late  in  digestion  (the  thirteenth  to  the  fifteenth  hour).  No 
such  definite  changes  in  their  contents  as  those  observed  in  the  other 
cells  have  been  made  out.  The  granules  in  the  ovoid  cells  during 
and  after  activity  seem  to  be  as  large  and  as  numerous  as  in  the 
resting  cell,  or  even  larger.  After  sham  feeding  in  dogs  the  histo- 
logical changes  in  the  gastric  glands  are  very  slight,  even  when  con- 
siderable amounts  of  gastric  juice  have  been  secreted  (Noll  and 
Sokoloff). 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES 


373 


The  chief  cells  of  the  oxyntic,  and  the  similar  if  not  identical  cells 
of  the  pyloric  glands,  arc  believed  to  manufacture  the  pepsin-form- 
ing substance.  The  ovoid  cells  of  the  former  are  supposed  to  secrete 
the  hydrochloric  acid.  The  evidence  on  which  this  belief  is  based 
is  as  follows: 

The  glands  of  the  antrum  pylori  in  the  dog,  in  which  in  most 
situations  no  ovoid  cells  are  to  be  seen,  secrete  pepsin,  but  no  acid. 
The  pyloric  end  of  the  stomach  or  a  portion  of  it  has  been  isolated, 


-'I 


/'■ 

'.    ■  '-'     ".    > 

'             I  i"        T-    .   ' 

1: 

'    'y    ■/'^■■~- '  ' 

1 

~  -^--^' ' 

'v        -"           ' 

1 1 

Fig    157 — The  Gastric  Clauds  (Ebsteiii).     Oiiili'    In.  1  1  _  hi .  pyi    ;  r. 

the  continuity  of  the  alimentary  canal  restored  by  sutures,  and  the 
secretion  of  the  pyloric  pocket  collected.  It  was  found  to  be  alka- 
hne,  and  contained  pepsin.  The  glands  of  the  frog's  oesophagus, 
which  contain  only  chief  cells,  secrete  pepsin,  but  no  acid.  It  seems 
fair  to  conclude  that  the  chief  cells  of  the  fundus  glands  in  the 
mammal  secrete  none  of  the  free  hydrochloric  acid,  but  certainly 
some  of  pepsin.  But  it  does  not  follow  that  all  the  pepsin  is  formed 
by  these  cells,  although  it  would  scorn  that  all  the  hydrochloric  acid 


374  DIGESTION 

must  be  secreted  by  the  only  other  glandular  elements  present,  the 
parietal  or  '  border  '  cells.  And,  indeed,  the  glands  in  the  fundus 
of  the  frog's  stomach,  which  are  composed  only  of  ovoid  cells,  whilst 
secreting  much  acid,  also  form  some  pepsin,  although  far  less  than 
the  oesophageal  glands.  During  winter  sleep  (in  the  marmot)  the 
production  of  hydrochloric  acid  in  the  parietal  cells  stops  altogether, 
while  the  chief  cells  continue  to  accumulate  granules  of  pepsinogen. 

That  some  pepsin  is  secreted  by  the  pyloric  end  of  the  stomach 
is  not  difficult  to  prove.  The  secretion  collected  from  the  isolated 
pyloric  portion  is,  indeed,  like  the  secretion  of  the  Brunner's  glands 
in  the  duodenum,  quite  unable  to  digest  protein  until  dilute  hydro- 
chloric acid  is  added.  But  this  is  because  in  both  cases  the  juice  as 
it  flows  from  the  glands  is  slightly  alkaline,  and,  as  we  have  already 
seen,  pepsin  only  acts  in  the  presence  of  an  acid.  The  milk-curdling 
action  of  these  two  juices  also  unfolds  itself  only  when  the  secretions 
are  first  acidulated,  and  later  on  again  neutralized;  in  other  words, 
the  ferments  must  be  activated  by  the  addition  of  an  acid.  In  normal 
digestion  the  pepsin  of  the  (in  itself)  alkaline  secretion  of  the  pyloric 
end  of  the  stomach  becomes  a  constituent  of  the  acid  gastric  juice; 
and  it  may  perhaps  be  considered  a  morphological  accident,  so  to 
speak,  that  the  oxyntic  cells  of  the  fundus  should  mingle  their  acid 
products  with  the  (presumedly)  alkaline  secretion  of  the  chief  cells 
in  the  lumen  of  each  gland-tube,  instead  of  being  massed  as  a 
separate  organ  with  a  special  duct. 

We  are  not  without  other  examples  of  digestive  juices  fitted  or 
destined  to  act  in  a  medium  with  an  opposite  reaction  to  their  own. 
The  '  saliva  '  of  the  cephalopod  Octopus  macropus,  strongly  acid 
though  it  is,  contains  a  proteolytic  ferment  which  in  vitro  acts,  like 
trypsin,  better  in  an  alkaline  than  in  an  acid  solution.  And  trypsin, 
whose  precursor  is  a  constituent  of  the  alkaline  pancreatic  juice,  while 
the  enterokinase  which  activates  it  is  a  constituent  of  the  alkaline 
succus  entericus,  performs  a  part  at  least  of  its  work  in  an  acid 
medium. 

Attempts  made  to  demonstrate  an  acid  reaction  in  the  border  cells 
have  hitherto  failed.  Harvey  and  Bensley  on  the  basis  of  experiments 
with  dyes  (cyanimin  and  neutral  red),  which  give  different  colours 
according  to  whether  tlie  reaction  is  acid,  alkaUne,  or  neutral,  have 
concluded  that  free  acid  exists  only  on  the  internal  surface  of  the 
stomach,  or  at  most  also  in  the  necks  of  the  glands.  The  parietal  cells 
they  find  alkaline.  They  suggest  that  these  cells  form  in  some  way, 
of  course  ultimately  from  the  chlorides  of  the  blood,  a  chloride  of  an 
organic  base  which  does  not  decompose  so  as  to  yield  free  hydrochloric 
acid  until  it  reaches  the  mouth  of  the  gland.  The  nature  of  this  decom- 
position, if  it  occurs,  is  unknown.  It  maybe  mentioned,  although  only 
as  a  matter  of  historical  interest,  that  some  observers  have  denied  that 
the  acid  is  secreted  in  the  depths  of  any  cell  from  the  chlorides  of  the 
blood,  and  have  asserted  that  it  is  formed  at  the  surface  of  contact  of 
the  stomach-wall  with  the  gastric  contents  from  the  sodium  chloride  of 
the  food  by  an  exchange  of  sodium  ions  (p.  422)  for  hydrogen  ions  from 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES  375 

the  blood  or  lymph.  It  was  pointed  out  in  favour  of  this  view  that 
when,  instead  of  sodium  chloride,  sodium  bromide  is  given  in  the  food, 
the  hydrochloric  acid  in  the  stomach  is  to  a  large  extent  replaced  by 
hydrobromic  acid.  And  it  was  argued  that  this  cannot  be  due  to  the 
decomposition  of  the  bromide  by  hydrochloric  acid,  since  it  occurs  in 
animals  deprived  for  a  considerable  time  of  salts,  arKi  in  '  salt-hunger  ' 
the  stomach  contains  no  acid  (Koeppe).  It  may  be,  however,  that 
even  in  '  salt-hunger  '  the  presence  of  sodium  bromide  in  the  stomach 
stimulates  the  secretion  of  hydrochloric  acid,  which  then  decomposes 
the  bromide,  with  the  formation  of  hydrobromic  acid.  The  sodium 
chloride  formed  in  the  double  decomposition  might  be  re-absorbed, 
and  the  stock  of  chlorides  in  the  blood  remain  undiminished.  It  is  in 
any  case  a  decisive  objection  to  this  now  defunct  theory  that  a  copious 
secretion  of  gastric  juice,  containing  hydrochloric  acid  in  abundance, 
can  be  obtained,  without  the  introduction  of  any  food  into  the  stomach, 
either  by  the  process  of  sham  feeding  (p.  395)  or  by  psychical  stimulation 
of  the  gastric  glands  when  food  is  shown  to  an  animal. 

Changes  in  Mucous  Glands  during  Secretion. — In  the  mucous  salivary 
and  other  mucous  glands  similar,  but  apparently  more  complex,  changes 
occur.  During  rest  the  cells  which  line  the  lumen  may  be  .seen  in  fresh, 
teased  preparations  to  be  filled  with  granules  or  '  spherules.'  After 
active  secretion  there  is  a  great  diminution  in  the  number  of  the 
granules.  Those  that  remain  are  chiefly  collected  around  the  lumen, 
although  some  may  also  be  seen  in  the  peripheral  portion  of  the  cell; 
and  there  is  no  very  distinct  differentiation  into  two  zones.  That  a 
discharge  of  material  takes  place  from  these  cells  is  shown  by  their 
smaller  size  in  the  active  gland.  That  the  material  thus  discharged  is 
not  protoplasmic  is  indicated  by  the  behaviour  of  the  cells  to  proto- 
plasmic stains  such  as  carmine.  The  resting  cells  around  the  lumen 
stain  but  feebly,  in  contrast  to  the  deep  stain  of  the  demilunes,  while 
the  discharged  cells  take  on  the  carmine  stain  much  more  readily. 
Further,  when  a  resting  gland  is  treated  with  various  reagents  (water, 
dilute  acids,  or  alkalies),  the  granules  swell  up  into  a  transparent  sub- 
stance identical  with  mucin,  which  fills  the  meshes  of  a  fine  protoplasmic 
network. 

In  ordinary  alcohol-carmine  preparations  only  the  network  and 
nucleus  are  stained ;  the  nucleus,  small  and  shrivelled,  is  situated  close 
to  the  outer  border  of  the  cell.  When  a  discharged  gland  is  treated  in 
the  same  way  there  is  proportionally  more  '  protoplasm  '  (or  '  bioplasm  ') 
and  less  of  the  clear  material,  what  remains  of  the  latter  being  chiefly 
in  the  inner  portion  of  the  cell,  while  the  nucleus  is  now  large  and 
spherical,  and  not  so  near  the  basement  membrane  (Fig.  158). 

Ever3d:hing,  therefore,  points  to  the  granules  in  what  we  may  now 
call  the  mucin-forming  cells  as  being  in  some  way  or  other  precursors 
of  the  fully-formed  mucin ;  manufactured  during  '  rest  '  by  the  proto- 
plasm and  partly  at  its  expense,  moved  towards  the  lumen  in 
activity,  discharged  as  mucin  in  the  secretion.  It  has  been  asserted 
that  not  only  is  the  protoplasm  lessened  in  the  loaded  cell  and  re- 
newed after  activity,  but  that  many  of  the  mucigenous  cells  may  be 
altogether  broken  down  and  discharged,  their  place  being  supplied 
by  proliferation  of  the  small  colls  of  the  demilunes.  This  conclusion, 
however,  is  not  supported  by  suificicnt  evidence.  The  cells  of  the 
crescents  contain  fine  granules,  but  none  which  can  be  changed  into 


376 


DIGESTION 


mucin.  They  are  of  serous  and  not  of  mucous  type.  But  the  fact 
on  which  we  would  specially  insist  is  that  the  granules  of  the  resting 
mucigenous  cell  may  be  looked  upon  as  a  mother-substance  from 
which  the  mucin  of  the  secretion  is  derived;  they  are  not  actual,  but 
potential,  mucin. 

So  in  the  pancreas,  the  serous  or  albuminous  sahvary  glands,  and 
the  glands  of  the  stomach,  there  is  every  reason  to  believe  that  the 
granules  which  appear  in  the  intervals  of  rest,  and  are  moved 
towards  the  lumen  and  discharged  during  activity,  are  the  pre- 
cursors, the  mother-substances,  of  important  constituents  of  the 
secretion.  These  granules  are  sharply  marked  off  from  the  proto- 
plasm in  which  they  lie  and  by  which  they  are  built  up.  By  every 
mark,  by  their  reaction  to  stains,  for  instance,  they  are  non-living 
substance,  formed  in  the  bosom  of  the  hving  cell  from  the  raw 
material  which  it  culls  from  the  blood,  or,  what  is  more  hkely, 
formed  from  its  own  protoplasm,  then  shed  out  in  granular  form  and 


Fig.  158. — Mucous  Cells  (from  Submaxillary  of  Dog)  in  Rest  and  Activity  (Langley). 

A,  B,  fresh;  A',  B',  after  treatment  with  dilute  acetic  acid;  A",  B",  alveoli  hard- 
ened in  alcohol  and  stained  with  carmine.     A,  A',  and  A"  represent  the  loaded; 

B,  B',  and  B",  the  discharged  condition. 

secluded  from  further  change.  The  granules  in  the  ferment-forming 
glands  are  not  in  general  composed  of  the  actual  ferments,  and, 
indeed,  in  several  instances  it  has  been  shown  that  the  actual  fer- 
ments are  not  present  in  the  secreting  cells  at  all. 

We  have  already  seen  that  the  pancreas  and  even  the  fresh  pan- 
creatic juice  are  devoid  of  active  trypsin.  Similarly,  a  glycerin- 
extract  of  a  fresh  gastric  mucous  membrane  is  inert  as  regards 
proteins,  or  nearly  so.  But  if  the  mucous  membrane  has  been  pre- 
viously treated  with  dilute  hydrochloric  acid,  the  glycerin  extract 
is  active,  as  is  an  extract  made  with  acidulated  glycerin.  Here  we 
must  assume  the  existence  in  the  gastric  glands  of  a  mother-sub- 
stance, pepsinogen,  from  which  pepsin  is  formed.  The  rennin  of  the 
gastric  juice,  which  is  formed  in  the  chief  cells,  also  has  a  precursor, 
which,  if  the  ferment  is  identical  with  pepsin  (p.  347),  must  be 
pepsinogen.     The  proteolytic  power  of  an  extract  of  the  pancreas, 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES  377 

when  the  trypsinogen  has  been  activated  into  trypsin,  or  of  the 
gastric  mucous  membrane,  when  the  pepsinogen  has  been  changed 
into  pepsin,  seems  to  be,  roughly  speaking,  in  proportion  to  the 
quantity  of  granules  present  in  the  cells.  Therefore  it  is  concluded 
that  the  granules  represent  mother-substances  of  the  ferments  or 
zymogens.  Some  observers  believe  they  have  obtained  evidence  of 
stages  in  the  elaboration  of  the  ferments  still  further  back  than  the 
mother-substances,  grandmother-substances  so  to  speak,  or  pro- 
zymogens.  Bensley,  e.g.,  concludes  that  the  nuclei  of  the  chief  cells 
in  the  fundus  glands  of  the  stomach  take  part  in  the  formation  of  a 
prozymogcn,  the  precursor  of  the  zymogen  or  pepsinogen,  as  pepsino- 
gen is  the  precursor  of  the  enzyme  pepsin. 

A  glycerin  or  watery  extract  of  the  salivary  glands  always  con- 
tains active  amylolytic  ferment,  if  the  natural  secretion  is  active. 
So  that  if  ptyalin  is  preceded  by  a  zymogen  in  the  cells,  it  must  be 
very  easily  changed  into  the  actual  ferment. 

But  wc  should  greatly  deceive  ourselves  if  we  supposed  that  granules 
of  this  nature  in  gland-cells  are  necessarily  related  to  the  production  of 
ferments.  The  mucigenous  granules  have  no  such  significance.  Most 
digestive  secretions  contain  protein  constituents,  with  which  the 
granules  may  have  to  do  as  well  as  with  ferments.  And  bile,  a  secretion 
which  contains  no  mucin,  no  proteins,  and  either  no  ferments  or  mere 
traces,  as  essential  and  original  constituents,  is  formed  in  cells  with 
granules  so  disposed  and  so  affected  by  the  activity  of  the  gland  as  to 
suggest  some  relation  between  them  and  the  process  of  secretion.  In 
the  liver-cells  of  the  frog,  in  addition  to  glycogen,  and  oil-globules  small 
granules  may  be  seen,  especially  near  the  lumen  of  the  gland  tubules; 
they  diminish  in  number  during  digestion,  when  the  secretion  of  bile  is 
active  and  increase  when  food  is  withheld  and  secretion  slow.  And 
in  fasting  dogs  the  secreting  cells  of  Brunncr's  glands,  the  pyloric  glands 
and  the  pancreas,  as  well  as  the  lining  epithelium  of  the  bile-ducts, 
have  been  found  to  contain  many  fatty  granules.  Possibly  some  of 
these  represent  the  fat  which  is  known  to  be  excreted  into  the  alimentary 
canal  (pp.  437,  438). 

The  Nature  of  the  Process  by  which  the  Digestive  Secretions  are 
Formed. — \Vc  have  spoken  more  than  once  of  the  gland-cells  as 
manufacturing  their  secretions.  It  is  an  idea  that  rises  naturally 
in  the  mind  as  we  follow  with  the  microscope  the  traces  of  their 
functional  activity.  And  when  we  compare  the  composition  of  the 
digestive  juices  with  that  of  the  blood-plasma  and  lymph,  the 
suggestion  that  the  glands  which  produce  them  are  not  merely 
passive  filters,  but  living  laboratories,  acquires  additional  strength. 
It  is  evident  that  everything  in  the  secretion  must,  in  some  form 
or  other,  exist  in  the  blood  which  comes  to  the  gland,  and  in  the 
lymph  which  bathes  its  cells.  No  glandular  cell,  if  we  except  the 
leucocytes,  which  in  some  respects  are  to  be  considered  as  unicellular 
glands,  dips  directly  into  the  blood ;  everything  a  gland-cell  receives 
must  pass  through  the  walls  of  the  bloodvessels.     (But  see  footnote 


378  DIGESTION 

on  p.  14).  So  that  anything  which  we  find  in  the  secretion  and  do 
not  find  in  the  blood  must  have  been  elaborated  by  the  gland 
epithelium  (or  by  the  capillary  endotheUum)  from  raw  material 
brought  to  it  by  the  blood. 

Take,  for  example,  the  saliva  or  gastric  juice.  These  liquids  both 
contain  certain  things  that  also  exist  in  the  blood,  but  in  addition 
they  contain  certain  things  specific  to  themselves:  mucin  in  saliva, 
hydrochloric  acid  in  gastric  juice,  ferments  in  both.  It  is  true  that 
a  trace  of  pepsin  and  a  trace  of  a  diastatic  ferment  may  be  dis- 
covered in  blood;  but  there  is  no  reason  whatever  to  beUeve  that 
this  is  the  source  of  the  pepsin  of  the  gastric  juice,  or  the  ptyalin 
of  the  salivary  glands,  except,  perhaps,  in  animals  like  the  cat, 
whose  saliva  contains  a  diastase  in  still  smaller  concentration  than 
the  serum  (Carlson).  On  the  contrary,  it  is  possible  that  the  fer- 
ments of  the  blood  may  be  in  part  absorbed  from  the  digestive 
glands,  the  rest  being  formed  by  the  leucocytes  and  liberated  when 
they  break  down. 

Formation  of  Bile. — The  liver  affords  an  even  better  example  of 
this  '  manufacturing  '  activity  of  gland-cells,  and  many  facts  may 
be  brought  forward  to  prove  that  the  characteristic  constituents 
of  the  bile,  the  bile-pigments  and  bile-acids,  are  formed  in  the  liver, 
and  not  merely  separated  from  the  blood.  Bile-pigment  has  indeed 
been  recognized  in  the  normal  serum  of  the  horse,  and  bile-acids  in- 
the  chyle  of  the  dog,  but  only  in  such  minute  traces  as  are  easily 
accounted  for  by  absorption  from  the  intestine.  Frogs  live  for  some 
time  after  excision  of  the  liver,  but  no  bile-acids  are  found  in  the 
blood  or  tissues.  But  if  the  bile-duct  be  ligatured,  bile-acids  and 
pigments  accumulate  in  the  body,  being  absorbed  by  the  lymphatics 
of  the  liver  (Ludwig  and  FleischI).  If  the  thoracic  duct  and  the 
bile-duct  are  both  hgatured  in  the  dog,  no  bile-acids  or  pigments 
appear  in  the  blood  or  tissues.  Wertheimer  and  Lepage  state  that 
bile  or  bihrubin  injected  into  a  bile-duct  appears  sooner  in  the 
urine  than  in  the  lymph  of  the  thoracic  duct,  and  therefore  conclude 
that  the  bloodvessels  are  the  most  important  channel  of  absorption. 
This  conclusion,  however,  cannot  be  accepted  until  it  is  shown  that 
in  these  experiments  the  injection  did  not  cause  rupture  of  some 
of  the  hepatic  capillaries  and  direct  entrance  of  the  bile-pigment 
into  the  blood.  It  is  not  improbable  that  the  pressure  attained  by 
the  bile  in  the  bile-capillaries  is  a  factor  in  determining  the  path 
by  which  it  is  absorbed,  and  that  when  the  pressure  rises  beyond 
a  certain  limit  it  may  pass  both  into  the  bloodvessels  and  into  the 
lymphatics.  In  mammals  life  cannot  be  maintained  for  any  length 
of  time  after  Hgature  of  the  portal  vein,  since  this  throws  the  whole 
intestinal  tract  out  of  gear.  But  after  an  artificial  communication 
has  been  made  between  the  portal  and  the  left  renal  vein  or  the 
inferior  cava,  the  portal  maybe  tied  and  the  animal  live  for  months 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES  379 

(Eck).  The  liver  can  now  be  completely  removed,  but  death 
follows  in  a  few  hours.  A  good  method  of  establishing-an  Eck's 
fistula  is  to  make  a  longitudinal  incision  in  the  inferior  vena  cava 
and  the  portal  or  superior  mesenteric  vein,  and  to  suture  the  edges 
of  the  two  openings  together  with  a  very  fine  sewing-needle  and 
thread  (Carrel  and  Guthrie).  In  birds  there  exists  a  communicating 
branch  between  the  portal  vein  and  a  vein  (the  renal-portal)  which 
passes  from  the  posterior  portion  of  the  body  to  the  kidney,  and 
there  breaks  up  into  capillaries;  and  not  only  may  the  portal  be 
tied,  but  the  liver  may  be  completely  destroyed  without  immedi- 
ately killing  the  animal.  In  the  hours  of  life  that  still  remain  to  it 
no  accumulation  of  biliary  substances  (acids  or  pigments)  takes 
place  in  the  blood  or  tissues.  A  further  indication  that  bile-pig- 
ment is  produced  in  the  liver  is  the  fact  that  the  hver  contains 
iron  in  relative  abundance  in  its  cells  (p.  21),  and  ehminates  small 
quantities  of  iron  in  its  secretion.  Now,  bile-pigment,  which  con- 
tains no  iron,  is  certainly  formed  from  blood-pigment,  which  is  rich 
in  iron.  For  haematin,  when  injected  under  the  skin,  has  been  found 
to  appear  almost  quantitatively  in  the  form  of  bile-pigment  in  the 
bile,  and  haematoidin  (Fig.  159),  a  crystalhne 
derivative  of  haemoglobin  found  in  old  ex- 
travasations of  blood,  especially  in  the  brain 
and  in  the  corpus  luteum,  is  identical  with 
bilirubin.  The  fact  that  one  of  the  derivatives 
of  hoematin,  haematoporphyrin  (C33H38N4O6), 
contains    no    iron,    and   is    probably   nearly 

related   to    bilirubin    (C32H36N4O6),    suggests  

that  haematoporphyrin  may  be  an  inter-  ^.^  ijg.-Hsmatoidin. 
mediate  step  in  the  formation  of  bile-pigment 

from  blood-pigment.  In  any  case,  the  seat  of  formation  of  bile- 
pigment  might  be  expected  to  be  an  organ  peculiarly  rich  in  iron. 
The  existence  of  haematoidin,  however,  shows  that  bile-pigment 
may,  under  certain  conditions,  be  formed  outside  of  the  hepatic 
cells.  The  occurrence  of  bihverdin  in  the  placenta  of  the  bitch 
points  in  the  same  direction.  But  the  pathological  evidence  in 
favour  of  the  pre-formatibn  of  the  biliary  constituents  tends  rather 
to  shrink  than  to  increase.  For  many  cases  of  what  used  to  be 
considered  '  idiopathic  '  or  '  hsematogenic  '  jaundice,  i.e.,  an  accumu- 
lation of  bile-pigments  and  bile-acids  in  the  tissues,  due  to  defective 
elimination  by  the  Hver,  are  now  known  to  be  caused  by  obstruction 
of  the  bile-ducts  and  consequent  re-absorption  of  bile  ('  obstructive  ' 
or  '  hepatogenic  '  jaundice). 

But  if  substances  such  as  the  ferments,  mucin,  hydrochloric  acid, 
the  bile-salts  and  bile-pigments,  are  undoubtedly  manufactured  in  the 
gland-cells,  it  is  different  with  the  water  and  inorganic  salts  which 
form  so  large  a  part  of  every  secretion.     No  tissue  lacks  them;  no 


38o 


DIGESTION 


physiological  process  goes  on  without  them ;  they  are  not  high  and 
special  products.  As  we  breathe  nitrogen  which  we  do  not  need 
because  it  is  mixed  with  the  oxygen  we  require,  the  secreting  cell 
passes  through  its  substance  water  and  salts  as  a  sort  of  by-play  or 
adjunct  to  its  specific  work.  But  this  is  not  the  whole  truth.  The 
gland-cell  is  not  a  mere  filter  through  which  water  and  salts  pass  in 
the  same  proportions  in  which  they  exist  in  the  liquids  that  the 
cell  draws  them  from.  When,  e.g.,  the  salivary  glands  secrete 
against  the  resistance  of  an  abnormally  high  pressure  in  the  ducts, 
the  percentage  of  salts  in  the  saliva  increases.  The  secretions  of 
different  glands  differ  in  the  nature,  and  especially  in  the  relative 
proportions,  of  their  inorganic  constituents.  They  differ  also  in 
their  osmotic  pressure  and  electrical  conductivity,  which  depend 
so  largely  upon  those  constituents,  notwithstanding  the  fact  that 
the  osmotic  pressure  and  conductivity  of  the  blood-serum  (p.  26) 
vary  only  within  narrow  limits.  Even  the  secretion  of  one  and  the 
same  gland  is  by  no  means  constant  in  this  respect,  as  we  shall 
have  to  note  more  especially  when  we  come  to  deal  with  the  in- 
fluence of  the  nervous  system  on  secretion  (p.  389).  The  following 
tables  illustrate  this  point: 


Dog. 

Blood-Serum.* 

Filtrate  of  Gastric  Contents. 

At                      KJ(5°C.)x.o*. 

1 

A 

Kt(5°C.)xio''. 

I.                    0-643° 

II.                     0-628° 

III.                     0-602° 

92-0 
87-6 

0-585° 

0-585° 
0-642° 

312-5 
179-4 
351-7 

Vomit  of  man  with  complete   intes- 
tinal obstruction     -             -             - 

o-433° 

847 

Pancreatic  Juice  of  Dog  {Pincussohn). 


Diet. 

A 

Milk            ...               - 
Cauliflower             ... 
Horseflesh               .              _              . 

o-57°-o-63* 
0-58"— 0-63° 
0-62°— 0-63° 

*  The  blood  and  gastric  contents  were  obtained  from  the  animals  in  the 
writer's  laboratory  twenty-four  hours  after  the  last  meal. 

•f  The  depression  of  the  freezing-point  below  that  of  distilled  water, 
t  See  footnote  on  p.  27. 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES 


381 


Gastric  Juice  from  Miniature  Stomach  in  a  Dog  in  Different 
Experiments   [Bickel). 


Milk  Diet. 

Meat  Diet. 

A 

K  (2500x10*. 

A 

K(2S"C.)xio*. 

0-52° 
0-65° 
0-64° 
0-69° 
0-81° 

195-9 
402-6 

436-5 
404-2 

436-5 

o-6o° 

0-71° 
1-21° 

0-79° 
0-70° 

3IO-3 
473-5 
483-3 
514-1 
514-1 

A  of  Blood  and  Saliva  Compared  [Jappelli). 


A  of  Blood. 

A  of  Submaxillary  Saliva  of  Dog. 

0-570° 
0-610° 
0-600° 

0-410° 
0-350° 
0-430° 

0-590° 
0-580° 
0-605° 
0-650° 

0-410° 
0-450° 
0-425° 
0-380° 

0-610° 

0-475° 

A  of  Human  Fistula  Bile. 

A  of  Human  Bladder  Bile. 

0-56° 

0-547° 
0-615° 
0-60° 
0-545° 

0-65° 

0-865" 
0-78° 

0'92° 

A  of  Dog's  Submaxillary  Saliva. 


Chorda  stimulated : 

Left   submaxillary 
Both    glands 

Spontaneous  secretion : 
Right  submaxillary 
A  of  dog's  scrum 


-  0-293" 

-  0-408'= 

-  0-I95" 

-  0-590° 


The  proti'in  substances,  such  as  seruni-albuniin  and  globulin, 
common  to  blood  and  to  some  of  the  digestive  secretions,  take  a 
middle  place  between  the  constituents  that  are  undoubtedly  manu- 


382  DIGESTION 

factured  in  the  cell  and  those  which  seem  by  a  less  special  and 
laborious,  though  a  selective,  process  to  be  passed  through  it  from 
the  blood.  Their  practical  absence  from  bile,  and,  as  we  shall  see, 
from  urine,  their  relative  abundance  in  pancreatic  and  scantiness 
in  gastric  juice,  point  to  a  closer  dependence  upon  the  special 
activity  of  the  gland-cell  than  we  can  suppose  necessary  in  the  case 
of  the  salts. 

Although  it  is  in  the  cells  of  the  digestive  glands  that  the  power  of 
forming  ferments  is  most  conspicuous,  it  is  by  no  means  confined  to 
them.  It  seems  to  be  a  primitive,  a  native  power  of  protoplasm. 
Lowly  animals,  like  the  amoeba,  lowly  plants,  like  bacteria,  form  ferments 
within  the  single  cell  which  serves  for  all  the  purposes  of  their  life. 
The  ferment-secreting  gland-cells  of  higher  forms  are  perhaps  only  lop- 
sided amoebae,  not  so  much  endowed  with  new  properties  as  dispro- 
portionately developed  in  one  direction.  The  contractility  has  been 
lost  or  lessened,  the  digestive  power  has  been  retained  or  increased; 
just  as  in  muscle  the  power  of  contraction  has  been  developed,  and 
that  of  digestion  has  fallen  behind.  The  muscle-cell  and  the  cartilage- 
cell  are  parasites,  if  we  look  to  the  function  of  digestion  alone.  They 
live  on  food  already  more  or  less  prepared  by  the  labours  of  other  cells ; 
and  it  is  a  universal  law  that  in  the  measure  in  which  a  power  becomes 
useless  it  disappears.  But  the  presence  of  pepsin  in  the  white  blood- 
corpuscles,  the  parasites  as  well  as  the  scavengers  of  the  blood,  and  of 
amylolyti^,  proteolytic  and  lipolytic  ferments  in  many  tissues,  should 
warn  us  not  to  conclude  that  the  power  of  forming  ferments  belongs 
exclusively  to  any  class  of  cells.  There  is  good  and  growing  evidence 
that  food-substances  absorbed  from  the  blood  are  further  decomposed 
and,  in  turn,  elaborated  by  ferment  action  within  the  tissues  them- 
selves; while  many  facts  show  that  the  power  of  contraction  is  widely 
diffused  among  structures  whose  special  function  is  very  different, 
and  a  few  point  to  its  possession  in  some  degree  even  by  glandular 
epithelium.  On  the  other  hand,  it  must  be  remembered  that  none  of 
the  digestive  glands  absorb  food  directly  from  the  alimentary  canal  to 
be  then  digested  within  their  own  cell-substance ;  the  ferments  which 
they  form  do  their  work  outside  of  them ;  their  cells  feed  also  upon  the 
blood. 

Why  are  the  Tissues  of  Digestion  not  affected  by  the  Digestive 
Ferments  ? — This  is  the  place  to  mention  a  point  which  has  been 
very  much  debated.  Why  is  it  that  the  stomach  or  the  small  intes- 
tine does  not  digest  itself  ?  This  is  really  a  part  of  a  wider  question  : 
Why  is  it  that  living  tissues  resist  all  kinds  of  influences,  which  attack 
dead  tissues  with  success  ?  And  we  have  to  inquire  whether  the 
immunity  of  the  alimentary  canal  to  the  digestive  juices  is  an 
example  of  a  general  resistance  of  all  living  tissues  to  destructive 
agencies,  or  a  specific  resistance  of  certain  tissues  to  certain  in- 
fluences. 

That  all  living  tissues  cannot  withstand  the  action  of  the  gastric 
juice  has  been  shown  by  putting  the  leg  of  a  living  frog  inside  the 
stomach  of  a  dog;  the  leg  is  gradually  eaten  away  (Bernard). 

It  is  true  that  it  has  first  been  killed  and  then  digested,  but  the 
question   is,   why  the  stomach-wall  is  not   first   killed   and  then 


THE  SECRETION  OF  THE  DIGESTIVE  JUICES  383 

digested  ?  When  the  wall  has  been  injured  by  caustics  or  by  an 
embolus,  the  gastric  juice  acts  on  it.  But  the  Hving  epithelium 
that  covers  it  is  able  to  resist  the  action  of  the  acid  and  pepsin, 
which  destroys  the  tissues  of  the  frog's  leg.  The  explanation  is  not 
to  be  found  in  the  alkalinity  of  the  blood,  for  the  frog's  blood  is  also 
alkaline,  and  the  cells  that  line  the  intestine  are  preserved  from  the 
pancreatic  juice,  which  is  intensely  active  in  an  alkahne  medium, 
while  the  living  frog's  leg  is  not  harmed  by  a  weakly  alkaline  pan- 
creatic extract,  which  does  not  digest  the  epithelium  because  it 
cannot  kill  it.  A  certain  amount  of  protection  may  be  afforded  to 
the  walls  of  the  stomach  by  the  thin  layer  of  mucus  which  covers  the 
whole  cavity,  for  mucin  is  not  affected  by  peptic  digestion.  And 
a  mucous  secretion  seems  in  some  other  cases  to  act  as  a  protective 
covering  to  the  walls  of  hollow  viscera,  whose  contents  are  such  as 
would  certainly  be  harmful  to  more  delicate  membranes,  e.g.,  in 
the  urinary  bladder,  large  intestine,  and  gall-bladder.  Still,  how- 
ever important  such  a  mechanical  protection  may  be,  it  does  not 
explain  the  whole  matter,  and  it  is  necessary  to  suppose  that  the 
gastric  epithelium  has  some  special  power  of  resisting  the  gastric 
juice,  either  by  turning  any  of  the  ferment  which'  may  invade  it 
into  an  inert  substance  and  neutralizing  any  intrusive  acid,  or  by 
opposing  their  entrance  as  the  epithelium  of  the  bladder  opposes  the 
absorption  of  urea.  There  is  reason  to  believe  that,  as  a  matter  of 
fact,  free  hydrochloric  acid  cannot  penetrate  the  living  cells,  and 
it  is  to  be  noted  that  both  active  pepsin  and  free  acid  must  be 
present  at  the  same  point  within  the  cells  before  digestion  of  them 
can  take  place.  In  the  gland-cells  of  the  pancreas  the  protoplasm 
is,  no  doubt,  shielded  from  digestion  by  the  existence  of  the  ferment 
in  an  inert  form  as  zymogen ;  and  it  is  possible  that  this  is  one  of  the 
reasons  for  the  existence  of  the  mother-substance.  But  no  such 
explanation  is,  of  course,  available  for  the  intestinal  epithehum. 
Trypsin  when  injected  below  the  skin  causes  the  tissue  to  break 
down  and  ulcerate.  And  while  an  active  solution  of  trypsin  can 
be  allowed  to  remain  a  long  time  in  an  isolated  loop  of  small  intes- 
tine without  producing  any  ill  effect,  damage  is  soon  caused  not 
only  to  the  intestinal  wall,  but  also  to  the  hver,  when  the  mucous 
membrane  of  the  loop  has  been  injured  before  the  introduction  of 
the  trypsin.  We  must  suppose,  then,  that  the  normal  mucous 
membrane  of  the  intestine  prevents  the  absorption  of  trypsin,  or, 
if  it  absorbs  any  of  it,  renders  it  harmless.  On  the  other  hand,  the 
intestinal  mucosa  is  injured  by  the  natural  gastric  juice  when  intro- 
duced directly  into  it  unless  the  animal  takes  food  simultaneously 
or  a  little  earlier.  But  for  reasons  already  given  (p.  364)  injury  to 
the  intestine  cannot  be  produced  in  this  way  in  normal  digestion. 
It  is  impossible  to  escape  the  conclusion  that  each  membrane  becomes 
accustomed,  and,  so  to  speak,  '  immune,'  to  the  secretion  normally 


384  DIGESTION 

in  contact  with  it,   although  not   necessarily  to  other  secretions. 
It  is  easy  to  multiply  illustrations  of  this  principle. 

The  mucosa  of  the  dog's  urinary  bladder  is  digested  by  the 
natural  activated  pancreatic  juice  of  the  dog,  and  still  more  readily 
by  the  natural  gastric  juice.  Yet  few  tissues  but  the  lining  of  the 
urinary  tract  or  of  the  large  intestine  could  bear  the  constant  contact 
of  urine  or  faeces.  When  urine  is  extravasated  under  the  skin,  or 
the  contents  of  the  alimentary  canal  burst  into  the  peritoneal 
cavity,  they  come  into  contact  with  tissues  which,  although  alive, 
are  much  less  fitted  to  resist  them  than  the  surfaces  by  which  they 
are  normally  enclosed;  and  the  consequences,  which  are  not  wholly 
due  to  infection,  are  often  disastrous.  Leucoc5^es  thrive  in 
the  blood,  but  perish  in  urine.  Blood  does  not  harm  the  endo- 
thelial cells  of  the  vessels,  but  kills  a  muscle  whose  cross-section 
is  dipped  into  it.  The  defensive  or,  in  some  cases,  offensive 
liquids  secreted  by  many  animals  are  harmless  to  the  tissues 
which  produce  and  enclose  them.  A  caterpillar  investigated 
by  Poulton  secretes  a  liquid  so  rich  in  formic  acid  that  the  mere 
contact  of  it  would  kill  most  cells.  The  so-called  saliva  of  Octopus 
macropus  contains  a  substance  fatal  to  the  crabs  and  other  animals 
on  which  it  preys.  The  blood  of  the  viper  contains  an  active 
principle  similar  to  that  secreted  by  its  poison-glands,  but  its  tissues 
are  not  affected  by  this  substance,  so  deadly  to  other  animals. 

A  step  in  the  solution  of  our  problem  has  been  taken  by  Wein- 
land.  Starting  with  the  idea  that  if  special  protective  mechan- 
isms against  the  digestive  juices  were  anywhere  to  be  found,  it  would 
be  in  the  intestinal  parasites  whose  whole  existence  is  passed  among 
them,  he  has  made  the  important  discovery  that  in  these  parasitic 
worms  specific  antiferments  exist — i.e.,  substances  which  inhibit  the 
action  either  of  pepsin  or  of  trypsin  or  of  both.  These  substances  can 
be  precipitated  from  the  expressed  juice  of  the  worms  by  alcohol, 
without  completely  losing  their  activity.  Fibrin  can  be  impreg- 
nated with  them,  and  it  is  then,  just  like  the  '  hving  tissue,'  rendered 
for  a  longer  or  shorter  time  unassailable  by  the  proteolytic  ferments. 
These  facts  are  full  of  suggestion  for  future  work,  although  the  sup- 
posed proof  that  similar  antiferments  are  contained  in  the  cells  of 
the  mucous  membrane  of  the  stomach  and  intestines  of  the  higher 
animals  appears  to  have  broken  down.  Substances  can  indeed  be 
obtained  by  Weinland's  method  from  the  gastric  and  intestinal 
mucosa  which,  when  added  to  a  digestive  mixture,  strongly  inhibit 
the  digestion  of  proteins.  But  there  is  no  clear  proof  that  these  sub- 
stances are  specific  antiferments.  They  are  probably  merely  some 
of  the  split  products  of  protein  (Langenskjold).  There  is,  however, 
some  evidence  of  the  existence  of  an  antipepsin  in  many  tissues 
including  the  mucous  membrane  of  the  stomach.  As  already  men- 
tioned, it  is  known  that  an  antitrypsin  exists  in  the  blood,  with  the 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS    385 

same  properties  as  the  antitrypsin  in  the  intestinal  worms  (Haniill). 
This  explains  the  resistance  of  blood-serum  to  the  digestive  action 
of  trypsin.  In  addition  to  this  body,  which  hinders  the  action  of 
fully-formed  trypsin,  and  has  no  effect  upon  enterokinase,  the 
serum  of  some  animals  contains  an  antikinase — i.e.,  a  substance 
which  hinders  the  action,  not  of  trypsin,  but  of  enterokinase,  pre- 
venting it  from  activating  the  trypsinogen  into  trypsin. 


Section  V. — The  Influence  of  the  Nervous  System 
ON  THE  Digestive  Glands. 

The  Influence  of  Nerves  on  the  Salivary  Glands. — All  the  salivary 
glands  have  a  double  nerve-supply,  from  the  medulla  oblongata 
through  some  of  the  cranial  nerves,  and  from  the  spinal  cord  through 
the  cervical  sympathetic  (Fig.  160). 

In  the  dog  the  chorda  tympani  branch  of  the  facial  nerve  carries  the 
cranial  supply  of  the  sublingual  and  submaxillary  glands.  It  joins  the 
lingual  branch  of  the  fifth  nerve,  runs  in  company  with  it  for  a  little 
way,  and  then,  breaking  off,  after  giving  some  fibres  to  the  lingual, 
passes,  as  the  chorda  tympani  proper,  along  Wharton's  duct  to  the 
submaxillary^  gland.  In  the  hilus  of  this  gland  most  of  its  fibres  break 
up  into  fibrils  around  nerve-cells  situated  there,  and  lose  their  medulla 
in  doing  so.  A  few  fibres  terminate  in  a  similar  manner  before  entering 
the  hilus,  and  a  few  deeper  in  the  gland.  The  nervous  path  is  continued 
by  the  axis-cylinder  processes  (p.  824)  of  these  nerve-cells,  which, 
passing  in  as  non-medullatcd  fibres,  end  in  a  plexus  on  the  basement 
membrane  of  the  alveoli.  From  the  plexus  fibrils  run  in  among  the 
gland-cells,  but  do  not  seem  to  penetrate  them.  The  lingual,  the 
chorda  tympani  proper,  and  Wharton's  duct  form  the  sides  of  what  is 
called  the  chordo-lingual  triangle.  Within  this  triangle  are  situated 
many  ganglion  cells,  a  special  accumulation  of  which  has  received  the 
name  of  the  submaxillary  ganglion.  This,  however,  should  rather  be 
called  the  sublingual  ganglion,  since  its  cells,  as  well  as  the  others  in  the 
chordo-lingual  triangle,  are  the  cells  of  origin  of  axons  which  proceed 
as  non-mcdullated  fibres  to  the  sublingual  gland.  The  sublingual  gland 
receives  its  cerebral  fibres  partly  from  branches  given  off  from  the 
lingual  in  the  chordo-lingual  triangle  after  the  chorda  tympani  proper 
has  separated  from  it,  and  ending  around  the  nerve-cells  within  that 
triangle,  partly  from  the  chorda  itself  in  the  terminal  portion  of  its 
course.  These  statements  rest  on  anatomical  and  physiological  evi- 
dence.    The  latter  we  shall  return  to. 

The  cerebral  fibres  for  the  parotid  (in  the  dog)  pass  from  the  tympanic 
branch  of  the  glosso-pharyngcal  (Jacobson's  nerve)  through  connecting 
filaments  to  the  small  superficial  petrosal  branch  of  the  facial,  witli 
this  nerve  to  the  otic  ganglion,  and  thence  by  the  auriculo-temporal 
branch  of  the  fifth  to  the  gland. 

The  sympathetic  fibres  for  all  the  salivary  glands  appear  to  arise  from 
nervc-cclls  in  the  upper  dorsal  portion  of  the  spinal  cord.  Issuing 
from  the  cord  in  the  anterior  roots  of  the  upper  thoracic  nerves  (first  to 
fifth,  but  mainly  second  thoracic  for  the  submaxillary),  they  enter  the 
sympathetic  chain,  in  which  they  run  up  to  the  superior  cervical 
ganglion.     Here  they  break  up  into  terminal  twigs,  and  thus  come  into 

25 


386 


DIGESTION 


relation  with  ganglion  cells,  whose  axons  pass  out  as  non-medullated 
fibres,  and,  surrounding  the  external  carotid,  reach  the  salivary  glands 
along  its  branches.  Langley  has  shown,  by  means  of  nicotine  (p.  i8o), 
that  the  sympathetic  fibres  for  the  submaxillary  and  sublingual,  and, 
indeed,  for  the  head  in  general  in  the  dog  and  cat,  are  connected  with 
nerve-cells  in  this  ganglion,  but  not  between  it  and  their  termination, 
or  between  it  and  their  origin  from  the  spinal  cord. 

Stimulation  of  the 
Cranial  Fibres. — When 
in  a  dog  a  cannula  is 
placed  in  Wharton's 
duct,  and  the  saliva 
collected  (p.  450),  it  is 
found  that  stimulation 
of  the  peripheral  end 
of  the  divided  chorda 
causes  a  brisk  flow  of 
watery  saliva,  and  at 
the  same  time  a  dila- 
tation of  the  vessels 
of  the  gland,  which  we 
have  already  described 
in  dealing  with  vaso- 
motor nerves  (p.  177). 
Notwithstanding  the 
vaso  -  dilatation,  the 
volume  of  the  gland 
is  in  general  dimin- 
ished, owing  to  the 
rapid  passage  of  water 
into  the  duct  (Bunch). 
The  blood  has  been 
shown  to  lose  water  in 
making  the  circuit  of 
the  submaxillary 
gland  during  excita- 
tion of  the  chorda, 
but  doubtless  some 
of  the  water  of  the 
saliva  comes  directly 


Fig.  100  — Nerves  of  the  Salivary  Glands.  SM  and  SL. 
submaxillary  and  sublingual  glands;  P,  parotid; 
V,  fifth  nerve;  VII,  facial;  GP,  glosso-pharyngeal; 
L,  lingual;  CT,  chorda  tympani;  CL,  chordo-lingual; 
D.  submaxillary  (Wharton's)  duct;  C,  ganglion  cell 
of  so-called  submaxillary  ganglion  in  the  chordo- 
lingual  triangle,  connected  with  a  neive  fibre  going 
to  sublingual  gland;  C",  ganglion  cell  in  hilus  of  sub- 
maxillary gland;  SSP,  small  superficial  petrosal 
'branch  of  the  facial;  OG,  otic  ganglion;  IM,  inferior 
maxillary  division  of  fifth  nerve:  AT,  auriculo- 
temporal branch  of  fifth;  JN,  Jacobson's  nerve; 
C,  ganglion  cells  in  superior  cervical  ganglion  (SG) 
connected  with  sympathetic  fibres  going  to  parotid, 
submaxillary  and  sublingual  glands.  The  figure  is 
schematic. 


from  the  cells  or  from 
the  lymph.  That  the  increased  secretion  is  not  due  merely  to  the 
greater  blood- supply,  and  the  consequent  increase  of  capillary  pres- 
sure, is  shown  by  the  injection  of  atropine,  after  which  stimulation 
of  the  nerve,  although  it  still  causes  dilatation  of  the  vessels,  is  not 
followed  by  a  flow  of  saliva.  Mere  increase  of  pressure  could  not 
in  anv  case  of  itself  account  for  the   secretion,  since  it  has  been 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     387 

found  that  the  maximum  pressure  in  the  saHvary  duct  when  the 
outflow  of  saHva  from  the  duct  is  prevented  may,  during  stimula- 
tion of  the  chorda,  much  exceed  the  arterial  blood-pressure  (Ludwig). 
In  one  experiment,  for  example,  the  pressure  in  the  carotid  of  a  dog 
was  125  mm.,  in  Wharton's  duct  195  mm.  of  mercury. 

Even  in  the  head  of  a  decapitated  animal  a  certain  amount  of 
saUva  may  be  caused  to  flow  by  stimulation  of  the  chorda,  but  too 
much  may  easily  be  made  of  this.  And  since  the  blood  is  the  ultimate 
source  of  the  secretion,  we  could  not  expect  a  permanent  or  copious 
flow  in  the  absence  of  the  circulation,  even  if  the  gland-cells  could 
continue  to  live.  In  fact,  when  the  circulation  is  almost  stopped  by 
strong  stimulation  of  the  sympathetic,  the  flow  of  saHva  caused  by 
excitation  of  the  chorda  is  at  the  same  time  greatly  lessened  or 
arrested,  even  though  the  sympathetic  itself  possesses  secretory 
fibres.  So  that,  while  there  is  no  doubt  that  the  chorda  tympani 
contains  fibres  whose  function  is  to  increase  the  activity  of  the 
gland-cells,  its  vaso-dilator  action  is,  under  normal  conditions, 
closely  connected  with,  and,  indeed,  auxihary  to,  its  secretory  action, 
although  the  dilation  of  the  vessels  does  not  directly  produce  the 
secretion.  This  is  only  a  particular  case  of  a  physiological  law  of 
wide  application,  that  an  organ  in  action  in  general  receives  more 
blood  than  the  same  organ  in  repose,  or,  in  other  words,  that  the 
tissues  are  fed  according  to  their  needs.  The  contracting  muscle,  the 
secreting  gland,  is  flushed  with  blood,  not  because  an  increased  blood- 
flow  can  of  itself  cause  contraction  or  secretion,  but  because  these 
high  efforts  require  for  their  continuance  a  rich  supply  of  what  blood 
brings  to  an  organ,  and  a  ready  removal  of  what  it  takes  away. 

The  quantity  of  blood  passing  through  the  parotid  of  a  horse 
when  it  is  actively  secreting  during  mastication  may  be  quadrupled 
(Chauveau).  The  parallel  between  the  muscle  and  the  gland  is 
drawn  closer  when  it  is  stated  that  electrical  changes  accompany 
secretion  (p.  810),  and  that  the  rate  of  production  of  carbon  dioxide 
and  consumption  of  oxygen  (in  the  submaxillary  gland)  is  three  or 
four  times  greater  during  activity  than  during  rest.  The  temperature 
of  the  saliva  flowing  from  the  dog's  submaxillary  during  stimulation 
of  the  chorda  has  been  found  to  be  as  much  as  15°  C  above  that 
of  the  blood  of  the  carotid,  although  with  the  gland  at  rest  no  con- 
stant difference  could  be  detected  between  the  arterial  blood  and 
the  interior  of  Wharton's  duct.  But  such  measurements  are  open 
to  many  fallacies;  and  while  there  is  no  doubt  that  more  heat  is 
produced  in  the  active  than  in  the  ]>assive  gland,  it  will  not  be 
surprising,  when  the  vastly-increased  blood-flow  is  remembered, 
that  no  difference  of  temperature  between  the  incoming  and  out- 
going blood  has  been  satisfactorily  demonstrated. 

It  has  already  been  mentioned  that  most  of  the  fibres  of  tlic  chorda 
tympani  proper  become  connected  with  ganglion-cells,  and  lose  their 


388  DIGESTION 

medulla  inside  the  submaxillary  gland,  only  a  fe.v  having  already  lost 
it  by  a  similar  connection  with  ganglion-cells  in  the  chordo-lingual 
triangle.  These  facts  have  been  made  out  by  means  of  the  nicotine 
method  previously  described  (p.  i8o).  Thus,  it  is  found  that,  after 
the  injection  of  nicotine  (5  to  10  mg.  in  a  rabbit  or  cat,  40  or  50  mg.  in 
a  dog),  stimulation  of  the  chorda  tympani  proper  or  of  the  chordo- 
lingual  nerve  causes  no  secretion  from  the  submaxillary  gland;  but 
stimulation  of  the  hilus  of  the  gland  is  followed  by  a  copious  secretion — 
as  much,  if  the  stimulation  is  fairly  strong,  as  was  caused  by  excitation 
of  the  nerve  before  injection  of  nicotine.  That  this  is  due  neither  to 
any  direct  action  on  the  gland-cells,  nor  to  stimulation  of  the  sympa- 
thetic plexus  on  the  submaxillary  artery,  but  to  stimulation  of  chorda 
fibres  beyond  the  hilus,  is  shown  by  the  fact  that  after  atropine  has 
been  injected  in  sufficient  amount  to  paralyze  the  nerve  endings  of  the 
chorda,  but  not  of  the  sympathetic,  stimulation  of  the  hilus  causes  little 
or  no  flow  of  saliva.  The  application  of  nicotine  solution  to  the  chordo- 
lingual  triangle  does  not  affect  the  submaxillary  secretion  caused  by 
stimulation  of  the  chordo-lingual  nerve,  even  in  cases  where  a  few 
secretory  fibres  for  the  submaxillary  do  not  leave  the  chordo-lingual 
nerve  in  the  chorda  tympani  proper,  but  are  given  off  to  the  chordo- 
lingual  triangle.  This  shows  that  none  of  the  ganglion-cells  in  the 
triangle  are  connected  with  the  secretory  fibres  of  the  submaxillary 
gland.  By  observations  of  the  same  kind  they  are  known  to  be  con- 
necter! with  fibres  going  to  the  sublingual.  In  a  similar  way,  by  observ- 
ing the  effects  of  stimulation  of  the  chorda  on  the  bloodvessels  before 
and  after  the  application  of  nicotine,  it  has  been  found  that  the  vaso- 
dilator fibres  are  connected  with  ganglion-cells  in  the  same  positions  as 
the  secretory  fibres  (Langley). 

Stimulation  of  the  Sympathetic  Fibres. — The  sympathetic,  as  has 
been  already  indicated,  contains  both  vaso-constrictor  and  secretory 
fibres  for  the  salivary  glands.  If  the  cervical  sympathetic  in  the 
dog  is  divided,  and  the  cephalic  end  moderately  stimulated,  a  few 
drops  of  a  thick,  viscid  and  scanty  saliva  flow  from  the  submaxillary 
and  sublingual  ducts,  while  the  current  of  blood  through  the  glands 
is  diminished.  As  a  rule,  no  visible  secretion  escapes  from  the 
parotid,  but  microscopic  examination  shows  that  many  of  the 
ductules  are  filled  with  fluid,  which  is  apparently  so  thick  as  to  plug 
them  up  (Langley) ;  while  the  cells  show  signs  of  '  activity  '  (p.  370). 

Simultaneous  Stimulation  of  Cranial  and  Sympathetic  Fibres. — 
When  the  chorda  and  sympathetic  are  stimulated  together,  the 
former  prevails  so  far,  with  moderate  stimulation  of  the  latter,  that 
the  submaxillary  saliva  is  secreted  in  considerable  quantity,  and  is 
not  particularly  viscid.  It  is,  however,  richer  in  organic  matter 
than  is  the  chorda  saliva  itself.  When  the  chorda  is  weakly,  and 
the  sympathetic  strongly,  excited,  the  scanty  secretion  (if  there  is 
any)  is  of  sympathetic  type,  thick  and  rich  in  organic  matter.  With 
strong  stimulation  of  both  nerves,  the  secretion,  at  first  plentiful 
and  watery,  soon  diminishes,  even  below  the  amount  obtained  by 
stimulation  of  the  chorda  alone,  because  of  the  diminution  in  the 
blood-flow,  and  therefore  in  the  oxygen- supply,  produced  by  the 
vaso-constrictors  of  the  sympathetic  (Heidenhain).     With  stimula- 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGEST  I  VE  GLANDS      389 

tion  just  strong  enough  to  cause  secretion  when  apphed  separately 
to  either  nerve,  there  is  no  secretion  when  it  is  appUed  simul- 
taneously to  both. 

All  this  refers  to  the  dog.     In  this  animal,  then,  there  seems  to  be 
a  certain  amount  of  physiological  antagonism  between  the  secretory 
action  of  the  two  nerves.     But  it  differs  in  one  respect  from  the 
antagonism  between  their  vaso-motor  fibres;  for  with  strong  stimu- 
lation the  constrictors  of  the  sympathetic  always  swamp  the  dilators 
of  the  chorda,  while  the  secretory  fibres  of  the  chorda  appear  upon 
the  whole  to  prevail  over  those  of  the  sympathetic.     And  in  all 
probability  this  apparent  secretory  antagonism  is  very  superficial, 
and  is  due  largely  to  the  difference  in  the  vaso-motor  effects  of  the 
two  nerves.     For  it  has  been  shown  that,  when  the  blood- flow 
through  the  submaxillary  gland  is  artificially  diminished  by  gradu- 
ated compression  of  its  artery,  stimulation  of  the  chorda  gives  rise 
to  a  thick,  viscid  and  scanty  saliva,  relatively  rich  in  organic  solids 
(Heidenhain).     When  the  amount  of  blood  passing  through  the 
gland  is  made  approximately  the  same  as  during  stimulation  of  the 
sympathetic,  the  chorda  saliva  becomes  practically  identical  in 
composition   with   the    sympathetic    saliva.     This   is   one   reason, 
perhaps  the  chief  one,  why  the  sympathetic,  when  both  nerves  are 
stimulated  together,  without  artificial  interference  with  the  blood- 
supply,  always  appears  to  add  something  to  the  common  secretion 
when  there  is  a  secretion  at  all,  this  something  being  represented 
by  an  increase  in  the  percentage  of  organic  matter.     The  observation 
that  the  sympathetic  effect  persists  after  stimulation  has  been 
stopped,  and  that  excitation  of  the  chorda  after  previous  stimula- 
tion of  the  sympathetic  causes  a  flow  of  saliva  richer  in  organic 
matter  than  would  have  been  the  case  if  the  sympathetic  had  not 
been  stimulated,  has  long  been  considered  a  proof  that  the  secretory 
fibres  of  the  two  nerves  are  widely  different  in  function.     To  explain 
this  result,  Heidenhain  assumed  the  existence  in  the  symipathetic 
of  a  preponderance  of  fibres  concerned  in  the  building  up  in  the 
cells  of  the  organic  constituents  of  the  saliva  (so-called  '  trophic,' 
or,  better,  since  the  word  '  trophic '  is  usually  associated  with  the 
building  up  of  the  bioplasm  itself,  '  trophic-secretory  '  fibres).      It 
would  seem,  however,  that  the  increase  in  organic  constituents  is 
only  realized  when  a  sufficient  time  has  not  been  allowed,  after 
stimulation  of  the  sympathetic,  for  the  normal  circulation  to  become 
re-established  in  the  gland.     The  saliva  obtained  by  stimulation  of 
the  chorda  immediately  after  a  period  of  artificially  diminished 
blood-flow,  without  any  previous  excitation  of  the  sympathetic, 
also  contains  a  surplus  of  organic  matter  (Carlson). 

Indeed,  the  distinction  between  chorda  and  sympathetic  saliva, 
which,  by  taking  account  of  the  parotid  as  well  as  the  submaxillary 
and   sublingual  glands,   has  been  generalized    into   a   distinction 


390  DIGESTION 

between  cerebral  and  sympathetic  saliva,  and  which,  when  the 
vaso-motor  conditions  are  left  out  of  account,  appears  to  hold  good 
in  the  dog  and  the  rabbit,  breaks  down  before  a  wider  induction. 
For  in  the  cat  the  sympathetic  saliva  of  the  submaxillary  gland, 
although  much  more  scanty,  is  more  watery  than  the  chorda  saliva 
(Langley),  which,  however,  is  by  no  means  viscid;  and  the  two 
secretions  differ  far  less  than  in  the  dog.  The  discovery  of  Carlson 
that  the  cat's  cervical  sympathetic  contains  so  many  vaso-dilator 
fibres  for  the  submaxillary  gland  that  the  usual  effect  of  its  stimu- 
lation with  a  weak  interrupted  current  is  a  marked  augmentation 
in  the  blood-flow  affords  an  explanation.  In  accordance  with  this 
functional  similarity,  there  is  a  much  smaller  difference  in  the  action 
of  atropine  on  the  two  sects  of  fibres  in  the  cat  than  in  the  dog, 
although  even  in  the  cat  the  sympathetic  is  less  readily  paralyzed 
than  the  chorda. 

In  their  secretory  action  there  is  not  even  an  apparent  antagonism 
in  the  cat,  with  minimal  stimulation  of  both  nerves,  which  causes 
as  much  secretion  as  would  be  produced  if  both  were  separately 
excited.  Further,  even  in  the  dog,  after  prolonged  stimulation  of 
the  sympathetic,  the  submaxillary  saliva  is  no  longer  viscid,  but 
watery,  the  proportion  of  solids,  and  especially  of  organic  solids, 
being  much  lessened,  as  it  is  also  in  chorda  saliva  after  long  excita- 
tion. When  the  cerebral  nerve  of  the  resting  gland  is  strongly 
excited,  it  is  found  that  up  to  a  certain  limit  the  percentage  of 
organic  matter  in  a  small  sample  of  saliva  subsequently  collected 
during  a  brief  weak  excitation  increases  with  the  strength  of  the 
previous  stimulation;  this  is  also  true  of  the  inorganic  sohds.  But 
there  is  a  striking  difference  when  the  experiment  is  made  on  a  gland 
after  a  long  period  of  activity;  here  increase  of  stimulation  causes 
no  increase  in  the  percentage  of  organic  material,  while  the  inorganic 
solids  are  still  increased.  In  both  cases  the  absolute  quantity  of 
water,  and  therefore  the  rate  of  flow  of  the  secretion,  is  augmented. 

All  this  points  to  the  same  conclusion  as  the  microscopic  appear- 
ances in  the  gland-cells,  that  the  cells  during  rest  manufacture  the 
organic  constituents  of  the  secretion,  or  some  of  them,  and  store 
them  up,  to  be  discharged  during  activity.  The  water  and  the 
inorganic  salts,  on  the  other  hand,  seem  rather  to  be  secreted  on 
the  spur  of  the  moment,  so  to  speak,  and  not  to  require  such 
elaborate  preparation.  And  it  has  been  stated  that  when  the 
chorda  tympani  is  stimulated  with  currents  of  varjnng  strength, 
the  quantity  of  organic  substances  in  small  samples  of  saliva 
collected  from  a  fresh  gland  is  more  nearly  proportional  to  the  rate 
of  secretion  than  is  the  quantity  of  water  and  salts,  which  varies 
also  with  the  blood-supply. 

Lest  the  apparently  insignificant  result  of  artificial  stimulation 
of  the  sympathetic  in  such  animals  as  the  dog  should  cause  its 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     39i 

secretory  action  to  beZaDpraised  at  too  low  a  value,  it  should  be 
remembered  that  in  tne  mtact  body  the  sympathetic  secretory  fibres, 
when  they  are  excited,  arc,  it  may  be  assumed,  excited  independently 
of  the  vaso-constrictors.  and  even  in  conjunction  with  the  vaso- 
dilators of  the  salivary  glands. 

It  is  conceivable  that  such  differences  between  chorda  and 
sympathetic  saliva  as  are  not  accounted  for  by  the  differences  in 
the  blood-flow  during  their  stimulation  are  due,  not  to  the  nerve 
fibres,  but  to  the  end  organs  with  which  they  are  connected;  that 
is,  the  two  nerves  may  supply,  not  the  same,  but  different  gland- 
cells.  And  it  is  well  known  that  even  after  prolonged  stimulation 
of  the  chorda  or  chordo-lingual  alone,  some  alveoli  of  the  dog's 
submaxillary  gland  remain  in  the  '  resting  '  state;  after  stimulation 
of  the  sympathetic  alone,  the  number  of  unaffected  alveoli  is  much 
greater;  while  after  stimulation  of  both  nerves,  few  alveoH  seem 
to  have  escaped  change.  If  there  is  no  essential  difference  between 
the  cranial  and  sympathetic  secretory  fibres,  it  is  easy  to  understand 
that  they  will  be  distributed  to  different  secreting  elements.  The 
supposed  proof  that  there  must  be  some  overlapping  in  the  nerve- 
supply — i.e.,  that  some  cells  must  be  suppHed  from  both  sources, 
since  excitation  of  the  sympathetic  influences  the  amount  of  organic 
material  in  the  saliva  obtained  by  subsequent  stimulation  of  the 
chorda — is,  as  we  have  just  seen,  by  no  means  so  cogent  as  has  been 
assumed.  And,  indeed,  we  know  nothing  of  a  division  of  labour 
between  the  cells  of  a  gland,  except  when  there  are  obvious  anatom- 
ical distinctions.  Thus,  the  submaxillary  gland  in  man  contains 
both  serous  and  mucous  acini,  and  mucin-making  cells  are  scattered 
over  the  ducts  of  most  glands,  and,  indeed,  on  nearly  every  surface 
which  is  clad  with  columnar  epithelium.  In  these  cases  we  cannot 
doubt  that  one  constituent — mucin — of  the  entire  secretion  is  manu- 
factured by  a  portion  only  of  the  cells.  In  the  carchac  glands  of  the 
stomach,  too,  the  ovoid  cells,  in  all  probability,  \deld  the  whole  of 
the  acid  of  the  gastric  juice.  But,  so  far  as  we  know,  every  hepatic 
cell  is  a  liver  in  little.  Every  cell  secretes  fully- formed  bile ;  every 
cell  stores  up,  or  may  store  up,  glycogen.  So  it  is  with  the  secretory 
alveoli  of  the  pancreas,  if  we  consider  the  islands  of  Langerhans  as 
having  no  connection  with  the  alveoh;  one  cell  is  just  like  another; 
all  apparently  perform  the  same  work;  each  is  a  unicellular  pan- 
creas.   (See  p.  624.) 

Paralytic  Secretion. — When  the  ciiorda  tympani  is  divided,  a  slow 
'  paralytic  '  secretion  from  the  submaxillary  gland  begins  in  a  few 
hours,  and  continues  for  a  long  time  accompanied  by  atrophy  of  the 
gland.  There  is  also  a  secretion  of  the  same  kind  from  the  submaxillar^' 
on  the  opposite  side,  but  it  is  less  copious.  This  is  called  the  '  antilytic  ' 
secretion,  which  is  most  pronounced  in  the  first  few  days  after  the 
operation,  and  seems  to  be  a  transient  phenomenon.  It  can  be  at  once 
abolished  by  section  both  of  the  chorda  and  the  sympathetic  on  the 


392  DIGESTION 

corresponding  side,  ana  is  therefore  due  to  impulses  arising  in  the 
central  nervous  system.  The  cause  of  the  paralytic  secretion  has  not 
been  fully  made  out.  If  within  two  or  three  days  of  division  of  the 
chorda  the  sympathetic  on  the  same  side  is  cut,  the  secretion  is  greatly 
diminished  or  stops  altogether;  and  it  is  concluded  that  up  to  this  time 
it  is  maintained  by  impulses  passing  along  the  sympathetic  to  the  gland 
from  the  salivary  centre ,  the  excitability  of  which  has  been  in  some  way 
increased  by  division  of  the  chorda,  possibly  by  some  such  degenerative 
process  in  the  cells  as  the  changes  seen  in  cerebro-spinal  motor  cells 
whose  axons  have  been  divided  (p.  830).  This  may  also  account  for  the 
antilytic  secretion.  But  if  section  of  the  sympathetic  is  not  performed 
for  several  days,  it  has  no  effect  on  the  paralytic  secretion,  which  at 
this  stage  seems  to  depend  on  local  changes  in  or  near  the  gland  itself, 
leading  to  a  mild  continuous  excitation  of  those  nerve-cells  on  the 
course  of  the  fibres  of  the  chorda  to  which  reference  has  already  been 
made.  Section  of  the  sympathetic  alone  causes  neither  secretion  nor 
atrophy,  nor  does  removal  of  the  superior  cervical  ganglion.  The 
histological  characters  of  the  gland-cells  during  paralytic  secretion  are 
those  of  '  rest.' 

Reflex  Secretion  of  Saliva. — The  reflex  mechanism  of  salivary 
secretion  is  very  mobile,  and  easily  set  in  action  by  physical  and 
mental  influences.  It  is  excited  normally  by  impulses  which  arise 
in  the  mouth,  especially  by  the  contact  of  food  with  the  buccal 
mucous  membrane  and  the  gustatory  nerve-endings.  The  mere 
mechanical  movement  of  the  jaws,  even  when  there  is  nothing 
between  the  teeth,  or  only  a  bit  of  a  non-sapid  substance  like  india- 
rubber,  causes  some  secretion.  The  vapour  of  ether  gives  rise  to  a 
rush  of  saliva,  as  does  gargling  the  mouth  with  distilled  water. 
The  smell,  sight,  or  thought  of  food,  and  even  the  thought  of  saHva 
itself,  may  act  on  the  salivary  centre  through  its  connections  with 
the  cerebrum,  and  make  '  the  teeth  water.'  A  copious  flow  of 
sahva,  reflexly  excited  through  the  gastric  branches  of  the  vagus, 
is  a  common  precursor  of  vomiting.  The  introduction  of  food  into 
the  stomach  also  excites  salivary  secretion. 

The  researches  of  Pawlow  and  his  pupils  have  shown  that  the 
salivary  glands  are  not  excited  indifferently  by  everything  which 
comes  into  contact  with  the  buccal  mucous  membrane.  A  remark- 
able adaptation  exists  between  the  properties  of  food  or  foreign 
bodies  introduced  into  the  mouth  and  their  effects  upon  the  secre- 
tion of  saliva.  When  solid  dry  food  is  given  to  a  dog  saliva  is 
copiously  poured  out ;  much  less  is  secreted  when  the  food  is  moist. 

Acids  or  salts  induce  an  abundant  flow,  in  order  that  they  may 
be  neutralized,  diluted  or  washed  out  of  the  mouth.  In  this  case 
a  watery  liquid,  poor  in  mucin,  flows  from  the  mucous  glands. 
Mucin  is  a  lubricant  to  facilitate  the  swallowing  of  soHd  food,  and 
here  it  could  be  of  no  use.  When  clean  pebbles  are  put  in  the  dog's 
mouth  the  animal  may  try  to  chew  them,  but  eventually  ejects 
them.  Either  no  saliva  or  very  little  is  secreted,  since  it  could 
not  aid  in  their  expulsion.     If,  however,  the  very  same  stones  are 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     393 

reduced  to  sand  and  again  introduced  into  the  animal's  mouth, 
saliva  is  plentifully  secreted  to  wash  it  out. 

The  serous  and  mucous  salivary  glands  are  not  necessarily  excited 
by  the  same  food  materials,  and  here  again  we  can  trace  an  astonish- 
ingly exact  adaptation.  A  permanent  parotid  or  submaxillary 
fistula  can  easily  be  made  in  a  dog  by  freeing  Stenson's  or  Wharton's 
duct  from  the  surrounding  mucous  membrane  for  a  Ifttle  distance, 
bringing  the  natural  orifice  of  the  duct  out  through  a  small  wound 
in  the  cheek,  and  stitching  it  in  position  there.  When  it  is  desired 
to  collect  saliva,  the  wide  end  of  a  funnel-shaped  tube,  whose  stem 
is  bent  so  as  to  hang  vertically,  can  be  attached  by  a  little  shellac 
of  low  melting-point  to  the  skin  around  the  orifice  of  the  duct  and 
at  some  distance  from  it,  and  on  the  narrow  end  can  be  hung  a  small 
graduated  tube,  into  which  the  saliva  drops.  When  fresh  meat  is 
given  to  the  animal  little  or  no  parotid  saliva  is  secreted,  while  a 
copious  flow  takes  place  from  the  submaxillary  gland,  mucin  being 
required  to  lubricate  it  for  deglutition,  while  water  is  not  specially 
needed.  But  if  the  meat  is  in  the  form  of  a  dry  powder  the  parotid 
pours  out  a  plentiful  secretion,  while  the  submaxillary  also  secretes 
a  fluid  relatively  rich  in  mucin.  The  same  difference  is  seen  between 
fresh  moist  bread  and  dry  bread.  The  afferent  nerve-endings  from 
which  impulses  are  carried  to  the  reflex  centres  (or  the  portions  of 
the  salivary  centre)  which  preside  over  the  various  salivary  glands 
must  possess  the  power. of  very  delicate  selection  as  regards  the 
kinds  of  stimulation  by  which  they  are  affected.  The  mere  relish 
of  the  animal  for  the  different  kinds  of  food  plays  but  a  small  part. 
Most  dogs  display  a  much  livelier  interest  in  a  piece  of  meat  than 
in  a  piece  of  dry  biscuit,  yet  it  is  the  biscuit  which  excites  the  parotid 
to  activity. 

The  sight  of  dry  food  causes  an  abundant  flow  of  watery  saliva 
from  the  parotid,  and  a  flow  of  fluid  rich  in  mucin  from  the  sub- 
maxillary. Various  uneatable  substances,  including  substances 
which  in  contact  with  the  mucous  membrane  of  the  mouth  produce 
strong  and  disagreeable  stimulation  of  it,  and  excite  disgust,  cause 
also,  when  viewed  from  a  distance,  secretion  by  all  the  salivary 
glands;  but  the  submaxillary  saliva,  as  ought  to  be  the  case  for 
substances  unfit  for  food,  and  therefore  not  destined  to  be  swallowed, 
is  poor  in  mucin.  When  the  animal  is  shown  pebbles  and  sand 
the  phenomena  are  qualitatively  the  same  as  when  they  are  put 
into  its  mouth — the  glands  remaining  inactive  in  presence  of 
the  pebbles,  but  secreting  plentifully  at  sight  of  the  sand.  In 
short,  the  same  adaptation  is  observed  in  the  case  of  the  so-called 
psychical  secretion  as  when  the  stimulating  substances  act  directly 
upon  the  endings  of  the  afferent  salivary  nerves  in  the  buccal 
mucous  membrane.  It  is  further  worthy  of  note  that  when  the 
animal  is  hungry  the  psychical  secretion  is  most  copious  and  most 


394  DIGESTION 

easily  obtained.  After  a  full  meal  it  cannot  be  excited  at  all. 
When  food  (or  other  exciting  substance)  is  repeatedly  shown  to  a 
fasting  animal  the  reaction  becomes  each  time  weaker,  and  finally 
the  glands  cease  to  respond.  All  that  is  then  necessary  to  restore 
the  reaction  is  to  put  into  the  animal's  mouth  a  little  of  the  food 
(or  other  object).  When  it  is  now  shown  it  at  a  distance  the  ordinary 
effect  follows  promptly.  This  indicates  that  the  condition  of  the 
salivary  centre  exercises  an  important  influence  upon  the  psychical 
secretion,  its  excitability  to  the  weaker  stimulus  set  up  by  the  sight 
of  the  object  being  increased  by  the  stronger  reflex  stimulation 
coming  directly  from  the  mouth.  In  the  condition  of  satiety  the 
inexcitability  of  the  centre  may  be  due  to  the  action  of  food- 
products  in  the  blood. 

In  most  animals  and  in  man  the  activity  of  the  large  salivary 
glands  is  strictly  intermittent.  But  the  smaller  glands  that  stud 
the  mucous  membrane  of  the  mouth  never  entirely  cease  to  secrete, 
and  the  same  is  the  case  with  the  parotid  in  ruminant  animals. 

The  centre  is  situated  in  the  medulla  oblongata,  stimulation  of 
which  causes  a  flow  of  saliva.  The  chief  afferent  paths  to  the 
saHvary  centre  are  the  lingual  branch  of  the  fifth  and  the  glosso- 
pharyngeal ;  but  stimulation  of  many  other  nerves  may  cause  reflex 
secretion  of  saHva.  In  experimental  reflex  stimulation,  the  sole 
efferent  channel  seems  to  be  the  cerebral  nerve-supply  of  the  glands. 
After  section  of  the  chorda,  no  reflex  secretion  by  the  submaxillary 
gland  can  be  caused,  although  the  sympathetic  remains  intact. 

It  was  alleged  by  Bernard  that,  after  division  of  the  chordo- 
lingual,  a  reflex  secretion  could  be  obtained  from  the  submaxillary 
gland  by  stimulating  the  central  end  of  the  cut  hngual  nerve  between 
the  so-called  submaxillary  ganglion  and  the  tongue,  the  ganglion 
being  supposed  to  act  as  '  centre.'  It  has  been  shown,  however,  that 
this  is  not  a  true  reflex  effect,  but  is  due  to  the  excitation  of  certain 
(recurrent)  secretory  fibres  of  the  chorda  that  run  for  some  distance 
in  the  lingual,  then  bend  back  on  their  course  and  pass  to  the  gland. 
It  may  be  in  part  a  pseudo-  or  axon-reflex  (p.  885),  eficited  by 
excitation  of  efferent  fibres,  which  send  branches  to  some  of  the 
ganghon-cells. 

The  salivary  centre  can  also  be  inhibited,  especially  by  emotions 
of  a  painful  kind — for  instance,  the  nervousness  which  often  dries 
up  the  saliva,  as  well  as  the  eloquence,  of  a  beginner  in  public 
speaking,  and  the  fear  which  sometimes  made  the  medieval  ordeal 
of  the  consecrated  bread  pick  out  the  guilty. 

In  rare  cases  the  reflex  nervous  mechanism  that  governs  the 
salivary  glands  appears  to  completely  break  down;  and  then  two 
opposite  conditions  may  be  seen — xerostomia,  or  '  dry  mouth,'  in 
which  no  saliva  at  all  is  secreted,  and  chronic  ptyalism,  or  hydro- 
stomia,  where,  in  the  absence  of  any  discoverable  cause,  the  amount 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     395 

of  secretion  is  permanently  increased.     Both  conditions  are  said 
to  be  more  common  in  women  than  in  men. 

The  Influence  of  Nerves  on  the  Gastric  Glands. — Like  saliva,  gastric 
juice  is  not  secreted  continuously,  except  in  animals  such  as  the 
rabbit,  whose  stomachs  are  never  empty.  The  normal  and  most 
efficient  stimulus  is  the  eating  of  food  and  its  presence  in  the 
stomach.  Mechanical  stimulation  of  the  gastric  mucous  membrane 
with  a  non-digestible  substance,  such  as  a  feather  or  a  glass  rod, 
causes  secretion  of  mucus,  but  not  of  gastric  juice.  But  the 
observations  mentioned  above  on  the  difference  of  response  of  the 
salivary  glands  to  different  substances  suggest  that  the  local  mechan- 
ical stimulation  of  the  food  on  the  gastric  glands  may  be  more 
effective.  There  is  also  at  first  thought  much  to  indicate  that  the 
gastric  glands  are  stimulated  chemically  in  a  more  direct  manner 
than  the  salivary  glands  by  the  local  action  of  food  substances 
reaching  the  cells  by  a  short-cut  from  the  cavity  of  the  stomach, 
or  in  a  more  roundabout  way  by  the  blood.  And  it  might  be  very 
plausibly  argued  that  the  gastric  glands  are  favourably  situated 
for  direct  stimulation,  while  the  large  salivary  glands  are  not;  and 
that  the  great  function  of  saliva  being  to  aid  deglutition,  an  almost 
momentary,  and  at  the  same  time  a  perilous  act,  it  is  necessary  to 
provide  by  a  nervous  mechanism  for  an  immediate  rush  of  secre- 
tion at  any  instant,  while  it  is  not  important  whether  the  gastric 
juice  is  poured  out  a  little  sooner  or  a  little  later,  and  therefore  it  is 
left  to  be  called  forth  by  the  more  tardy  and  haphazard  method  of 
local  action.  Nevertheless,  on  looking  a  little  closer,  we  find  that 
this  does  not  exhaust  the  subject,  and  that  the  gastric  secretion 
can  be  influenced  by  events  taking  place  in  distant  parts  of  the 
body,  just  as  the  salivary  secretion  can.  In  a  boy  whose  oesophagus 
was  completely  closed  by  a  cicatrix,  the  result  of  swallowing  a  strong 
alkali,  and  who  had  to  be  fed  by  a  gastric  fistula,  it  was  found 
that  the  presence  of  food  in  the  mouth,  and  ev&n.  the  sight  or  smell 
of  food,  caused  secretion  of  gastric  juice  (Richet). 

Here  there  must  have  been  some  nervous  mechanism  at  work. 
The  secretion  cannot  have  been  excited  by  the  direct  action  of 
absorbed  food-products  circulating  in  the  blood — an  explanation 
which  might  be  given,  though  an  insufficient  one,  of  the  secretion 
seen  in  an  isolated  portion  of  the  cardiac  end  of  the  stomach  during 
the  digestion  of  food  in  the  rest.  The  efferent  nervous  channels 
through  which  these  effects  are  produced  have  been  defined  by 
Pawlow's  experiments  on  dogs.  He  first  made  a  gastric  fistula, 
then  a  few  days  afterwards  divided  the  oesophagus  through  a 
wound  in  the  neck,  and  stitched  the  two  cut  ends  to  the  edges  of 
the  wound.  After  the  animals  had  recovered,  it  was  observed  that 
when  meat  was  given  to  them  by  the  mouth,  a  copious  secretion  of 
gastric  juice  followed  in  five  or  six  minutes,  notwithstanding  the 


396 


DIGESTION 


Pylorus 


sophagus 


fact  that  in  this  '  sham  feeding  '  the  food  immediately  escaped  from 
the  opening  in  the  upper  portion  of  the  divided  oesophagus.  Much 
the  same  result  was  seen  when  the  food  was  simply  shown  to  the 
animal.  Indeed,  when  a  hungry  animal  is  tempted  with  the  sight 
of  meat,  the  flow  of  gastric  juice,  always  occurring  after  a  latent 
period  of  five  or  six  minutes,  may  be  even  greater  than  with  sham 
feeding.  Division  of  the  splanchnic  nerves  had  no  effect  on  this 
reflex  secretion,  while  it  could  not  be  obtained  after  division  of  both 
vagi  below  the  origin  of  their  cardiac  and  pulmonary  branches,  by 
which  disturbance  of  the  heart  and  respiration  are  avoided. 
Further,  stimulation  of  the  peripheral  end  of  the  vagus  in  the  neck* 
caused  secretion.  These  experiments  show  that  secretory  fibres 
for  the  gastric  glands  run  in  the  vagi.     It  is  probable  that  the  vagi 

also    contain 

efferent     fibres 

which     inhibit 

-, .^^  _         _ the   gastric 

P/ej<us  gastncus/'  VUT  _^a^        /    '"''^''"■'^''^""'^"^  ciprrpfinn        Thp 

anterior  vagi./  ^     ^   j       .^^^^^^^^Mf\     I    posterior  vagi      bccicLiun.       i  iic 

excitation  of 
the  secretory 
fibres  is  not 
produced  re- 
flexly  by  the 
processes  of 
mastication 
and  deglutition 
as  such.  Di- 
lute acid  is  the 
most  powerful 
chemical  stim- 
ulus for  the 
buccal  mucous 
membrane,  and 

when  it  is  introduced  into  the  mouth  of  a  dog  with  a  double 
oesophageal  and  gastric  fistula,  an  abundant  secretion  of  saliva  at 
once  ensues.  But  no  matter  how  long  the  animal  continues  to 
swallow  the  mixture  of  saliva  and  acid,  no  gastric  juice  is  formed. 
The  same  is  the  case  in  sham  feeding  with  salt,  pepper,  mustard, 
smooth  stones,  and  even  extract  of  meat.  It  is  the  desire  for  food 
— the  appetite,  as  we  call  it — and  the  feeling  of  satisfaction  associa- 
ated  with  eating  food  that  the  animal  relishes,  which  is  the  efficient 
cause  of  the  gastric  secretion  in  sham  feeding.  The  more  eagerly 
the  dog  eats,  the  greater  is  the  flow  of  gastric  juice. 

*  The  nerve  was  not  stimulated  till  a  few  days  after  the  section,  so  as  to 
allow  the  cardio-inhibitory  fibres  to  degenerate.  Otherwise  the  heart  would 
have  been  stopped  by  the  stimulation. 


Fig.  i6i. — Pawlow's  Stomach  Pouch.  AB.  line  of  incision; 
C,  flap  for  forming  the  stomach  pouch.  At  the  base  of  the 
flap  the  serous  and  muscular  coats  are  preserved,  and  only 
the  mucous  membrane  divided,  so  that  the  branches  of  the 
vagus  going  to  the  pouch  are  not  severed. 


Muscularis 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     397 

Pawlow  also  performed  the  converse  experiment.     In  dogs  in 
which  a  pouch  had  been  isolated  from  the  stomach  and  made  to 
open  to  the  exterior  by  the  surgical  procedure  illustrated  in  Figs.  161 
and  162,  he  introduced  into  the  large  stomach,  without  the  animal's 
knowledge,  food  of  various  kinds.     This  is  best  done  in  a  sleeping 
dog.     The  secretion  of  gastric  juice,  both  in  the  main  stomach  and 
in  the  pouch  or  miniature  stomach,  which  is  known  in  a  great 
variety  of  conditions  to  present  an  exact  picture  of  the  process  of 
secretion  in  the  large,  is  markedly  delayed  and  scanty  when  it  does 
appear.     Bread  and  coagulated  egg-white  did  not  yield  a  single 
drop   during 
the  first  hour 
or  more.   Raw 
flesh  excited  a 
secretion,  but 
after  an  inter- 
val of  fifteen 
to    forty  -  five 
minutes,      in- 
stead   of    five 
or  six  to  ten, 
as     in     sham 
feeding.  It  was 
very  scanty 
during    the 
first    hour 
(only    o  n  e  - 
third  the  nor- 
mal amount), 
and  possessed 
a  very  low  di- 
gestive power. 
The    impor- 
tance   of   the 
psychical  ele- 
ment is  shown  by  the  fact  that  in  one  dog,  which,  after  a  weighed 
amount  of  meat  had  been  introduced  into  its  stomach  (without  its 
knowledge),  received  a  sham  meal  of  meat,  the  amount  of  protein 
digested  after  one  and  a  half  hours  was  five  times  greater  than  in 
another  animal  treated  exactly  in  the  same  way,  except  that  the  sham 
meal  was  omitted.     But  even  after  division  of  the  vagi,  gastric  secre- 
tion is  still  caused  by  the  introduction  of  various  substances  into  the 
stomach,  especially  water  and  meat  extract.     The  active  substances 
in  the  meat  extract  are,  for  the  most  part,  insoluble  in  alcohol. 
Kreatin  is  inactive.     It  is  in  virtue  of  these  substances  that  raw 
meat  placed  directly  in  the  stomach  causes  some  secretion  after  a 


Fig.  162. — Pawlow's Stomach  Pouch.     S,  the  completed  pouch; 
V,  cavity  of  stomach. 


398  DIGESTION 

time.  Milk  and  gelatin  solution  are  also  direct  excitants  of  gastric 
secretion  apart  from  the  water  in  them.  Starch,  fat,  and  egg-white 
are  totally  inert.  After  section  of  both  vagi  in  dogs,  no  marked 
qualitative  or  quantitative  changes  have  been  observed  in  the 
gastric  juice.  The  secretion  caused  by  the  presence  of  food  in  the 
stomach  is  still  obtained  when,  in  addition  to  the  vagi,  all  other 
nerves  which  can  possibly  connect  the  central  nervous  system  with 
the  organ  have  been  severed  and  the  sympathetic  abdominal 
plexuses  have  been  destroyed  (Popielski).  We  must  therefore  sug- 
pose  that  the  gastric  glands,  while  normally  under  the  control  of  a 
nervous  mechanism  in  the  upper  portion  of  the  cerebro- spinal  axis 
whose  efferent  fibres  run  in  the  vagi,  are  also  capable  of  being  locally 
stimulated  through  the  peripheral  ganglia  in  the  stomach  walls  or 
the  chemical  action  of  the  products  of  digestion  absorbed  into  the 
blood.  Edkins  showed  that  the  injection  of  food  substances  or  the 
products  of  their  digestion  (broth,  dextrin,  peptone)  or  of  acid  into 
the  blood  caused  no  secretion  of  gastric  juice,  while  the  injection 
of  an  extract  of  the  pyloric  mucous  membrane,  made  by  boiling  it 
with  water,  acid,  or  peptone,  excited  a  certain  amount  of  secretion. 
He  therefore  concluded  that  the  secondary  secretion  of  gastric  juice 
is  determined,  not  by  local  stimulation  of  a  reflex  mechanism  in  the 
gastric  wall,  but  by  the  production  in  the  mucous  membrane  of  the 
pyloric  end  of  a  chemical  substance,  the  gastric  secretin  or  gastric 
hormone,*  which  is  absorbed  by  the  blood,  and  acts  as  an  excitant 
to  all  the  gastric  glands.  The  cardiac  mucosa  was  found  incapable 
of  forming  this  substance. 

It  is  not  to  be  imagined  that  the  '  psychical '  secretion  and  the 
secretion  called  forth  by  the  direct  action  of  the  food  or  food- 
products  in  the  stomach  perform  independent  offices.  They  can, 
in  various  instances,  be  shown  to  supplement  each  other.  For 
example,  not  more  than  one-half  or  one-third  of  the  gastric  juice 
secreted  during  the  digestion  of  bread  or  boiled  egg-albumin  can 
be  ascribed  to  the  psychic  effect.  Yet  these  substances,  when 
introduced  directly  into  the  stomach,  cause  practically  no  secretion. 
We  must  suppose  that  during  the  digestion  of  the  bread  and  albu- 
min by  the  psychically  secreted  juice  certain  products  analogous  to 
those  in  the  meat  extract  are  formed,  which  act  as  chemicd  excitants 
of  the  local  secretory  apparatus.  The  psychic  juice  is  indispensable 
in  this  case  to  start  the  process,  '  to  set  the  stove  ablaze,'  as  Pawlow 
puts  it.  In  the  case  of  meat  it  is  not  indispensable,  since  the  meat 
can  chemically  excite  the  gastric  glands;  but  it  greatly  hastens  the 
process  of  digestion.     These   facts  emphasize  the  importance  of 

*  '  Hormone  '  (from  bpfj.au,  I  arouse  or  excite)  is  the  name  given  to  a  sub 
stance  which,  carried  by  the  blood  from  the  place  where  it  is  formed,  acts  as 
a  chemical  messenger  in  exciting  the  activity  of  some  more  or  less  distant 
organ.  The  classical  example  is  the  pancreatic  secretin  which,  manufactured 
in  the  intestinal  mucosa,  excites  the  secretion  of  the  pancreatic  juice. 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     399 

appetite  in  digestion,  a  truism  in  treatment  which  thus  receives 
for  the  first  time  a  rational  explanation.  The  influence  of  good- 
humour  upon  nutrition,  which  experience  has  crystallized  into  the 
proverb  '  Laugh  and  grow  fat,'  has  also  been  shown  to  depend — 
in  great  part,  at  least — upon  a  beneficial  action  on  the  digestive 
functions,  both  motor  and  chemical.  The  movements  of  a  cat's 
stomach  and  intestines  have  been  observed  to  cease  when  the 
animal  became  angry  or  e.xcited  by  unpleasant  emotions;  and  in  a 
dog  whose  gastric  glands  were  pouring  out  a  copious  psychical 
secretion  in  response  to  a  sham  meal,  secretion  stopped  abruptly 
when  the  animal's  wrath  was  awakened  by  what  is  probably  to  the 
normal  dog  the  most  specifically '  adequate '  stimulus  for  the  emotion 
of  anger — the  sight  of  a  cat  which  he  was  restrained  from  chasing. 

By  means  of  experiments  with  the  miniature  stomach  it  has  been 
further  shown  that  each  kind  of  food  has  its  own  characteristic 
curve  of  gastric  secretion.  With  flesh  diet  the  maximum  rate  of 
secretion  occurs  during  the  first  or  second  hour,  and  in  each  of  the 
first  two  hours  the  quantity  of  juice  furnished  is  approximately 
the  same.  With  bread  diet  we  have  always  a  sharply-indicated 
maximum  in  the  first  hour,  and  with  milk  a  similar  one  during  the 
second  or  the  third  hour  (Fig.  163).  The  juice  secreted  on  different 
diets  also  differs  in  digestive  power — i.e.,  in  the  amount  of  protein 
which  a  given  quantity  of  it  will  digest  in  a  given  time.  '  Bread 
juice  '  is  much  stronger  in  ferment  than  '  meat  juice,'  and  '  meat 
juice '  somewhat  stronger  than  '  milk  juice '  (Fig.  164).  But 
'  meat  juice  '  has  a  higher  acidity  than  '  bread  juiee,'  '  milk  juice  ' 
being  intermediate.  These  differences  do  not  necessarily  indicate 
that  the  gastric  mucous  membrane  responds  in  a  specific  way  to 
each  kind  of  food  substance,  as  suggested  by  Pawlow.  They  may 
depend  on  several  circumstances,  and  particularly  on  this — that  the 
quantity,  though  not  the  quality,  of  the  psychical  or  '  appetite  ' 
juice  is  related  to  the  relish  with  which  the  animal  eats  the  food. 
The  products  formed  in  the  digestion  of  the  different  foods  by  the 
psychical  juice  may  therefore  be  different  in  nature  and  amount, 
and  thus  the  quantity  of  the  gastric  hormone  which  determines  the 
secondary  secretion  may  vary  with  the  food. 

The  young  mammal,  like  the  adult,  secretes  gastric  juice  before 
the  food  reaches  the  stomach.  In  puppies  from  one  to  eighteen 
days  old  sham  feeding  (sucking  the  teats  of  the  mother  after  an 
esophageal  fistula  has  been  made  in  the  younger  animals  and  a 
double  oesophageal  and  gastric  fistula  in  the  older)  causes  a  lii|uitl 
with  the  properties  of  gastric  juice  to  gather  in  the  stomach.  This 
power,  then,  is  a  congenital  one.  The  individual  does  not  gain  it 
by  experience;  it  comes  into  the  world  with  him  (Cohnheim). 
.  The  Influence  of  Nerves  on  the  Pancreas. — Like  the  stomach,  the 
pancreas  receives  secretory  fibres  through  the  vagus.     These  are 


400 


DIGESTION 


Hours 
12 


10 


1234-5678    •     23456789  10   123456 


iMIIIIIitlllll 

^ ^. . '^ . 


Flesh,  200  grm. 


Bread,  200  grm. 


Milk,  600  c.c 


Fig.  163. 


-Rate  of  Secretion  of  Gastric  Juice  with  Diets  of  Meat, 
Bread,  and  Milk  (Pawlow). 


probably  connected  with  a  reflex  centre  in  the  medulla  oblongata. 
It  has  long  been  known  that  when  the  medulla  is  stimulated  a  flow 
of  pancreatic  juice  is  occasionally  set  up,  or  is  increased  if  already 
going  on.  The  same  is  true  when  the  vagus  is  stimulated  in  the 
ordinary  way  in  the  neck.     But  the  experiment  often  failed,  for 

the  pancreas 
is  peculiarly 
susceptible 
to  circulatory 
disturbances, 
and  stimula- 
tion of  the 
bulb  or  the 
vagus  may 
interfere  with 
the  blood- 
flow  through 
the  gland  by 
exciting  its 
vaso-con- 
strictor  fibres  or  causing  inhibition  of  the  heart.  These  disturbing 
influences  may  be  avoided,  as  Pawlow  has  shown,  by  stimulating  the 
vagus,  three  or  four  days  after  dividing  it,  with  slowly-recurring 
stimuli  (induction  shocks  or  light  blows  from  a  small  hammer 
worked  by  an 
electro  -  mag- 
net at  the 
rate  of  about 
one  in  the 
second).  The 
secretory 
fibres  are  still 
susceptible  of 
excitation, 
while  the  car- 
dio-inhibitory 
fibres,  which 
degenerate 
more  rapidly, 
are  almost  or 
altogether  in- 
excitable,  and  the  vaso-constrictors  are  but  'little  affected  by 
these  slow  rhythmical  stimuli,  which  excite  the  secretory  nerves 
(p.  173).  A  pancreatic  fistula  has  previously  been  estabhshed  by 
excising  a  small  portion  of  the  duodenal  wall  containing  the  open- 
ing of  the  pancreatic  duct,  closing  the  intestine  by  sutures,  and 


Hours  I    2 
10.0 


345678234     5676 


2    3 


6.0 


6,0 


4,0 


2.0 


7^^^; 

^  N^ 

^     i              ^    y 

^   ^vv^            5    / 

—^    \r                     \-^^ 

, . .        .,,.  ,. , 

Flesh,  200  grm. 


Bread,  200  grm. 


Milk,  600  c.c. 


Fig.  164. — Digestive  Power  of  Gastric  Juice  (Pawlow).  The 
digestive  power  of  the  juice,  as  measured  by  the  length  of  the 
protein  column  digested  in  Mett's  tubes,  is  represented  hour  by 
hour,  with  diets  of  flesh,  bread,  and  milk. 


I  NFL  UENCE  OF  NER  VO  US  S  YSTEM  ON  DICE  ST  I  VE  GLA  NDS      4c  i 


stitching  the  orifice  of  the  duct  into  the  abdominal  wound.  On 
stimulation  of  tlie  vagus  the  juice  will  begin  in  two  to  three  minutes 
to  drop  from  a  cannula  in  the  duct,  and  will  continue  to  flow  for 
several  minutes  after  cessation  of  the  stimulus.  The  sympathetic 
also  contains  secretory  fibres  for  the  pancreas.  Efferent  fibres 
which  inhibit  the  secretion  have  been  also  discovered  in  the  vagus. 
Their  presence  may  be  most  clearly  demonstrated  when  that  nerve 
is  stimulated  during  the  flow  of  pancreatic  juice  excited  by  the 
introduction  of  dijute  acid  into  the  duodenum.  Stimulation  of  the 
central  end  of  the  vagus  and  of  the  other  nerves  is  capable  of 
reflexly  inhibiting 
the  pancreatic  secre- 
tion. Painful  im- 
pressions have  a 
strong  inhibitory  in- 
fluence. This  is  one 
of  the  reasons  why 
many  observers 
failed  to  detect  the 
secretory  nerves. 
The  inhibition 
caused  by  vomiting 
is  probably  due  to 
impulses  ascending 
the  vagus.  It  i s  pos- 
sible that  through 
these  nervous  chan- 
nels the  pancreatic 
secretion  is  affected 
by  the  psychical  con- 
ditions connected 
with  eating  and  the 
desire  for  food,  just 
as  in  the  case  of  the 
gastric  secretion ;  but 
our  information  on 
this  subject  is  scantier  and  less  precise.  A  flow  of  juice  may  un- 
doubtedly take  place  within  three  or  four  minutes  after  food  is  taken, 
but  it  is  not  quite  certain  whether  this  is  not  determined  by  the 
passage  of  some  of  the  acid  gastric  contents  into  the  duodenum. 

Secretin. — ^\Ve  have  already  referred  to  the  fact  that  pancreatic 
secretion  is  excited  by  the  presence  of  acid  in  the  duodenum.  The 
mechanism  of  this  action  is  of  great  interest.  Two  or  three  minutes 
after  the  introduction  of  04  per  cent,  hydrochloric  acid  into  the 
duodenum,  pancreatic  juice  begins  to  flow.  A  similar  effect  is  seen 
when  the  acid  is  placed  in  the  jejunum,  but  not  when  it  is  injected 

26 


Fig.  165. — Secretion  of  Pepsin.  C  shows  the  quantity 
of  pepsin(ogen)  in  the  mucous  membrane  of  the 
cardiac  end  of  the  stomach  at  different  times  during 
digestion;  P,  the  quantity  of  pepsin(ogen)  in  the 
mucous  membrane  of  the  pyloric  end;  S,  the  quantity 
of  pepsin  in  the  secretion  of  the  cardiac  glands.  The 
numbers  marked  along  the  horizontal  axis  are  hours 
since  the  last  meal.  About  five  hours  after  the 
meal,  S  reaches  its  maximum.  From  the  very  be- 
ginning of  the  meal  C  falls  steadily  down  to  the 
tenth  hour,  and  then  begins  to  rise — i.e.,  the  gland- 
cells  of  the  cardiac  end  of  the  stomach  become 
poorer  in  pepsin(ogen)  as  secretion  proceeds. 


402  DIGESTION 

into  the  lower  part  of  the  ileum.  It  is  obtained  as  strongly  and  as 
promptly  from  an  isolated  loop  of  intestine  when  all  the  nerves 
passing  to  it  have  been  cut,  and  the  solar  plexus  extirpated,  and  also 
after  the  administration  of  atropine,  which  paralyzes  the  endings  of 
secretory  nerves  elsewhere.  The  secretion  accorlingly  does  not 
depend  upon  a  local  reflex  mechanism,  with  its  afferent  endings  in 
the  intestinal  mucous  membrane,  but  upon  some  substance  which  is 
carried  to  the  pancreas  by  the  blood,  and  acts  directly  upon  its  cells. 
This  substance  is  not  the  acid,  for  the  injection  of  04  per  cent, 
hydrochloric  acid  into  the  blood  produces  no  effect  upon  the  pan- 
creas. It  has  been  shown  by  Bayliss  and  Starling  that  the  exciting 
substance  is  a  diffusible  body  of  low  molecular  weight,  probably  of 
organic  nature,  but  not  a  protein,  which  they  call  secretin.  It  is 
soluble  in  alcohol  or  alcohol  and  ether,  and  is  not  destroyed  by 
boiling.  It  is  produced  in  the  mucous  membrane  of  the  jejunum  or 
duodenum  on  exposure  to  dilute  hydrochloric  acid.  Extracts  of 
mucous  membrane  so  treated  cause  a  copious  pancreatic  secretion, 
and  a  smaller  secretion  of  bile,  when  injected  in  small  quantities  into 
the  blood  of  animals  in  which  no  such  secretion  is  taking  place,  but 
have  no  influence  on  any  other  gland.  At  the  same  time  the  arterial 
blood-pressure  falls  somewhat.  The  substance  which  produces  the 
fall  of  blood-pressure  is  different  from  secretin,  since  acid  extracts 
of  the  lower  end  of  the  ileum,  which  have  no  effect  on  the  flow  of  pan- 
creatic juice,  diminish  the  blood-pressure.  A  precursor  of  secretin, 
called  prosecretin,  exists  in  the  intestinal  mucous  membrane,  and 
can  be  extracted  from  it  by  physiological  salt  solution.  It  does  not 
affect  the  pancreatic  secretion.  By  boiUng  or  by  the  action  of  acid 
secretin  is  split  off  from  it.  Pro-secretin  is  most  abundant  in  the 
duodenum,  and  diminishes  as  we  pass  down  the  intestine. 

Secretin  is  very  widespreaci  in  the  animal  kingdom.  In  the 
monkey,  dog,  cat,  rabbit,  man,  ox,  sheep,  pig,  squirrel,  goose, 
tortoise,  salmon,  dog-fish,  and  skate  evidence  of  its  presence  has 
been  obtained.  The  secretin  of  one  animal  will  excite  a  flow  of  pan- 
creatic juice  in  an  animal  of  a  different  kind  as  well  as  in  one  of  the 
same  kind.  In  normal  digestion  secretin  is  formed  under  the 
influence  of  the  acid  chyme,  not  in  the  stomach,  but  after  it  has 
passed  into  the  duodenum.  The  passage  of  the  chyme  through  the 
pylorus,  as  previously  mentioned  (p.  321),  is  regulated  by  the  re- 
action of  the  duodenal  contents,  as  well  as  by  the  consistence  of  the 
gastric  contents.  So  long  as  the  liquid  in  the  duodenum  is  acid,  the 
pylorus  remains  closed.  As  soon  as  the  first  small  portion  of  acid 
chyme  ejected  from  the  stomach  has  been  neutralized  by  the  in- 
creased secretion  of  the  pancreatic  juice  and  the  outpouring  of  bile 
from  the  gall-bladder  in  response  to  the  stimulus  of  the  acid,  the 
pylorus  opens  again. 

According  to  Pawlow,  certain  food  substances,  notably  fat,  and 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     403 

water  stimulate  the  pancreatic  secretion,  and  with  great  promptness, 
even  before  any  acid  has  been  produced  in  the  stomach,  and  there- 
fore before  any  can  have  passed  into  the  duodenum.  Possibly  this 
effect  is  ehcited  through  the  long  reflex  paths  already  described  as 
running  in  the  vagi  or  through  a  local  nervous  mechanism,  which, 
although  it  does  not  take  part  in  the  excitation  of  the  pancreatic 
secretion  by  acid,  may  yet  exist  for  the  performance  of  other  offices. 
It  is  more  probable,  however,  that  it  is  due  to  the  passage  of  some  of 
the  gastric  contents  through  the  pylorus;  for  when  oil  is  introduced 
into  the  small  intestine,  it  causes  the  production  of  secretin,  although, 
unlike  dilute  acid,  it  is  quite  ineffective  in  forming  secretin  when 
rubbed  up  with  the  scraped-off  mucous  membrane.  That  secretin 
acts  on  the  pancreatic  cells  in  a  different  way  from  the  secretory 
nerve  fibres  contained  in  the  vagus  is  indicated  by  the  difference  in 
the  characters  of  the  juice  secreted  under  the  influence  of  the  two 
mechanisms.  The  nervous  secre- 
tion is  thick  and  opalescent,  rich 
in  enzymes,  including  trypsin  in 
the  active  form,  and  proteins,  but 
its  alkali  content  is  low.  Like 
other  secretions  excited  through 
nerves,  it  is  inhibited  by  atropine. 
The  chemical  secretion  due  to 
secretin,  is  thin  and  watery,  rich    ^'S-  166.— Rate  of  Secretion  of  Pan- 

11  1-  •  ,  •  1  creatic  Juice.  S  shows  the  variation 
m  alkahes,  poor  m  protems  and  ^^  ^^e  rate  of  secretion  of  the  pan- 
in  enzymes,  and  among  the  latter,  creatic  juice  in  a  dog;  p.  the  varia- 
trypsin  occurs  only  in  the  inactive  ^i^"^  ^  ^^^  percentage  of  solids  in 

form  /^qw^t^h^  ^^^  ^"^^^      ^*  '"'■'^^  ^^  ^^°-  *^^*  ^^^ 

lorm  (bawitscnj.  maxima  of  S  fall  at  the   same  time 

The  pancreatic,  like  the  gastric,         as  the  maxima  of  p.     The  numbers 

juice    is    said    to    vary    as    regards         ^^'^^S  the  horizontal  axis  are  hours 

its  digestive  properi:ies  ^v^th  the  '^'"  '^^  ^^'  °^^^^- 
nature  of  the  food.  On  a  diet  of  bread  the  juice  is  very  poor 
in  fat-splitting  ferment,  while  on  a  diet  of  flesh  it  is  richer,  and 
on  a  diet  of  milk  richest  of  all.  With  bread  the  juice  is  relatively 
rich  in  amylolytic  ferment.  When  we  take  the  quantity  of  the 
juice  as  well  as  its  strength  in  ferments  into  consideration,  it  is 
stated  that  bread  occasions  the  secretion  of  a  juice  with  a  greater 
quantity  of  proteolytic  ferment  than  either  milk  or  meat,  although 
it  is  relatively  dilute  (Fig.  167).  The  vegetable  proteins  require 
more  ferment  to  digest  them  than  proteins  of  animal  origin.  There 
is  no  more  evidence  that  the  adaptation  of  the  pancreatic  juice  to  the 
nature  of  the  food  is  due  to  a  specific  sensibihty  of  the  duodenal 
mucosa  to  the  various  food-stuffs  than  there  is  in  the  case  of  the 
adaptation  of  the  gastric  juice.  If  the  volume  of  the  chyme  and  its 
acidity  are  related  to  the  nature  of  the  food,  then  the  amount  of 
secretin   formed,  and  therefore  the  intensity  of  secretion  in  the 


404 


DIGESTION 


pancreas,  vvnll  be  similarly  related.  The  one  apparently  proved 
example  of  specific  adaptation  of  the  pancreatic  juice  has  not  stood 
the  test  of  a  critical  examination.  It  was  asserted  that  in  dogs  fed 
for  some  days  with  food  containing  lactose  (milk)  the  ferment, 
lactase,  is  present  in  that  secretion,  while  the  pancreatic  juice  of 
dogs  whose  food  is  free  from  lactose  does  not  contain  lactase.  The 
adaptation  of  the  pancreas  to  lactose  was  supposed  to  be  achieved 
through  some  substance  produced  by  the  action  of  lactose  on  the 
I  11  ui  IV  V   1  II  ui  IV  V  vi  vnvmi  iiiii  IV  V  VI      mtestmal   mucous 

membrane,  which 
plays  the  part  of 
a  specific  chemical 
stimulus  to  the 
pancreatic  cells  or 
their  secretory 
nervous  mechan- 
ism, causing  them 
to  form  lactase. 
But  it  has  been 
conclusively  shown 
that  when  dogs 
are  fed  with  lac- 
tose for  weeks  no 
lactase  appears  in 
the  pancreatic 
juice  (Phmmer). 

The  natural  se- 
cretion of  pan- 
creatic juice  is  by 
no  means  so  inter- 
mittent as  that  of 
saliva.  In  the  rab- 
bit the  pancreatic, 
like  the  gastric, 
juice  flows  con- 
tinuously. In  the 
dog  it  begins  al- 
,     J   .        ,  .        .  most   as   soon    as 

food  IS  taken,  rises  m  two  or  three  hours  to  a  maximum  then 
falls  till  the  fifth  or  sixth  hour,  after  which  it  may  mount 'again 
somewhat,  and  then,  gradually  diminishing,  ultimately  stops  (Figs 
166,  167).  During  normal  activity  the  bloodvessels  of  the  gland  are 
dilated.  But  under  experimental  conditions  the  increased  secretion 
caused  by  secretin  is  accompanied  sometimes  by  an  increase  and 
sometimes  by  a  diminution  in  the  blood-flow,  and  secretion  may 
continue  for  some  time  after  complete  cessation  of  the  circulation 


\  d 


l!!!!!!il!!BHB0imiiSi 


aHaBBIIBBBHaHHilHIBlia 
BBBBBBBBBBBBfiBBBBB 

IBBBBBBBBBBBBBBBBBB 


Flesh,  100  grm.  Bread,  250  grm. 


Milk,  600  grm. 


Fig.  167. — Secretion   of   Pancreatic    Juice  with  Different 
Diets  (Pawlow).     The  hours  are  in  roman  numerals. 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DICE  ST  I  VE  GLANDS     405 


while  the  increased  consumption  of  oxygen  which  goes  hand  in  hand 
with  the  increased  secretion  is  also  independent  of  the  blood-supply 
(May,  Barcroft  and  Starling).  This  shows  how  far  the  secretory  pro- 
cess is  from  a  mere  mechanical  filtration,  although  it  does  not  follow 
that,  under  normal  conditions,  a  decreased  blood-flow  ever  does 
accompany  an  increased  secretion.  There  is  one  difference  between 
the  normal  secretion  of  pancreatic  juice  and  of  saliva  which  may  still 
be  mentioned :  the  pressure  of  the  latter  in  the  submaxillary  duct  may, 
as  we  have  seen,  greatly  exceed  the  arterial  blood-pressure,  without 
reabsorption  and  consequent  oedema  of  the  gland  occurring;  but  the 
secretory  pressure  of  the  pancreatic  cells  is  very  low,  not  more  than 
a  tenth  of  that  of  the  salivary  glands. 
(Edema  begins  before  a  manometer  in 
the  duct  shows  a  pressure  of  20  mm. 
of  mercury,  the  secreted  fluid  passing 
very  easily  into  the  lymph  spaces. 

The  mutual  relations  of  the  spleen 
and  pancreas  have  formed  the  subject 
of  numerous  inquiries.  Some  authors 
maintain  that  the  spleen  plays  an  im- 
portant role  in  the  elaboration  of  the 
proteolytic  ferment  of  the  pancreas, 
forming  a  substance  which  we  may  call 
pro-trypsinogen,  since  it  is  supposed  to 
be  carried  in  the  blood  to  the  pancreatic 
cells,  and  changed  by  them  into  trypsin- 
ogen.  There  is  some  evidence  that 
extracts  of  the  spleen  prepared  from  it 
when  congested  during  digestion  exert  a 
favourable  influence  on  the  proteolytic 
power  of  the  pancreas  (Mendel).  And 
there  is  no  doubt  that  the  spleen,  like 
other  organs,  contains  an  intracellular 
enzyme  which  can  aid  in  the  digestion 
of  protein.  The  products  of  the  action 
in  an  acid  medium  of  this  enzyme  are  the  same  as  those  formed  by 
trypsin  in  an  alkahne  medium  (Leathes).  But  this  is  not  enough  to 
prove  that  the  spleen  has  any  special  relation  to  pancreatic  digestion. 

The  Influence  of  Nerves  on  the  Secretion  of  Bile. — Although  bile  is 
secreted  constantly,  it  only  passes  at  intervals  into  the  intestine. 
For  the  liver  in  many  animals,  unlike  every  other  gland  except  the 
kidney,  has  in  connection  with  it  a  reservoir,  the  gall-bladder,  in 
which  its  secretion  accumulates,  and  from  which  it  is  only  expelled 
occasionally.  We  have  therefore  to  distinguish  the  bile-secretion 
from  the  bile-expeUing  mechanism.  To  stud}'  the  rate  of  secreting 
of  bile  (Fig.  168),  a  fistula  of  the  gall-bladder  can  be  estabUshed. 


Fig.  168. — Rate  of  Secretion  of 
Bile.  S  shows  how  the  rate  of 
secretion  of  bile  falls  in  a  dog 
when  a  biliary  fistula  is  first 
made,  and  the  bile  thus  pre- 
vented from  entering  the  intes- 
tine ;  P  shows  the  fall  of  the  per- 
centage of  soUds.  The  numbers 
along  the  horizontal  axis  are 
quarters  of  an  hour  since  bile 
began  to  escape  through  the 
fistula.  The  numbers  along 
the  vertical  axis  refer  only  to 
curve  S,  and  represent  the  rate 
of  secretion  in  arbitrary  units. 


4o6  DIGESTION 

But  to  learn  the  function  of  bile  in  digestion  it  is  more  important 
to  know  when  and  at  what  rate  it  enters  the  intestine.  For  this 
purpose  a  fistula  is  made  by  cutting  the  natural  orifice  of  the  common 
bile-duct  with  a  piece  of  the  surrounding  mucous  membrane  out  of 
the  intestine  and  transplanting  it  upon  the  serous  coat,  where  it  is 
sutured.  The  loop  of  intestine,  with  the  orifice  of  the  duct  facing 
outwards,  is  then  stitched  into  the  abdominal  wound,  where  it  is 
allowed  to  heal.  Of  course,  since  a  circulation  of  the  bile-acids 
takes  place — i.e.,  an  absorption  from  and  re-excretion  into  the 
intestine — the  formation  of  that  juice  cannot  proceed  upon  abso- 
lutely normal  Hnes  when  the  bile  no  longer  enters  the  duodenum. 
The  only  condition  under  which  fistula  bile  could  have  the  same 
composition  as  normal  bile  would  be  that  in  which  as  great  an 
amount  of  bile-acids  is  introduced  into  the  gut  as  escapes  through 
the  fistula.  A  circulation  of  a  smaller  proportion  of  the  bile-pig- 
ments is  also  probable.  A  circulation  of  the  biliary  cholesterin  is 
denied  by  some  observers  (Stadelmann)  but  affirmed  by  others.  It 
is  certain  that  cholesterin  is  of  importance  in  the  body,  and  if  the 
supply  of  sterins  (p.  561)  in  the  food  is  insufficient  it  is  to  be  sup- 
posed that  some  of  the  bihary  cholesterin  would  be  used  over  again. 

Of  the  direct  influence  of  nerves,  either  on  the  secretion  of  bile  or  on 
its  expulsion,  we  have  scarcely  any  knowledge,  scarcely  even  any  guess 
which  is  worth  mentioning  here.  It  is  true  the  secretion  of  bile  may 
be  distinctly  affected  by  the  section  and  stimulation  of  nerves  which 
control  the  blood-supply  of  the  stomach,  intestines,  and  spleen,  for  the 
quantity  of  blood  passing  by  the  portal  vein  to  the  liver  depends  upon 
the  quantity  passing  through  these  organs,  and  the  rate  of  secretion  is 
diminished  when  the  blood-supply  is  greatly  lessened.  In  this  way 
stimulation  of  the  medulla  oblongata,  the  spinal  cord,  or  the  splanchnic 
nerves  stops  or  slows  the  secretion  of  bile  by  constricting  the  abdominal 
vessels ;  and  the  same  effect  can  be  reflexly  produced  by  the  excitation 
of  afferent  nerves. 

The  right  splanchnic  nerve  contains  inhibitory  with  some  motor 
fibres,  and  the  vagi  (especially  the  left)  contain  motor  fibres  for  the 
gall-bladder.  Probably  its  contraction  takes  place  naturally  in 
response  to  reflex  impulses  from  the  mucous  membrane  of  the  duo- 
denum, for  the  application  of  dilute  acid  to  the  mouth  of  the  bile- 
duct  causes  a  sudden  flow  of  bile,*  and  the  acid  contents  of  the 
stomach,  when  projected  through  the  pylorus  into  the  intestine, 
have  a  similar  effect.  But,  in  addition,  as  we  have  seen,  the  secretin 
formed  will  cause  an  increase  in  the  rate  of  secretion  of  the  bile.  In 
studying  the  effect  of  secretin  it  is  necessary  to  obtain  it  free  from 
bile-salts,  since  these  cause  of  themselves  an  increased  secretion  of 
bile.  When  this  is  done  by  dissolving  out  with  alcohol  any  bile-salts 
which  may  be  present  in  the  extract  of  intestinal  mucous  membrane, 

*  This  result  seems  to  be  difficult  to  realize  experimentally.  Bainbridge 
and  Dale  could  not  elicit  reflex  contraction  of  the  gall-bladder  (in  anaesthetized 
animals)  in  this  way. 


INFL UENCE  OF  NER  VO US  S  YSTEM  ON  DIGESTI VE  GLA NDS     407 

a  solution  of  the  residue  containing  the  secretin  still  evokes  a  rapid 
secretion  of  bile.  The  fact  that  the  same  hormone  excites  the 
formation  both  of  pancreatic  juice  and  bile  is  obviously  related  to 
that  common  action  of  the  two  juices  in  digestion  on  which  we  have 
already  dwelt. 

When  food  passes  into  the  stomach,  there  is  at  once  a  sharp  rise  in 
the  rate  of  secretion  of  bile.  A  maximum  is  reached  from  the  fourth 
to  the  eighth  hour — that  is,  while  the  food  is  in  the  intestine.  There 
is  then  a  fall,  succeeded  by  a  second  smaller  rise  about  the  fifteenth 
or  sixteenth  hour,  from  which  the  secretion  gradually  decUnes  to  its 
minimum.  Upon  the  whole,  the  curves  of  secretion  of  pancreatic 
juice  and  bile  show  a  fairly  close  correspondence,  except  that  the 
latter  is  more  nearh'  continuous.  But  when  we  compare  the  curves 
representing  the  rate  at  which  the  bile  actually  enters  the  intestine 
with  the  curve  of  pancreatic  secre- 
tion (Fig.  160),  we  are  struck  by 
their  almost  absolute  parallelism. 
This  lends  additional  support  to 
the  conclusion  deduced  from  their 
chemical  and  physical  properties, 
that  in  digestion  they  are  partners 
in  a  common  work. 

While    the    rate    at    which    bile 
passes  into  the  intestine  seems  to  be 

influenced  by  digestion  much  in  the  Fig^ieg.-Pancreatic  juice  and  BUe 

-'        °                                       .  (Pawlow).    The  upper  curves  repre- 

same  way  as  the  rate  of  pancreatic  sent  the  hourly  rate  of  pancreatic 

secretion,  the  details  are  as  yet  less  secretion,  and  the  lower  the  rate  at 

exactly      known.        In     the      fasting  which  the  bile  enters  the  intestine; 

\         ,  .,          .         .1            .      •t■,r^  a,  a  ,  milk  diet;  &,  6  ,  meat;  c,  c'. 

animal  no  bile  enters  the  gut.    W  hen  bread.     Only  the  general  form  of 

food  is  taken,  the   flow  begins  after  the  curves  is  to  be  compared.     The 

a  definite  interval,  which  varies  for       ^^^^^  °^  ^^^  ordinates  of  the  various 

,,  ,.„  ,1-1  f     f       T  A  curves  was  not  the  same, 

the    dmerent    kinds    of   food.      As 

long   as  digestion  lasts  bile  continues   to   escape,    but   both  the 

quantity  and  quality  depend  upon  the  nature  of  the  food.     Water, 

raw  egg-white,  and  starch  paste,  whether  given  by  the  mouth  or 

introduced  directly  into  the  stomach  of  a  dog,  cause  no  flow  of  bile. 

But  fat,  the  extractives  of  meat,  and  the  pro  lucts  of  digestion  of 

egg-white  produce  a  copious  discharge.     This  discharge  may  be 

determined  by  the  relatively  large  amount  of  acid  chyme  passed 

through  the  pylorus  when  proteins  are  digested  in  the  stomach  and 

the  stimulus  to  the  formation  of  secretin  occasioned  by  the  presence 

of  this  chyme  or  of  fatty  material  in  the  duodenum.    In  the  case  of 

fat  a  further  favourable  influence  on  the  secretion  of  bile  is  the 

absorption  of  bile-salts  which  accompanies  the  absorption  of  the 

fatty  acids  and  soaps  produced  in  fat  digestion.     Bile-salts  stimulate 

the  secretion  of  bile,  including  bile-salts  thems  Ives.     An  increased 


4o8  DIGESTION 

flow  of  bile-salts  into  the  intestine  accelerates  the  splitting  of  fats  by 
the  pancreatic  juice,  and  therefore  the  absorption  of  bile- salts  acting 
as  solvents  for,  or  chemically  united  to,  the  fatty  acids  and  soaps. 
A  circle  analogous  to  the  '  vicious  circle  '  of  the  logicians,  but  con- 
stituting a  physiological  adaptation  of  most  potent  virtue  in  the 
digestion  of  fats,  is  thus  estabhshed.  Not  only  is  the  quantity  of 
bile  poured  into  the  intestine  increased  on  a  diet  rich  in  fat,  but  it 
is  said  that  a  given  amount  of  it  aids  the  fat-sphtting  action  of  the 
pancreatic  juice  more  powerfully  than  if  the  diet  were  poor  in  fat. 
This  may  depend  upon  an  increase  in  the  concentration  of  the  bile- 
salts  in  bile  secreted  when  a  large  amount  of  fat  is  ingested.  But  it 
is  well  to  recognize  that  we  do  not  at  present  know  with  any  great 
exactness  the  mechanism  by  which  the  rate  of  secretion  and  ex- 
pulsion of  bile  and  the  properties  of  that  juice  are  influenced  by 
digestion.  It  has  been  conjectured  that  the  first  abrupt  rise  may  be 
started  by  reflex  nervous  action,  and  that  later  on  secretin  and,  in  the 
case  of  fat  digestion,  bile-salts  may  directly  excite  the  hepatic  cells. 

The  pressure  under  which  the  bile  is  secreted  is  higher  than  the 
pressure  of  the  portal  blood,  and  therefore  the  hver  ranges  itself  with 
the  high-pressure  salivary  glands  rather  than  with  the  low-pressure 
pancreas.  But  although  the  biliary  pressure  is  high  relatively  to 
that  of  the  blood  with  which  the  secreting  cells  are  supplied,  it  is 
absolutely  low,  the  maximum  being  no  more  than  25  mm.  of  mer- 
cury.* This  is  a  point  of  practical  importance,  for  a  comparatively 
sHght  obstruction  to  the  outflow,  even  such  as  is  offered  by  a  con- 
gested or  inflamed  condition  of  the  duodenal  wall  about  the  mouth 
of  the  duct,  may  be  sufficient  to  cause  reabsorption  of  the  bile 
through  the  lymphatics,  and  consequent  jaundice.  Of  course, 
complete  plugging  of  the  duct  by  a  biliary  calculus  is  a  much  more 
formidable  barrier,  and  inevitably  leads  to  jaundice,  just  as  ligature 
of  a  sahvary  duct,  in  spite  of  the  great  secretory  pressure,  inevitably 
causes  oedema  of  the  gland. 

The  Influence  of  Nerves  on  the  Secretion  of  Intestinal  Juice. — As 
to  the  influence  of  nerves  on  the  secretion  of  the  succus  entericus,  our 
knowledge  is  almost  limited  to  a  single  experiment,  and  that  an  in- 
conclusive one.  Moreau  placed  four  hgatures  on  a  portion  of  the 
small  intestine,  so  as  to  form  three  compartments  separated  from 
each  other  and  from  the  rest  of  the  gut.  The  mesenteric  nerves 
going  to  the  middle  loop  were  divided,  and  the  intestine  returned  to 
the  abdomen.  After  some  time  a  watery  secretion  was  found  in  the 
middle  compartment,  httle  or  none  in  the  others.  This  is  a  true 
'  paralytic '  secretion,  and  not  a  mere  transudation  depending 
simply  on  the  vascular  dilatation  caused  by  section  of  the  vaso- 

*  In  the  (log,  cat,  and  monkey  the  average  maximum  pressure  at  which 
as  much  bile  is  secreted  as  is  taken  up  from  the  bile-paths  by  the  portal 
lymphatics  is  about  300  mm.  of  bile.  The  highest  pressure  recorded  was 
373  mm.  of  bile  in  a  cat  (Herring  and  Simpson). 


INFLUENCE  OF  NERVOUS  SYSTEM  ON  DIGESTIVE  GLANDS     409 

constrictor  nerves,  for  it  has  the  same  composition  and  digestive 
action  as  normal  succus  entcricus  obtained  from  a  fistula.  The 
secretion  begins  about  four  hours  after  section  of  the  nerves,  goes  on 
increasing  for  about  twelve  hours,  and  then  rapidly  diminishes,  so 
that  after  about  two  days  the  middle  loop,  as  well  as  the  other 
two,  will  be  found  empty.  The  interpretation  usually  put  upon  the 
experiment  is  that  nerves  which  normally  inhibit  the  local  secre- 
tory mechanism  have  been  divided.  But  there  is  no  real  proof  of 
the  existence  of  such  nerves. 

The  same  adaptation  is  seen  in  the  secretion  of  the  succus  entericus 
as  in  the  secretion  of  the  other  digestive  juices,  and  the  adaptation 
is  naturally  most  striking  in  regard  to  those  points  in  which  the 
intestfnal  juice  is  peculiar.  While  mechanical  stimulation  of  the 
stomach  is  ineffective  as  regards  the  secretion  of  gastric  juice, 
mechanical  stimulation  of  the  intestine,  as  by  the  contact  of  a 
cannula,  produces  a  free  flow  of  succus  entericus.  The  reaction  is  a 
localized  one,  the  secretion  only  taking  place  from  the  portion  of  the 
mucous  membrane  stimulated.  This  fact  acquires  significance  when 
we  reflect  that  the  food  moves  very  slowly  in  the  intestine,  and  a 
secretion  could  be  of  use  only  at  the  points  where  the  food  happened 
to  be.  The  juice  secreted  in  response  to  mechanical  stimulation  is 
poor  in  enterokinase.  But  if  a  Httle  pancreatic  juice  be  put  into  the 
intestine,  and  left  there  for  some  time,  the  juice  afterwards  secreted 
is  rich  in  enterokinase. 

Summary. — Here  let  us  sum  up  the  most  important  points  relat- 
ing to  the  secretion  of  the  digestive  juices.  They  are  all  formed  by 
the  activity  of  gland-cells  originally  derived  from  the  epithelial  lining 
of  the  alimentary  canal.  The  organic  constituents  or  their  precursors 
(including  the  mother-substances  of  the  ferments)  are  prepared  in  the 
intervals  of  rest — absolute  in  some  glands,  relative  in  others — and 
stored  up  in  the  form  of  granules,  which  during  activity  are  moved 
towards  the  lumen  of  the  gland  tubules,  and  there  discharged. 

The  nerves  of  the  salivary  glands  are,  as  regards  their  origin,  [a) 
cerebral,  (b)  sympathetic ;  the  former  group  is  vaso-dilator,  the  latter 
(usually)  vaso-constrictor ;  both  are  secretory.  Secretion  of  saliva 
depends  strictly  on  the  nervous  system.  That  neives  influence  the 
gastric  and  pancreatic  secretions  is  also  made  out.  The  psychical  secre- 
tion is  of  greater  importance  for  the  saliva  and  gastric  juice  than  for 
the  pancreatic  juice.  The  direct  action  of  secretin  (produced  in  the 
intestinal  mucous  membrane  by  the  influence  of  the  chyme)  is  the  most 
characteristic  factor  in  pancreatic  secretion.  As  regards  the  intestinal 
glands  and  the  liver,  it  has  not  been  proved  that  their  secretive  activity 
is  under  the  control  of  the  nervous  system,  except  in  so  far  as  the  latter 
may  indirectly  govern  it  through  the  blood-supply,  although  various 
circumstances  suggest  the  probability  of  a  more  direct  action.  All  the 
digestive  juices  show  a  certain  adaptation  to  the  nature  of  the  food, 


4IO  DIGESTION 

although  it  has  not  been  demonstrated  that  this  is  due  to  a  specific  sensi- 
bility of  the  mucous  membranes  for  each  kind  of  food-stuff.  The 
action  of  one  juice  on  the  secretion  of  another  is  also  of  great  significance. 
Thus,  the  water  of  the  saliva  directly  excites  a  flow  of  gastric  juice  when 
it  reaches  the  stomach ;  the  acid  of  the  gastric  juice  excites  a  flow  of 
pancreatic  juice  when  it  reaches  the  duodenum ;  and  the  pancreatic 
juice  excites  the  intestinal  mucous  membrane  to  the  production  of 
enterokinase,  the  most  characteristic  constituent  of  the  succus  entericus. 
In  all  the  glands  the  blood-flow  is  increased  during  activity ;  in  some 
{salivary  glands)  this  is  known  to  be  caused  through  vaso-motor  nerves. 
In  the  salivary  glands  electro-motive  changes  accompany  the  active 
state,  and  more  heat  is  produced.  Both  in  the  salivary  glands  and  the 
pancreas  it  has  been  shown  that  much  more  carbon  dioxide  is  given  off, 
and  much  more  oxygen  used  up,  during  secretion  than  during  rest.  In 
the  other  glands  we  may  assume  that  the  same  occurs.  This  is  one 
proof  that  work  is  done  in  the  separation  or  manufacture  of  the  con- 
stituents of  the  various  secretions. 

Section  VI. — Survey  of  Digestion  as  a  Whole. 

Having  discussed  in  detail  the  separate  action  of  the  digestive 
secretions,  it  is  now  time  to  consider  the  act  of  digestion  as  a  whole, 
the  various  stages  in  which  are  co-ordinated  for  a  common  end. 
The  solid  food  is  more  or  less  broken  up  in  the  mouth  and  mixed 
with  the  saliva,  which  its  presence  causes  to  be  secreted  in  consider- 
able quantity.  Liquids  and  small  solid  morsels  are  shot  down  the 
open  gullet  without  contraction  of  the  constrictors  of  the  pharynx, 
and  reach  the  lower  portion  of  the  oesophagus  in  a  comparatively 
short  time  (y\y  second) ;  while  a  good-sized  bolus  is  grasped  by  the 
constrictors,  then  by  the  oesophageal  walls,  and  passed  along  by  a 
more  deliberate  peristaltic  contraction. 

Chemical  digestion  in  man  be^gins  already  in  the  mouth,  a  part  of 
the  starch  being  there  converted  into  dextrins  and  sugar  (maltose), 
as  has  been  shown  by  examining  a  mass  of  food  containing  starch 
just  as  it  is  ready  for  swallowing  (p.  450).  This  process  is  no  doubt 
continued  during  the  passage  of  the  food  along  the  oesophagus. 

The  first  morsels  of  a  meal  which  reach  the  stomach  find  it  free 
from  gastric  juice,  or  nearly  so.  They  are  alkaline  from  the  ad- 
mixture of  saliva ;  and  the  juice  which  is  now  beginning  to  be  secreted, 
in  response  to  the  psychical  excitement,  and  refiexly  through  the 
presence  of  the  food  and  the  water  of  the  saliva  in  the  stomach,  is  for 
a  time  neutralized,  and  amylolytic  digestion  still  permitted  to  go  on. 
For  20  to  40  minutes  after  digestion  has  begun  there  is  no  free 
hydrochloric  acid  in  the  stomach,  although  some  is  combined  with 
proteins,  and  during  this  period  the  ptyalin  of  the  swallowed  saliva 
will  be  able  to  act  even  better  than  in  the  mouth,  being  favoured  by 


SURVEY  OF  DIGESTION  AS  A   WHOLE  411 

a  weakly  acid  reaction.  Indeed,  for  a  time,  as  the  meal  goes  on,  the 
successive  portions  of  food  which  arrive  in  the  stomach  will  find  the 
conditions  more  and  more  favourable  for  amylolytic  digestion.  But 
as  the  acidity  continues  to  increase,  the  activity  of  the  ptyalin  will 
first  be  lessened,  and  ultimately  abolished;  and,  upon  the  whole,  a 
considerable  proportion  of  the  starches  must  usually  escape  com- 
plete conversion  into  sugar  until  they  are  acted  upon  by  the  pan- 
creatic juice.  This  is  particularly  the  case  with  unboiled  starch,  as 
contained  in  vegetables  which  are  eaten  raw;  and,  indeed,  we  know 
that  sometimes  a  certain  amount  of  starch  may  escape  even  pan- 
creatic digestion,  and  appear  in  the  faeces.  Meanwhile,  pepsin  and 
hydrochloric  acid  are  being  poured  forth;  the  latter  is  entering  into 
combination  with  the  proteins  of  the  food ;  and  before  the  end  of  an 
ordinary  meal  peptic  digestion  is  in  full  swing.  The  movements  of 
the  pyloric  end  of  the  stomach  increase,  and  eddies  are  set  up  in  its 
contents,  which  carry  the  morsels  of  food  with  them,  and  throw  them 
against  its  walls.  In  this  way  not  only  are  the  contents  thoroughly 
mixed,  and  fresh  portions  of  food  constantly  brought  into  contact 
with  the  gastric  juice  secreted  mainly  in  the  more  passive  cardiac 
end,  but  a  certain  amount  of  mechanical  disintegration  is  brought 
about.  This  is  aided  by  the  digestion  of  the  gelatin-yielding  con- 
nective tissue  which  holds  together  the  fibres  of  muscle  and  the  cells 
of  fat,  and  the  digestible  structures  in  vegetable  tissue  which  enclose 
starch  granules.  Such  nucleo-proteins  as  come  into  contact  with  the 
gastric  juice  will  be  split  up  and  the  proteins  digested  to  peptone. 
The  globin  of  the  blood  pigment  will  undergo  the  same  change,  while 
the  haematin  is  not  much  affected.  If  milk  has  formed  a  portion  of 
the  meal,  the  caseinogen  will  have  been  curdled  soon  after  its 
entrance  into  the  stomach,  bv  the  action  of  the  rennet  ferment  alone 
(see  p.  349)  when  the  milk  has  been  taken  at  the  beginning  of 
digestion  before  the  gastric  contents  have  become  distinctly  acid,  by 
the  acid  and  ferment  together  when  it  has  been  taken  later.  The 
caseinogen  and  other  proteins  of  milk,  like  the  myosinogen  and  other 
proteins  of  meat,  and  the  globulins,  albumins,  and  other  proteins  of 
bread  and  of  vegetable  food  in  general,  are  acted  upon  by  the  pepsin 
and  hydrochloric  acid,  yielding  ultimately  peptones;  while  variable 
quantities  of  these  proteins  and  of  the  acid-albumin  and  proteoses 
derived  from  them  may  escape  this  final  change,  and  pass  on  as  such 
into  the  duodenum.  In  the  dog,  indeed,  a  very  large  proportion  of 
a  meal  of  flesh  has  been  found  to  be  digested  to  the  peptone  stage 
while  still  in  the  stomach,  leaving  for  the  juices  that  act  on  it  in  the 
intestine  only  its  further  hydrolysis  to  amino-acids,  etc.  But  we 
may  safely  assume  that,  in  the  case  of  a  man  living  on  an  ordinary 
mixed  diet,  a  good  deal  of  the  food  proteins  passes  through  the 
pylorus  chemically  unchanged,  or  having  undergone  only  the  first 
steps  of  hydration.     For,  even  a  few  minutes  after  food  has  been 


412  DIGESTION 

swallowed,  especially  liquid  food  or  water,  the  pyloric  sphincter 
may  relax  and  allow  the  stomach  to  propel  a  portion  of  its  contents 
into  the  intestine ;  and  such  relaxations  occur  at  intervals  as  diges- 
tion goes  on,  although  it  is  not  for  several  hours  (three  to  five)  that 
the  greater  portion  of  the  food  reaches  the  duodenum.  During  this 
period  the  acidity  has  at  first  been  constantly  increasing,  although 
for  a  time  the  hydrochloric  acid  has  combined,  as  it  is  formed,  with 
the  proteins  of  the  food.  Then  comes  a  stage  where  the  hydrochloric 
acid  has  so  much  increased  that,  after  combining  with  all  the  proteins, 
some  of  it  remains  over  as  free  acid.  After  a  time  the  total  acidity 
begins  to  fall,  the  partially  digested  proteins  continually  passing  on 
through  the  pylorus,  while  a  considerable  proportion  is  so  fully 
digested  as  to  be  absorbed  by  the  gastric  mucous  membrane  itself. 
Thus,  in  one  experiment  on  the  digestion  of  meat  in  a  dog,  it  was 
found  that  30  per  cent,  was  absorbed  in  the  stomach,  while  40  per 
cent,  passed  through  the  pylorus  as  peptone,  over  20  per  cent,  as 
undissolved  or  soluble  protein  (acid- albumin),  and  a  little  more  than 
8  per  cent,  as  proteose  (Tobler).  The  large  proportion  of  peptone 
is  noteworthy,  as  indicating  some  kind  of  selective  passage  of  the 
different  digestive  products  from  the  stomach  into  the  duodenum. 
For  the  gastric  contents  contain  plenty  of  proteose,  although  only 
traces  of  peptone.  The  total '  titratable  acidity  '  goes  on  diminishing 
till  the  third  or  fourth  hour,  the  proportion  of  free  to  combined  acid 
continuing,  nevertheless,  to  rise,  since  nearly  all  that  is  now  secreted 
remains  free.  In  addition  to  a  certain  amount  of  protein,  small 
quantities  of  soluble  and  easily  diffusible  substances,  like  sugars  and 
some  of  the  organic  crystalHne  constituents  of  meat — e.g.,  kreatin — 
may  also  be  absorbed  into  the  blood  by  the  gastric  mucous  membrane. 
The  substances  which  reach  the  duodenum  are — (i)  The  greater 
part  of  the  fats.  The  partial  digestion  in  the  stomach  of  the  enve- 
lopes and  protoplasm  of  the  cells  of  adipose  tissue,  and  of  the  protein 
which  keeps  the  fat  of  milk  in  emulsion,  prepares  the  fats  which  are 
not  split  up  by  the  gastric  juice  for  what  is  to  follow  in  the  intestine. 
(2)  All  the  proteins  which  have  not  been  carried  to  the  stage  of 
peptone,  and  much  peptone.  (3)  All  the  starch  and  dextrins — and 
glycogen,  if  any  be  present — which  have  not  been  converted  into 
sugars,  and  probably  a  portion  of  the  sugars.  (4)  Nucleins,  hsematm, 
cellulose,  and  other  substances  not  digestible,  or  digestible  only  with 
difficulty,  in  gastric  juice.  (5)  The  constituents  of  the  gastric  juice 
itself,  including  pepsin.  Most  of  the  pepsin  is  soon  destroyed  in  the 
unfavourable  environment  of  the  intestinal  contents.  But  it  has 
been  shown  that  a  certain  amount  of  active  pepsin  may  be  present 
for  a  time  in  the  intestine,  even  in  the  free  condition,  and  still  more 
when  enclosed  in  the  interior  of  masses  of  protein  which  protect  it, 
and  which  still  continue  to  be  digested  by  it.  This  is  particularly 
true  of  certain  materials,  like  elastin  and  connective  tissue,  which  are 


SURVEY  OF  DIGESTION  AS  A    WHOLE  413 

more  readily  hydrolysed  by  pepsin  than  by  trypsin.     The  ptyahn 
of  the  sahva  has  been  already  destroyed  in  the  stomach. 

It  must  be  remembered  that  all  this  time,  even  from  the  beginnifig 
of  digestion,  a  certain  amount  of  pancreatic  juice  has  been  finding 
its  way  into  the  duodenum  in  response  first  perhaps  to  the  psychical 
excitation,  and  later  to  that  action  of  the  acid  chyme  on  the  in- 
testinal mucous  membrane  which  has  been  described.  In  the 
duodenum  its  trypsinogen  is  becoming  activated  to  trypsin  by  the 
enterokinase  of  the  intestinal  juice.  The  secretion  of  bile,  too,  has 
quickened  its  pace,  the  gall-bladder  is  getting  more  and  more  full  as 
the  meal  proceeds  and  gastric  digestion  begins,  and  some  of  the  bile 
may  very  soon  escape  into  the  intestine.  The  pylorus  opens  occa- 
sionally for  a  moment  whenever  the  small  portions  of  chyme  which 
at  this  stage  are  beginning  to  pass  through  have  been  sufficiently 
neutrahzed  by  the  pancreatic  juice  and  bile,  although  it  is  not 
necessary  that  the  reaction  should  become  actually  neutral.  When 
the  acid  chyme,  a  greyish  liquid,  turbid  with  the  debris  of  animal  and 
vegetable  tissues — with  muscular  fibres,  fat  globules,  starch  granules, 
and  dotted  ducts — gushes  through  the  pylorus  and  strikes  the 
duodenal  wall,  the  muscular  fibres  of  the  gall-bladder  contract,  and 
sudden  rushes  of  bile  take  place  from  the  common  duct.  By-and-by, 
as  bile  and  pancreatic  juice  continue  to  be  poured  out,  the  reaction 
in  the  duodenum,  as  tested  by  litmus,  becomes  less  acid  and  even 
weakly  alkaline  for  a  time.  But  it  soon  becomes  acid  again,  and  the 
acidity  at  first  increases  as  the  food  passes  down  the  gut.  In  the 
lower  portion  of  the  small  intestine  the  acidity  diminishes,  and  the 
contents  may  be  neutral  or  actually  alkaline  for  some  distance  above 
the  ileo-cascal  valve.  To  phenolphthalein  the  reaction  is  acid 
throughout  the  whole  intestine.  But  methyl  orange  shows  an 
alkaline  reaction,  all  the  way  from  the  lower  end  of  the  duodenum 
to  the  caecum  (Moore  and  Rockwood).  In  the  upper  part  of  the 
duodenum  the  reaction  with  this  indicator  is  sometimes  found  acid, 
but  sometimes  neutral  or  alkaline.  All  this  refers  to  the  conditions 
during  full  digestion  (3  or  4  to  8  or  9  hours  after  the  taking  of  food). 
When  digestion  is  over  {20  to  24  hours  after  a  meal)  the  reaction 
becomes  acid  to  methyl  orange,  litmus,  and  phenolphthalein  through- 
out the  whole  intestine.*  But  it  must  be  remembered  that  the 
differences  in  true  reaction  at  different  stages  of  intestinal  digestion 
and  at  different  levels  of  the  gut  are  always  slight.  There  is  never 
a  great  preponderance  either  of  hydroxyl  or  of  hydrogen  ions  be- 
tween the  point  at  which  the  pancreatic  juice  and  bile  are  mingled 
with  the  gastric  chyme  and  the  lower  part  of  the  ileum. 

•  In  iS  dogs  fed  with  meat  20  to  24  hours  before  death  this  was  found 
to  be  the  case.  In  4  of  the  dogs  the  gastric  contents  were  almost  neutral 
to  litmus  and  methyl  orange,  but  sliglitly  alkaline  to  phenolphthalein;  in 
the  rest  acid  to  all  three  indicators. 


414  DIGESTION 

Reaction  of  Intestinal  Contents. — A  consideration  of  the  properties  of 
the  indicators  mentioned  enables  us  to  interpret  in  some  measure  these 
results,  which  at  first  sight  appear  so  confusing.  Methyl  orange,  the 
most  stable  of  the  series,  is  not  affected  by  weak  organic  acids,  but  reacts 
acid  to  inorganic,  and  the  stronger  organic  acids  like  lactic,  acetic  and 
butyric  acids,  and  alkaline  to  salts  of  the  weaker  acids,  such  as  sodium 
carbonate  and  bicarbonate.  Phenolphthalein  is  very  sensitive  to  acids, 
even  to  weak  organic  acids  such  as  the  fatty  acids  derived  from  the  fat 
of  meat,  and  to  carbonic  acid.  Litmus  is  intermediate  between  methyl 
orange  and  phenolphthalein.  The  chyme,  as  it  passes  through  the 
pylorus,  contains  free  hydrochloric  acid.  It  mingles  immediately  with 
the  alkaline  contents  of  the  duodenum.  If  these  contain  a  sufficient 
quantity  of  bases  to  combine  with  the  whole  of  the  acids  which  would 
affect  methyl  orange,  that  indicator  will  show  a  neutral  or  alkaline  re- 
action. Phenolphthalein  may  at  the  same  time  react  acid  on  account  of 
the  presence  of  weaker  acids,  including  carbonic  acid,  either  ongmally 
dissolved  in  the  intestinal  fluid  or  liberated  by  the  action  of  the  acids 
of  the  chyme  on  the  carbonates.  If  there  is  not  enough  alkali  to  combine 
with  the  whole  of  the  stronger  acids,  the  reaction  will  be  at  first  acid  to  all 
the  indicators,  but  may  soon  become  alkaline  to  methyl  orange  ov  even 
to  litmus,  as  pancreatic  juice  and  bile  continue  to  enter  the  duodenum. 
As  the  food  progresses  along  the  intestine  a  certain  amount  of  lactic 
acid  is  produced  by  the  action  of  micro-organisms  on  the  carbo- 
hydrates. The  alkalies  of  the  intestinal  secretions  are  being  continually 
used  up,  both  to  neutralize  this  acid,  and  to  form  soaps  with  the  fatty 
acids  set  free  from  the  fats  by  the  steapsin  and  the  fat-splitting  bacteria. 
The  point  may  easily  be  reached,  and  as  a  rule  is  reached,  at  which 
enough  of  the  weak  acids  or  of  acid  salts  is  present  to  give  an  acid 
reaction  with  phenolphthalein  or  litmus,  while  the  reaction  is  still 
alkaline  to  methyl  orange.  By  the  time  the  food  has  arrived  at  the 
lower  end  of  the  small  intestine  the  greater  part  of  the  fat-splitting 
may  be  supposed  to  be  over,  and  the  greater  part  of  the  fatty  acids 
absorbed.  The  acids  that  remain  may  be  easily  neutralized  by  the 
alkaline  succus  entericais,  reinforced  by  the  alkalies,  especially  am- 
monia, produced  by  the  ordinary  putrefactive  bacteria  from  proteins; 
and  the  reaction,  previously  alkaline  to  methyl  orange  only,  may  thus 
become  alkaline  to  litmus  as  well.  Dissolved  carbonic  acid  will  still 
account  for  the  acid  reaction  to  phenolphthalein.  Towards  the  end  of 
intestinal  digestion  the  discharge  of  pancreatic  juice,  bile  and  succus 
entericus  having  almost  or  entirely  ceased,  the  acid-forming  bacteria 
appear  again  to  get  the  upper  hand;  and  since  the  reaction  is  acid  to 
methyl  orange  as  well  as  to  the  other  indicators,  we  must  assume  that 
strong  organic  acids,  like  lactic  acid,  are  present.  Very  early  in  the 
meal  the  inflow  of  alkaline  pancreatic  juice,  and  perhaps  of  succus 
entericus,  into  the  intestine  begins ;  and  for  a  considerable  time  this  is 
not  counteracted  by  the  escape  of  any  large  quantity  of  acid  chyme 
through  the  pylorus.  We  must  accordingly  suppose  that  the  con- 
ditions for  the  establishment  of  an  alkaline  reaction  of  the  intestinal 
contents  are  unfavourable  at  the  end  of  intestinal  digestion,  and 
favourable  at  the  beginning  of  gastric  digestion. 

This  question  of  reaction  has  significance  in  two  ways:  in  the  first 
place  the  reaction  affects  the  activity  of  this  or  that  ferment  on 
the  food  substances;  and,  secondly,  it  determines  whether  a  given 
ferment  shall  be  destroyed  or  not  by  another  ferment  or  by  the 
alkalinity  or  acidity  of  the  medium.     Thus  pepsin  can  be  destroyed 


SURVEY  OF  DIGESTION  AS  A    WHOLE  415 

by  the  alkali  of  the  pancreatic  juice,  entero kinase  and  trypsin  by 
the  hydrochloric  acid  of  the  gastric  juice,  trypsinogen  by  the  pepsin 
and  hydrochloric  acid.  Trypsin  has  no  destructive  effect  on  entero- 
kinase  or  trypsinogen  (Mellanby). 

Trypsin,  like  pepsin,  performs  its  work  in  part  in  an  acid  medium ; 
and  although  the  cause  of  the  acidity  and  the  character  of  the 
medium  are  far  from  being  the  same  as  in  the  gastric  juice,  it  is 
obviously  an  advantage  that  the  chief  proteolytic  ferment  should 
be  able  to  act  upon  the  proteins  in  all  parts  of  the  intestine  and 
at  every  stage  of  intestinal  digestion  whether  the  reaction  is  acid 
or  alkaline.  The  proteins  of  the  chyme  are  all  carried  by  the 
trypsin  to  the  stage  of  peptone,  and  the  peptone,  even  in 
perfectly  normal  digestion,  is  further  split  up  into  amino-  and 
diamino-acids  by  the  trypsin  and  by  the  erepsin  of  the  succus 
entericus. 

In  the  lower  portions  of  the  small  intestine  bacteria  of  various 
kinds  are  present  and  active;  and  it  is  not  unlikely  that  even 
throughout  its  whole  length  a  certain  range  of  action  is  permitted 
to  them,  checked  by  the  acidity  of  the  chyme,  though  scarcely  by 
the  feeble  antiseptic  properties  of  the  bile. 

The  lower  end  of  the  small  intestine  is  not  cut  off  by  any  bacteria- 
proof  barrier  from  the  large  intestine,  in  which  putrefaction  is  con- 
stantly going  on.  It  has  been  actually  shown  that  small  particles, 
such  as  lycopodium  spores,  suspended  in  water,  soon  reach  the 
stomach  when  injected  into  the  rectum.  So  that  micro-organisms, 
aided  by  the  anti peristalsis  of  the  colon,  may  be  able  to  work  their 
way  above  the  ileo-colic  sphincter  and  valve,  even  against  the 
downward  peristaltic  movement  of  the  small  intestine.  But  even  if 
this  were  not  the  case,  a  few  bacteria  or  their  spores,  passing  through 
the  stomach  with  the  food,  would  be  enough  to  set  up  extensive 
changes  as  soon  as  they  reached  a  part  of  the  ahmentary  canal 
where  the  conditions  were  favourable  to  their  development.  In- 
deed, from  the  time  when  the  first  micro-organism  enters  the  diges- 
tive tube  soon  after  birth,  it  is  never  free  from  bacteria ;  and  their 
multiplication  in  one  part  of  it  rather  than  another  depends  not  so 
much  on  the  number  originally  present  to  start  the  process,  as  on 
the  conditions  which  encourage  or  restrain  their  increase. 

A  certain  amount  of  already  emulsified  fats  is  broken  up  into 
their  fatty  acids  and  glycerin  in  the  stomach,  unemulsified  fats 
entirely  by  the  fat-splitting  ferment  of  the  pancreatic  juice.  The 
acids  will  form  soaps  with  alkalies  wherever  they  meet  them  in  the 
intestinal  contents,  or  even  in  the  mucous  membrane.  A  portion 
of  those  soluble  soaps  may  be  immediately  absorbed;  the  rest  will 
aid  in  the  emulsification  of  the  fats  not  yet  chemically  decomposed, 
and  thus  greatly  hasten  the  fat-splitting  action  of  the  pancreatic 
juice.     The  phosphatides  are  in  all  probability  acted  upon  in  the 


4i6  DIGESTION 

alimentary  canal  much  in  the  same  way  as  the  fats.  Lecithin  is 
decomposed  by  pancreatic  and  intestinal  juice  into  fatty  acids  and 
glyceryl-phosphoric  acid,  and  cholin  is  liberated.  As  regards  the 
behaviour  of  the  sterins  of  the  food  little  is  known,  but  it  is  not 
unlikely  that  their  esters  are  split  up,  and  the  sterins  thus  set  free 
as  well  as  those  originally  free  in  the  food  may  then  be  absorbed, 
in  part  at  least,  without  further  change.  The  starch  and  dextrin 
which  have  escaped  the  action  of  the  saliva  are  changed  into 
maltose  by  the  amylase  of  the  pancreatic  juice,  and  the  maltose 
into  dextrose  by  the  maltase  of  the  same  secretion  and  of  the  succus 
entericus. 

The  succus  entericus,  in  addition  to  its  important  functions 
already  mentioned,  aids  as  an  alkaline  liquid  in  lessening  the  acidity 
of  the  chyme  and  establishing  the  reaction  favourable  to  intestinal 
digestion.  It  will  convert  into  monosaccharides  any  cane-sugar, 
maltose,  or  lactose,  which  may  reach  the  intestine;  but  it  cannot 
be  doubted  that  some  cane-sugar  may  be  absorbed  by  the  stomach, 
after  being  inverted  by  the  hydrochloric  acid  of  the  gastric  juice 
or  by  inverting  ferments  taken  in  with  the  food,  or  on  its  way 
through  the  gastric  walls. 

Upon  the  whole  no  great  amount  of  water  is  absorbed  in  the  small 
intestine,  or  at  least  the  loss  is  balanced  by  the  gain,  for  the  intestinal 
contents  are  as  concentrated  in  the  duodenum  as  in  the  ileum.  But 
as  soon  as  they  pass  beyond  the  ileo-caecal  valve  water  is  rapidly 
absorbed,  and  the  contents  thicken  into  normal  faeces,  to  which  the 
chief  contribution  of  the  large  intestine  is  mucin,  secreted  by  the 
vast  number  of  goblet  cells  in  its  Lieberkiihn's  crypts. 

Bacterial  Digestion. — So  far  we  have  paid  no  special  attention  to 
other  than  the  soluble  ferments  of  the  digestive  tract,  although 
we  have  incidentally  mentioned  the  action  of  the  lactic  acid  bacilli 
on  carbo-hydrates  and  of  the  fat-splitting  bacteria  on  fats.  It  is 
now  necessary  to  recognize  that  the  presence  of  bacteria  is  an 
absolutely  constant  feature  of  digestion ;  and  although  their  action 
must  in  part  be  looked  upon  as  a  necessary  evil  which  the  organism 
has  to  endure,  against  the  consequences  of  which  it  has  to  struggle, 
and  to  which  in  all  probability  it  has  to  a  great  extent  adapted 
itself,  it  is  not  unlikely  that  in  part  it  may  be  ancillary  to  the  pro- 
cesses of  aseptic  digestion.  But  bacteria  are  not  essential  (in  mam- 
mals, at  any  rate,  living  on  milk),  as  some  have  supposed.  For  it 
has  been  shown  that  a  young  guinea-pig,  taken  by  Caesarean  section 
from  its  mother's  uterus  with  elaborate  aseptic  precautions,  and 
fed  in  an  aseptic  space  on  sterile  milk,  grew  apparently  as  fast  as  one 
of  its  sisters  brought  up  in  the  orthodox  microbic  way.  The  ah- 
mentary  canal  remained  free  from  bacteria  (Nuttall  and  Thierfelder). 
On  the  other  hand,  chickens  hatched  from  sterile  eggs  and  kept  in 
a  sterile  enclosure  lived,  indeed,  for  a  time,  but  did  not  thrive  in 


SURVEY  OF  DIGESTION  AS  A    WHOLE  417 

comparison  with  the  control  animals,  and  died  at  latest  after  eighteen 
days  (Schottelius).  It  is  probable  that  the  difference  in  the  results 
is  to  be  attributed  to  the  difference  in  the  food,  purely  vegetable 
food  requiring  the  aid  of  bacteria  for  its  proper  digestion,  especially 
for  the  decomposition  of  the  cellulose,  while  an  easily-digestible 
food  hke  milk  does  not. 

Among  the  more  important  actions  of  bacteria  on  the  protein 
food-products  in  the  intestines  may  be  mentioned  the  formation 
of  indol,  phenol,  and  skatol,  the  first  having  tyrosin  for  its  precursor, 
and  being  itself  after  absorption  the  precursor  of  the  indican  in  the 
urine;  the  second  being  to  a  small  extent  thrown  out  with  the  faeces, 
but  chiefly  absorbed  and  eliminated  by  the  kidneys  as  an  aromatic 
compound  of  sulphuric  acid;  the  third  passing  out  mainly  in  the 
faeces. 

The  view  put  forward  by  Metchnikoff,  that  in  the  putrefactive 
bacteria  of  the  intestine  the  body  carries  within  itself  the  seeds  of 
premature  decay,  owing  to  the  harmful  effects  of  absorbed  products 
of  decomposed  protein,  cannot  be  looked  upon  as  established, 
although  certainly  the  prophylaxis  suggested  by  him  (the  increase 
of  the  lactic  acid  content  of  the  intestine  by  the  addition  of  sour 
rnilk,  butter-milk,  etc.,  to  the  diet)  might  well  be  a  useful  modifica- 
tion of  the  dietetic  habits  of  many  persons,  especially  if  associated 
with  a  reduction  in  the  total  amount  of  protein  consumed.  That 
the  intestinal  contents  may  include  substances  capable  of  inducing 
severe  toxic  symptoms  if  absorbed  unchanged  scarcely  needs  prooi 
Filtered  extracts  of  faeces  from  normal  persons  made  with  salt 
solution  cause,  when  injected  in  small  amounts  into  the  circulation 
of  dogs,  a  fall  of  blood-pressure  which  may  be  speedily  recovered 
from  or  may  be  quickly  fatal  according  to  the  specimen  (Fig.  170). 

The  large  intestine  is  the  chosen  haunt  of  the  bacteria  of  the 
alimentary  canal;  they  swarm  in  the  faeces,  and  by  their  influence, 
especially  in  the  caecum  of  herbivora,  but  also  to  some  extent  in 
man,  even  cellulose  is  broken  up,  the  final  products  comprising 
certain  fatty  acids,  such  as  butyric,  acetic  and  valerianic  acids, 
carbon  dioxide  and  marsh  gas.  A  cellulose-dissolving  enzyme  of 
great  activity  is  present  in  the  hepatic  secretion  of  the  snail,  which 
rapidly  produces  sugar  from  that  polysaccharide.  Dextrose  is  also 
formed  when  it  is  hydrolysed  by  dilute  acid.  Apart  from  the  im- 
portance of  solution  of  the  cellulose  in  facilitating  the  action  of  the 
digestive  juices  on  the  starch  and  other  nutrient  materials  enclosed 
by  it,  it  can  be  assumed  that  some  of  the  intermediate  products  of 
its  hydrolysis  by  the  bacteria — e.g.,  bodies  analogous  to  the  dex- 
trins  which  appear  in  the  hydrolysis  of  starch — can  be  acted  on  by 
the  ferments  of  the  succus  entericus  and  the  pancreatic  juice,  so 
as  to  form  dextrose,  which  on  absorption  then  takes  its  place  in 
the  carbo-hydrate  metabolism  just  as  if  it  had  been  derived  from 

-27 


4i8 


DIGESTION 


starch.  In  the  herbivora  the  contribution  thus  made  to  the  nutri- 
tion of  the  animal  may  be  of  considerable  importance;  in  omnivora 
it  is  not  negligible.  In  man  as  much  as  40  per  cent,  of  the  cellulose 
of  young  vegetables  is  said  to  be  capable  of  assimilation.  In  car- 
nivorous animals,  however,  it  appears  that  cellulose  when  taken  in 
the  food  is  quantitatively  excreted  in  the  fjeces.  In  addition  to 
the  action  of  the  intestinal  flora  on  cellulose,  certain  of  the  bacteria 
of  the  ahmentary  canal  affect  some  of  the  other  carbo-hydrates  in  a 


Fig.  170. — Eflect  of  Extract  of  Faeces  on  Blood-Pressure, 
at  2.    Time-trHce,  seconds. 


The  extract  was  injected 


not  unimportant  way.     Dextrose,  for  instance,  can  be  decomposed 
into  two  molecules  of  lactic  acid,  according  to  the  equation 

C6Hi20e  =  2C3H603. 

This  is  called  the  lactic  acid  fermentation,  and  is  due  to  a  special 
bacillus. 

Another  micro-organism  splits  up  dextrose  into  butyric  acid, 
carbon  dioxide  and  hydrogen,  the  so-called  butyric  acid  fermenta- 
tion, according  to  the  equation 

QHiaOg  =  C4H8O2  +  2CO2  +  2H2. 

The  contents  of  the  large  bowel  are  generally  acid  from  the 
products  of  bacterial  action,  although  the  wall  itself  is  alkaline. 

Faeces. — In  addition  to  mucin,  secreted  mainly  by  the  large 
intestine,  the  fseces  consist  of  indigestible  remnants  of  the  food,  such 
as  elastic  fibres,  spiral  vessels  of  plants,  and  in  general  all  vegetable 
structures  chiefly  composed  of  cellulose.  They  are  coloured  with  a 
pigment,  stercobilin,  derived  from  the  bile-pigments.  Stercobilin 
is  identical  with  urobilin,  which  forms  a  common,  though  not  an 


SURVEY  OF  DIGESTION  AS  A   WHOLE  4 19 

invariable,  constituent  of  bile  itself.  A  portion  of  it  is  absorbed  by 
the  intestine  and  then  excreted  in  the  urine,  the  urobilin  in  which 
is  often  much  increased  in  fever  ('  febrile  '  urobilin).  No  bilirubin 
or  biliverdin  occurs  in  normal  faeces,  although  pathologically  they 
may  be  present.  The  dark  colour  of  the  faeces  with  a  meat  diet  is 
due  to  haematin  and  sulphide  of  iron,  the  latter  being  formed  by 
the  action  of  the  sulphuretted  hydrogen  which  is  constantly  present 
in  the  large  intestine  on  the  organic  compounds  of  iron  contained  in 
the  food  or  in  the  secretions  of  the  alimentary  canal.  A  small 
amount  of  altered  bile-acids  and  their  products  is  also  found;  and 
in  respect  to  these,  and  to  the  altered  pigments,  bile  is  an  excretion. 
And  although  its  entrance  into  the  upper  instead  of  the  lower  end 
of  the  intestine,  the  ascertained  importance  of  its  function  in  diges- 
tion, and  the  fact  that  the  greater  part  of  the  bile-salts  is  reabsorbed, 
show  that  in  the  adult  it  is  very  far  from  being  solely  a  waste  product, 
the  equally  cogent  fact,  that  the  intestine  of  the  new-bom  child 
is  filled  with  what  is  practically  concentrated  bile  {meconium), 
proves  that  it  is  just  as  far  from  being  purely  a  digestive  juice. 
Skatol  and  other  bodies,  formed  by  putrefactive  changes  in  the 
proteins  of  the  food,  are  also  present  in  the  faeces,  and  are  responsible 
for  the  faecal  odour.  Masses  of  bacteria  are  invariably  present,  and 
often  make  up  a  very  considerable  proportion  of  the  total  faecal 
solids.  Of  the  inorganic  substances  in  faeces  the  numerous  crystals 
of  triple  phosphate  are  the  most  characteristic.  When  the  diet  is 
too  large,  or  contains  too  much  of  a  particular  kind  of  food,  a  con- 
siderable quantity  of  digestible  material  may  be  found  in  the  faeces — 
e.g.,  muscular  fibres  and  fat.  But  it  should  be  remembered  that 
under  all  circumstances  the  composition  of  the  faeces  differs  from 
that  of  the  food.  The  intestinal  contribution  is  always  an  important 
one,  although  relatively  more  important  with  a  flesh  than  with  a 
vegetable  diet.  The  purin  bases  normally  found  in  human  faeces 
come  both  from  the  food  directly  and  from  the  metabolism  of 
the  tissues.  They  are  increased  in  amount  on  a  diet  rich  in 
purin  bodies  (such  as  meat  extract  or  thymus),  but  are  also  formed 
on  a  diet  like  milk,  from  which  purin  bases  cannot  be  obtained. 
An  interesting  constituent  of  faeces  on  which  hght  has  recently  been 
thrown,  especially  by  the  researches  of  Gardner,  is  the  so-called  copro- 
sterin  (dihydrocholesterin),  which  appears  to  be  produced  from 
cholesterin  by  reduction,  probably  under  the  influence  of  bacteria, 
and  perhaps  also  from  the  phytosterins  of  vegetable  food. 


CHAPTER   VII 
ABSORPTION 

Section  I. — Preliminary  Physico-Chemical  Data. 

Imbibition,  or  molecular  imbibition,  is  the  term  applied  to  the  en- 
trance of  liquid  into  a  colloid,  without  the  loss  of  its  properties  as  a  solid, 
when  no  preformed  capillary  spaces  are  present.  The  entrance  of  water 
into  a  piece  of  gelatin,  or  an  epidermic  scale,  is  an  example  of  molecular 
imbibition.  Most  animal  and  vegetable  tissues  possess  this  property, 
which  is  believed  to  be  of  importance  in  such  physiological  processes  as 
absorption,  secretion,  and  the  excretion  of  water  from  the  lungs  and 
skin.  The  process  by  which  liquid  passes  into  a  solid  with  preformed 
capillary  spaces — e.g.,  a  sponge — is  sometimes  spoken  of  as  capillary 
imbibition. 

Diffusion. — When  a  solution  of  a  substance  is  placed  in  a  vessel,  and 
a  layer  of  water  carefully  run  in  on  the  top  of  it,  it  is  found  after  a  time 
that  the  dissolved  substance  has  spread  itself  through  the  water,  and 
that  the  composition  of  the  mixture  is  uniform  throughout.  The 
result  is  the  same  when  two  solutions  containing  different  proportions 
of  the  same  substance,  or  containing  different  substances,  are  placed  in 
contact.  The  phenomenon  is  called  diffusion.  The  time  required  for 
complete  diffusion  is  comparatively  short  in  the  case  of  a  substance  like 
hydrochloric  acid  or  sodium  chloride,  exceedingly  long  in  the  case  of 
albumin  or  gum.  In  both  it  is  more  rapid  at  a  high  temperature  than 
at  a  low. 

Osmosis. — If  the  solution  be  separated  from  water  by  a  membrane 
absolutely  or  relatively  impermeable  to  the  dissolved  substance,  but 
permeable  to  water,  water  passes  through  the  membrane  into  the  solu- 
tion. This  phenomenon  is  called  osmosis.  E.g.,  a  membrane  of  ferro- 
cyanide  of  copper,  nearly  impermeable  to  cane-sugar,  can  be  formed 
in  the  pores  of  an  unglazed  porcelain  pot  by  allowing  potassium  ferro- 
cyanide  and  cupric  sulphate  to  come  in  contact  there.  If  the  pot  is 
filled  with,  say,  a  i  per  cent,  solution  of  cane-sugar,  closed  by  a  suitable 
stopper,  connected  to  a  manometer,  and  then  placed  in  a  vessel  of  water, 
water  passes  into  it  till  the  pressure  indicated  by  the  manometer  rises 
to  a  certain  height.  With  a  2  per  cent,  solution  it  reaches  twice  this 
height,  and  in  general  the  osmotic  pressure,  as  it  is  called,  is  in  anj' 
solution  proportional  to  the  molecular  concentration*  of  the  solution, 

*  The  molecular  concentration  is  strictly  defined  as  the  number  of 
grammes  of  the  dissolved  substance  in  a  litre  of  the  solution  divided  by  the 
gramme-molecular  weight.  The  gramme-molecular  weight,  or  gramme 
molecule,  is  the  number  of  grammes  corresponding  to  the  molecular  weight. 
Thus,  the  gramme-molecular  weight  of  sodium  chloride  (NaCl)  is  58-36 
grammes,  and  of  cane-sugar  {Ci2H220]i),  342  grammes. 

420 


PRELIMINARY  PHYSICO-CHEMICAL  DATA 


421 


or,  in  other  words,  to  the  number  of  molecules  of  the  dissolved  substance 
in  a  given  volume  of  the  solution.  If  in  this  sentence  we  substitute 
'  gaseous  pressure  '  for  '  osmotic  pressure,'  and  '  gas  '  for  '  solution,' 
we  have  a  statement  of  Boyle's  law,  which  asserts  that  the  pressure  of  a 
gas  is  proportional  to  its  density.  Indeed,  it  has  been  shown  that  the 
osmotic  pressure  of  the  dissolved  substance  is  the  same  as  the  pressure 
that  would  be  exerted  by  a  gas,  say  hydrogen,  if  all  the  water  were 
removed,  and  a  molecule  of  hydrogen  substituted  for  each  molecule  of 
the  substance,  or  as  would  be  exerted  by  the  substance  itself  if,  after 
removal  of  the  solvent,  it  could  be  left  as  a  gas  filling  the 
same  volume.  And  the  osmotic  pressure  of  a  solution  of 
one  substance  is  the  same  as  that  of  a  solution  of  any 
other  substance  which  contains  in  a  given  volume  the 
same  number  of  molecules  of  the  dissolved  substance. 
In  other  words,  the  osmotic  pressure  is  not  dependent  on 
the  nature,  but  on  the  molecular  concentration,  of  the 
substance.  The  analogy  of  the  laws  of  osmotic  to  those 
of  gaseous  pressure  becomes  still  more  obvious  when 
it  is  added  that  the  osmotic  pressure  of  a  substance  with 
any  given  molecular  concentration  is  proportional  to  the 
absolute  temperature  ;  and  that  when  a  solution  contains 
more  than  one  dissolved  substance  the  total  osmotic  pres- 
sure is  the  sum  of  the  partial  osmotic  pressures 
which  each  substance  would  exert  if  it  were 
present  alone  in  the  same  volume  of  the  solution. 
The  osmotic  pressure  of  a  solution  may  reach 
an  enormous  amount.  Thus,  a  i  per  cent,  solu- 
tion of  cane-sugar  has  a  pressure  at  0°  C.  of 
493  mm.  of  mercury.  A  10  per  cent,  solution 
of  cane-sugar  would  have  an  osmotic  pressure  of 
more  than  six  atmospheres,  and  a  17  per  cent, 
solution  of  ammonia  a  pressure  of  no  less  than 
224  atmospheres.  The  manner  in  which  the 
phenomenon  known  as  osmotic  pressure  is  de- 
veloped is  not  definitely  known.  One  theory 
attributes  it  to  the  attraction  between  the 
dissolved  molecules  and  the  molecules  of  the 
solvent  on  the  other  side  of  the  membrane. 
The  most  commonly  accepted  view  is  that  the 
osmotic  pressure  is  due  to  the  kinetic  energy 
of  the  moving  molecules.  Where  the  mole- 
cules are  hindered  from  passing  a  bounding 
membrane,  the  pressure  exerted  by  their  im- 
pacts on  the  boundary  is  greater  than  where 
the  membrane  is  easily  permeable,  because  in 
the  latter  case  many  of  the  molecules  pass 
through,  carrying  with  them  their  kinetic 
energy.  The  pressure  must  be  still  less  when 
a  dissolved  substance  diffuses  freely  into  water; 
but  however  small  it  may  become,  it  is  in  the  same  force  which  gives 
rise  to  the  osmotic  pressure  of  the  molecules  of  the  dissolved  substance 
that  the  cause  of  diffusion  must  be  sought.  Recently  interest  in  the 
nature  of  the  membrane  itself  as  an  important  factor  in  osmosis  has  been 
revived  (Kahlenbcrg,  Armstrong,  etc.).  There  are  many  facts  which 
indicate  that  in  physiological  processes  the  affinity  of  the  dissolved  sub- 
stances for.  or  their  solubility  in,  the  cell  envelopes  or  the  cytoplasm 
plays  an  important  role. 


Fig.  171.  —  Beckmann'^ 
Apparatus.  For  de- 
scription, see  p.  521. 


422  ABSORPTION 

It  is  as  yet  impossible  or  at  least  very  difficult  to  directly  measure 
the  osmotic  pressure  with  accuracy  by  means  of  a  semi-permeable  mem- 
brane. Recourse  is  therefore  had  to  indirect  methods,  especially  one 
which  depends  on  the  fact  that  the  freezing-point  of  a  solution  is  lower 
than  that  of  the  solvent,  salt  water,  e.g.,  freezing  at  a  lower  temperature 
than  fresh  water.  The  amount  by  which  the  freezing-point  is  lowered 
depends  on  the  molecular  concentration  of  the  dissolved  substance,  to 
which,  as  we  have  seen,  the  osmotic  pressure  is  also  proportional.  When 
a  gramme -molecule  of  a  substance  is  dissolved  in  water,  and  the  volume 
made  up  to  a  litre,  the  freezing-point  is  lowered  by  i'86°  C. ;  the  osmotic 
pressure  is  22-35  atmospheres  (16, 986  mm.  of  mercur}').  It  is  therefore 
easy  to  calculate  the  osmotic  pressure  of  any  solution  if  we  know  the 
amount  by  which  its  freezing-point  is  lowered.  A  i  per  cent,  solution  of 
cane-sugar,  for  example,  would  freeze  at  about  —  0-054°  C.     Its  osmotic 

pressure  =  — >\rX  16,986=493  mm.  of  mercury. 

A  convenient  apparatus  for  making  freezing-point  measurements  is 
shown  in  Fig.  171.  The  details  of  the  method  are  given  in  the  Practical 
Exercises,  p.  521. 

The  osmotic  pressure  of  different  solutions  may  also  be  compared 
by  observing  the  effect  produced  on  certain  vegetable  and  animal  cells. 
When  a  solution  with  a  greater  osmotic  pressure  than  the  cell-sap  (a 
hyperisotonic  solution)  is  left  for  a  time  in  contact  with  certain  cells  in 
tile  leaf  of  Tradescantia  discolor,  plasmolysis  occurs— that  is,  the  proto- 
plasm loses  water  and  shrinks  away  from  the  cell- wall.  If  the  osmotic 
pressure  of  the  solution  is  lower  than  that  of  the  coloured  cell-sap 
{hypoisotonic  solution),  no  shrinking  of  the  protoplasm  takes  place.  By 
using  a  number  of  solutions  of  the  same  substance  but  of  different 
strength,  two  can  be  found,  the  stronger  of  which  causes  plasmolysis, 
and  the  weaker  not.  Between  these  lies  the  solution  which  is  isotonic 
with  the  cell-sap — that  is,  has  the  same  molecular  concentration  and 
osmotic  pressure.  The  strength  of  an  isotonic  solution  of  some  other 
substance  can  then  be  determined  in  the  same  way  with  sections  from 
the  same  leaf. 

Animal  cells  (red  blood-coi'puscles)  may  also  be  employed,  the  libera- 
tion of  haemoglobin  or  the  swelling  of  the  corpuscles,  as  measured  by 
the  haematocrite  (p.  27),  being  taken  as  evidence  that  the  solution  in 
contact  with  them  is  hypoisotonic  to  the  contents  of  the  corpuscles. 
Here  we  may  suppose  that  the  impacts  of  the  molecules  of  the  salts  of 
the  corpuscle  on  the  inside  of  its  envelope,  not  being  balanced  by 
similar  impacts  on  the  outside,  tend  to  distend  it,  and  thus  to  create  a 
potential  vacuum  for  the  surrounding  water,  which  accordingly  enters. 
If  the  corpuscles  shrink,  the  solution  is  hyperisotonic  to  their  contents. 
But  since  the  cells  are  much  more  permeable  to  certain  substances  than 
to  others,  this  method  does  not  always  yield  trustworthy  results. 

Electroljrtes. — We  have  said  that  the  osmotic  pressure  is  proportional 
to  the  concentration  of  the  solution,  but  this  statement  must  now  be 
qualified.  For  certain  compounds,  including  all  inorganic  salts  and 
many  organic  substances,  the  osmotic  pressure  decreases  less  rapidly 
than  the  theoretical  molecular  concentration  as  the  solution  is  diluted. 
The  explanation  is  that  in  solution  some  of  the  molecules  of  these  bodies 
are  broken  up  into  simpler  groups  or  single  atoms,  called  ions.  Each 
ion  exerts  the  same  osmotic  pressure  as  the  molecule  did  before.  The 
proportion  between  the  average  number  of  these  dissociated  molecules 
and  of  ordinary  molecules  is  constant  for  a  given  concentration  of  the 
solution  and  a  given  temperature.  But  as  the  solution  is  diluted,  the 
proportion  of  dissociated  molecules  becomes  greater.     The  bodies  which 


PRELIMINARY  PHYSICO-CHEMICAL  DATA  423 

behave  in  this  way  are  electrolytes — that  is,  their  solutions  conduct  a 
current  of  electricity;  bodies  which  do  not  exhibit  this  behaviour  do 
not  conduct  in  solution.  And  there  are  many  reasons  for  believing 
that  the  dissociation  of  the  electrolytes  is  the  essential  thing  in  elec- 
trolytic conduction.  We  may  suppose  that  in  a  solution  of.  an  electro- 
lyte—sodium chloride,  for  instance — a  certain  number  of  the  molecules 
fall  asunder  into  a  kalion  (Na4-),*  carrying  a  charge  of  positive  elec- 
tricity, and  an  anion  (CI—  ),  carrying  an  equal  negative  charge.  These 
electrical  charges,  it  must  be  remembered,  are  not  created  by  the 
passage  of  a  current  through  the  solution.  We  do  not  know  how  they 
arise,  but  the  ions  must  be  supposed  to  be  electrically  charged  at  the 
moment  when  the  molecule  is  broken  up.  .And  the  ions  of  different  sub- 
stances must  each  be  supposed  to  carry  the  same  quantity  of  electricity. 
But  since  they  are  all  wandering  freely  in  the  solution,  no  excess  of 
negative  or  of  positive  electricity  can  accumulate  at  any  part  of  it — in 
other  words,  no  difference  of  potential  can  exist.  When  electrodes 
connected  with  a  voltaic  battery  are  dipped  into  a  solution  of  an  elec- 
trolyte, a  difference  of  potential,  an  electrical  slope,  is  established  in  the 
liquid,  and  the  positively  charged  kations  are  compelled  to  wander 
towards  the  negative  pole,  the  negatively  charged  anions  towards  the 
positive  pole.  In  this  way  that  movement  of  electricity  which  is  called 
a  current  is  maintained  in  the  solution.  It  is  clear  that  the  greater 
the  number  of  ions,  and  the  faster  they  move  in  the  solution,  the  greater 
will  be  the  quantity  of  electricity  carried  to  the  electrodes  in  a  given 
time,  when  the  difference  of  potential  between  the  electrodes,  or  the 
steepness  of  the  electric  slope,  remains  constant.  In  other  words,  the 
specific  conductivity  of  a  solution  of  an  electrolyte  varies  as  the  number 
of  dissociated  molecules  in  a  given  volume  and  the  speed  of  the  ions. 
It  increases  up  to  a  certain  point  with  the  concentration,  because  the 
absolute  number  of  dissociated  molecules  in  a  given  volume  increases. 
The  molecular  conductivity — that  is,  the  conductivity  per  molecule,  or, 
strictly,  the  ratio  of  the  specific  conductivity  to  the  molecular  concen- 
tration— increases  with  the  dilution,  because  the  relative  number  of 
dissociated  molecules,  as  compared  with  undissociated,  increases.  At 
a  certain  degree  of  dilution  the  molecular  conductivity  reaches  its 
maximum,  for  all  the  molecules  are  dissociated.  The  ratio  of  the 
molecular  conductivity  of  any  given  solution  to  this  maximum  or 
limiting  value  is  therefore  a  measure  of  the  proportion  between  the 
number  of  dissociated,  and  the  total  number  of  molecules.  The  molec- 
ular conductivity  of  the  salts  dissolved  in  the  liquids  of  the  animal 
body,  for  the  degree  of  dilution  in  which  they  exist  there,  is  such  that 
we  must  assume  them  to  be  for  the  most  part  dissociated. 

Surface  Tension, — This  is  a  property  of  surfaces  which  is  typically 
illustrated  in  such  instances  as  a  globule  of  mercury,  a  drop  of  water 
on  a  greasy  slide,  or  a  drop  of  oil  suspended  in  a  liquid  with  which  it 
does  not  mix.  The  tendency  of  such  drops  to  assume  the  spherical 
form  when  not  large  enough  to  be  distorted  by  gravity  is  due  to  the 
fact  that  the  surface  layer  is  under  a  certain  tension  in  virtue  of  which 
it  strives  to  contract  and  to  render  the  surface  of  the  drop  as  small  as 

*  It  has  been  shown  that  the  chemical  atoms  themselves  are  not  homo- 
geneous, but  are  all  built  up  of  simpler  particles  and  possess  a  certain  struc- 
ture. All  atoms,  e.g.,  contain  electrons,  minute  particles  charged  with  negative 
electricity.  The  number  of  electrons  in  an  atom  appears  to  be  not  far  from 
half  its  atomic  weight.  Thus  in  the  carbon  atom  there  are  6  electrons,  in  the 
oxygen  atom  8,  and  in  the  hydrogen  atom  probably  only  i.  There  is 
evidence  that  the  electrons  in  the  atom  are  divided  into  groups  or  rings 
one  within  another  (Thomson). 


424  ABSORPTION 

possible,  just  as  if  it  were  a  stretched  elastic  membrane.  The  cause 
of  this  tension  is  to  be  sought  in  the  mutual  attraction  exerted  by  mole- 
cules which  are  very  close  to  each  other.  This  molecular  pull  is 
enormously  strong.  It  has  been  calculated,  for  instance,  that  the 
so-called  internal  pressure  which  is  due  to  it  is  in  the  case  of  water  not 
less  than  23,000  atmospheres.  In  the  interior  of  the  drop  each  mole- 
cule, being  surrounded  by  other  molecules,  is  pulled  by  this  attractive 
force  equally  in  all  directions — that  is  to  say,  on  the  whole  it  is  not 
pulled  at  all,  since  the  pulls  of  all  the  surrounding  molecules  balance 
each  other.  At  the  free  surface,  on  the  contrary,  the  molecules  are 
pulled  towards  the  surface,  but  not  away  from  it,  and  the  pull  of  the 
molecules  below  the  surface  layer  is  not  balanced  by  the  pull  of  mole- 
cules above  it.  The  resultant  tension  on  this  layer  is  the  surface  tension. 
Changes  in  the  amount  of  this  surface  tension  in  the  case  of  a  given 
liquid  can  be  produced  by  bringing  gases,  solids,  or  other  liquids  into 
contact  with  the  surface  layer — that  is,  by  bringing  molecules  of  other 
substances  so  near  the  surface  molecules  of  the  liquid  that  they  can 
attract  them,  and  so  to  a  greater  or  less  degree,  depending  upon  the 
nature  of  the  substances,  balance  the  attraction  of  the  molecules 
beneath  the  surface  of  the  drop.  Another  way  in  which  the  surface 
tension  can  be  altered  is  by  changing  the  temperature.  The  higher 
the  temperature,  the  greater  is  the  average  velocity  with  which  the 
molecules  of  the  liquid  are  moving,  and  the  greater  the  average  distance 
between  the  molecules  (expressed  as  the  expansion  of  the  liquid) .  Increase 
of  temperature  therefore  causes  the  molecules,  through  the  kinetic 
energy  of  heat  imparted  to  them,  say,  from  an  external  source,  to 
repel  each  other,  and  to  that  extent  counteracts  their  mutual  attrac- 
tion. Accordingly,  at  the  surface  the  tension,  which,  as  stated,  depends 
upon  the  excess  of  this  attraction  acting  towards  the  interior  of  the 
drop,  will  be  diminished.  When  the  temperature  is  diminished  the 
surface  tension  will  increase.  The  surface  tension  can  also  be  altered 
by  altering  the  electrical  charge  on  the  surface.  An  instance  of  this 
is  described  on  another  page  in  connection  with  the  capillary  electrom- 
eter (p.  702).  In  such  ways,  then,  the  surface  tension  at  the  inter- 
face where  the  cells  lining  the  intestine  come  into  contact  with  the 
contents  of  the  gut  or  with  the  tissue  lymph,  or  at  the  interfaces  within 
the  cells  where  solid  and  liquid  '  phases  '  come  into  contact  with  each 
other  or  where  different  liquids  touch,  may  undergo  alterations  in 
either  direction.  If  the  tension  of  the  surface  is  altc-red,  the  surface 
energy  or  power  of  doing  work  inherent  in  the  existence  of  this  tension 
will,  of  course,  be  altered  too.  In  this  way  the  energy,  or  a  portion  of 
it,  which  is  unquestionably  expended  in  absorption  may  be  supplied 
ultimately  at  the  expense  of  the  chemical  energy  of  cell  constituents 
or  of  food  substances  on  their  way  through  the  cells,  by  means  of  which 
the  original  surface  tensions  are  restored.  It  has  been  surmised  that 
changes  of  surface  tension  may  also  be  concerned  in  the  secretion  of 
glands,  in  muscular  contraction  (p.  718),  and  other  functions  (Macallum, 
Bernstein,  etc.). 

Adsorption. — Connected  with  the  peculiar  properties  of  surfaces 
referred  to  in  the  last  paragraph  are  certain  phenomena  spoken  of  as 
adsorption  phenomena.  Adsorption  is  typically  seen  when  a  solid  in 
such  a  form  that  the  surface  is  greatly  increased  {e.g.,  a  fine  powder  or 
a  colloidal  solution  in  which  the  substance  is  suspended  in  the  form 
of  exceedingly  small  particles)  is  placed  in  contact  with  a  gas  or  a 
solution.  There  occurs  a  diminution  in  the  concentration  of  the  gas 
or  the  dissolved  substance,  and  a  corresponding  accumulation  of  it  on 
the  su«*ace  of  the  solid.     Equilibrium  is  rapidly  established,  and  the 


MECHANISM  OF  ABSORPTION  425 

characteristic  tiling  about  adsorption  is  that  at  the  equilibrium-point 
the  concentration  of  the  dissolved  substance  (or  the  gah>j  on  the  surface 
is  immensely  greater  than  in  the  general  mass  ofthc  solution.  The  con- 
centration on  the  surface  can,  indeed,  be  increased  by  increasing  the 
concentration  of  the  solution,  but  in  a  far  smaller  proportion.  Accord- 
ing to  the  thermodynamic  law  enunciated  by  Willard  Gibbs,  sub- 
stances which  diminish  the  surface  tension  must  tend  to  accumulate 
at  the  surface,  and  substances  which  increase  the  surface  tension  must 
tend  to  diminish  in  concentration  at  the  surface.  If  a  small  quantity 
of  a  substance  diminishes  the  surface  tension  at  a  given  surface  more 
in  proportion  than  a  larger  quantity,  not  only  will  there  be  an  accumula- 
tion of  the  substance  at  the  surface,  but  this  will  be  proportionally 
greater  for  small  than  for  larger  concentrations  of  the  substance  in  the 
solution.  This  characteristic  feature  of  adsorption  may  thus  depend 
entirely  on  surface  forces  due  to  the  conditions  under  which  the  attrac- 
tion of  the  molecules  for  each  other  acts  at  the  surface.  It  has  not  been 
shown,  however,  that  chemical  forces  due  to  the  interaction  of  the 
electrically  charged  ions  are  not  also  concerned.  What  is  especially 
important  to  point  out  is  that  in  the  tissues  of  the  body  there  is  a 
great  development  of  surfaces.  The  cell  walls  or  cell  envelopes  come 
into  contact  with  the  tissue  lymph  or  the  contents  of  the  digestive 
tube  or  the  secretions  in  the  alveoli  of  glands  on  the  one  side,  and  the 
cell  contents  on  the  other,  and  constitute  in  the  aggregate  an  immense 
surface.  The  surfaces  separating  the  nuclei  from  the  cytoplasm,  and, 
above  all,  the  surfaces  of  the  particles  of  the  contents  of  cytoplasm 
and  nuclei  suspended  in  colloid  solution,  offer  prodigious  opportunities 
for  such  surface  phenomena  as  adsorption. 


Section  II. — Mechanism  of  Absorption. 

In  the  preceding  chapter  we  have  traced  the  food  in  its  progress 
along  the  alimentary  canal,  and  sketched  the  changes  wrought  in 
it  by  digestion.  We  have  next  to  consider  the  manner  in  which  it 
is  absorbed.  Then,  for  a  reason  which  has  already  been  explained, 
instead  of  following  its  fate  within  the  tissues,  until  it  is  once  more 
cast  out  of  the  body  in  the  form  of  waste  products,  it  will  be  best 
to  drop  the  logical  order  and  pick  up  the  other  end  of  the  clue — in 
other  words,  to  pass  from  absorption  to  excretion,  from  the  first 
step  in  metabolism  to  the  closing  act,  and  afterwards  to  return  and 
fill  in  the  interval  as  best  we  can. 

Comparative. — And  here,  first  of  all,  it  should  be  remembered  that 
the  epithelial  surfaces,  through  which  the  substances  needed  by  the 
organism  enter  it,  and  waste  products  leave  it,  are,  physiologically  con- 
sidered, outside  the  body.  The  mucous  membranes  of  the  alimentary, 
respiratory,  and  urinary  tracts  arc  in  a  sense  as  much  external  as  the 
fourth  great  division  of  the  physiological  surface,  the  skin.  The  two 
latter  surfaces  ai';  in  the  mammal  purely  excretory.  Absorption  is 
the  dominant  function  of  the  alimentary  mucous  membrane,  but  a 
certain  amount  of  excretion  also  goes  on  through  it.  The  pulmonars' 
surface  both  excretes  and  absorbs,  and  that  in  an  equal  measure.  But 
it  is  by  no  means  necessary  that  the  surface  through  which  oxygen  is 
taken  in  and  gaseous  waste  products  given  olf  should  be  buried  deep  in 
the  body,  and  communicate  only  by  a  narrow  channel  with  the  exterior. 


426  ABSORPTION 

In  the  frog  the  skin  is  largely  an  absorbing  as  well  as  an  excreting 
surface  ;  oxygen  passes  freely  in  through  it,  just  as  carbon  dioxide  passes 
freely  out.  In  most  fishes,  and  many  other  gill-bearing  animals,  the 
whole  gaseous  interchange  takes  place  through  surfaces  immersed  in 
the  surrounding  water,  and  therefore  distinctly  external.  In  certain 
forms  it  has  even  been  shown  that  the  alimentary  canal  may  serve  con- 
spicuously for  absorption  and  excretion  of  gaseous,  as  well  as  liquid 
and  solid  substances.  Still  lower  down  in  the  animal  scale,  the  surface 
of  a  single  tube  may  perform  all  the  functions  of  digestion,  absorption 
and  excretion.  Lower  still,  and  even  this  tube  is  wanting,  and  every- 
thing passes  in  and  out  through  an  external  surface  pierced  by  no  per- 
manent opsnings. 

Indeed,  even  in  man  the  functions  of  the  various  anatomical  divisions 
of  the  physiological  surface  are  not  quite  sharply  marked  off  from  each 
other.  Though  gaseous  exchange  goes  on  far  more  readily  through  the 
pulmonary  membrane  than  anywhere  else,  swallowed  oxygen  is  easily 
enough  absorbed  from  the  alimentary  canal  and  carbon  dioxide  given 
off  into  it ;  and  to  a  small  extent  these  gases  can  also  pass  through  the 
skin.  Though  water  is  excreted  chiefly  by  the  skin,  the  pulmonary 
and  the  urinary  surfaces,  and  on  the  whole  absorbed  chiefly  from  the 
digestive  tract,  there  is  no  surface  which  in  the  twenty-four  hours  pours 
out  so  much  water  as  the  mucous  membrane  of  the  stomach.  Under 
normal  conditions,  it  is  true,  by  far  the  greater  part  of  this  is  reabsorbed 
in  the  intestine,  yet  in  diarrhcea,  whether  natural  or  caused  by  purga- 
tives, the  intestines  themselves  may,  instead  of  absorbing,  contribute 
largely  to  the  excretion  of  water.  Again,  although  the  solids  of  the 
excreta  are  normally  given  off  in  far  the  greatest  quantity  in  the  urine 
and  faeces  (only  part  of  the  latter  is  truly  an  excretion,  since  much  of 
the  faeces  of  a  mixed  diet  has  never  been  physiologically  inside  the 
body  at  all),  yet  salts  and  traces  of  urea  are  constantly  found  in  the 
sweat,  and  salts  and  mucin  in  the  excretions  of  the  respiratory  tract. 
Further,  although  the  solids  and  liquids  of  the  food  are  usually  taken 
in  by  the  alimentary  mucous  surface,  it  is  possible  to  cause  substances 
of  both  kinds  to  pass  in  through  the  skin ;  and  a  certain  amount  of 
absorption  may  also  take  place  through  the  urinary  bladder.  So  that 
really  it  may  be  considered,  from  a  physiological  point  of  view,  as  more 
or  less  an  accident  that  a  man  should  absorb  his  food  by  dipping  the 
villi  of  his  intestine  into  a  digested  mass,  rather  than  by  dipping  his 
fingers  into  properly  prepared  solutions,  as  a  plant  dips  its  roots  among 
the  liquids  and  solids  of  the  soil ;  or  that  he  should  draw  air  into  organs 
lying  well  in  the  interior  of  his  thorax,  instead  of  letting  it  play  over 
special  thin  and  highly  vascular  portions  of  his  skin  ;  or  that  the  surface 
by  which  he  excretes  urea  should  be  buried  in  his  loins,  instead  of  lying 
free  upon  his  back. 

It  has  been  already  explained  that,  although  digestion  is"  a 
necessary  preliminary  to  the  absorption  of  most  of  the  solids  of 
the  food,  we  are  not  to  suppose  that  all  the  food  must  be  digested 
before  any  of  it  begins  to  be  absorbed.  On  the  contrary,  the 
two  processes  go  on  together.  As  soon  as  any  peptone,  or,  at 
least,  any  amino-acids,  have  been  formed  from  the  proteins,  or 
any  dextrose  from  the  starch,  they  begin  to  pass  out  of  the  ali- 
mentary canal ;  and  by  the  time  digestion  is  over,  absorption  is  well 
advanced. 

Even  in  the  mouth  it  has  already  begun,  although  the  amount  of 


MECHANISM  OF  ABSORPTION  427 

absor]f)tion  here  is  quite  insignificant,  and  il  is  continued  with 
greater  rapidity  in  the  stomach.  Here  a  not  inconsiderable  part 
of  the  proteins — at  least,  in  the  easily  digested  form  of  animal  food — 
a  certain  amount  of  the  sugar  representing  the  carbo-hydrates  and 
diffusible  substances  like  alcohol,  and  the  extractives  of  meat, 
which  form  an  important  part  of  most  thin  soups  and  of  beef-tea, 
are  undoubtedly  absorbed.  Water  is  very  sparingly  taken  up  by 
the  stomach.  It  is  in  the  small  intestine  that  absorption  reaches  its 
height.  The  mucous  membrane  of  this  tube  offers  an  immense 
surface,  multiplied  as  it  is  by  the  valvulae  conniventes,  and  studded 
with  innumerable  villi.  Here  the  whole  of  the  fat,  much  sugar, 
proteose  and  peptone,  or  rather  the  products  of  the  further  action 
of  the  ferments  of  the  intestine  on  these  derivatives  of  the  native 
proteins,  and  certain  constituents  of  the  bile  are  taken  in.  In  the 
large  intestine,  as  has  been  already  said,  water  and  soluble  salts  are 
chiefly  absorbed. 

What  now  is  the  mechanism  by  which  these  various  products  are 
taken  up  from  the  digestive  tube,  and  what  paths  do  they  follow  on 
their  way  to  the  tissues  ? 

Theories  of  Absorption. — Not  so  very  long  ago  it  was  supposed  by 
many  that  the  processes  of  diffusion,  osmosis  and  filtration  offered  a 
tolerably  complete  explanation  of  physiological  absorption.  At  that 
time  the  dominant  note  of  physiology  was  an  eager  appeal  to  chemistry 
and  physics  to  '  come  over  and  help  it  ' ;  and  as  new  facts  were  dis- 
covered in  these  sciences  they  were  applied,  with  a  confidence  that  was 
almost  naive,  to  the  problems  of  the  animal  organism.  The  phenomena 
of  the  passage  of  liquids  and  dissolved  solids  through  animal  membranes, 
upon  which  the  woik  of  Graham  had  cast  so  much  light,  seemed  to  find 
their  parallel  in  the  absorptive  processes  of  the  alimentary-  canal. 
And  when  digestion  was  more  deeply  studied,  facts  appeared  wliich 
seemed  to  show  tliat  its  whole  drift  was  to  increase  the  solubility  and 
diffusibility  of  the  constituents  of  the  food.  But  as  time  went  on,  and 
more  was  learnt  of  the  phenomena  of  absorption  and  the  powers  of 
cells,  these  crude  physical  theories  broke  dowTi,  and  discarded  '  vital- 
istic  '  hypotheses  began  once  more  to  arouse  attention.  Then  came 
the  investigations  of  De  Vries,  Van  'T  Hoff,  and  others  in  the  domain 
of  molecular  physics,  which  gave  to  our  notions  of  osmosis  the  precision 
that  was  wanted  before  its  relation  to  many  physiological  processes 
could  be  profitably  discussed.  At  the  present  time  it  must  be  admitted 
that  we  possess  no  full  explanation  of  absorption,  none  which  is  much 
more  than  a  confession  of  ignorance,  and  does  not  itself  need  to  be 
explained.  Yet  some  progress  has  been  made  at  least  in  defining  the 
boundary  between  what  is  clearly  known  and  what  is  still  dark,  and 
in  showing  that  familiar  physical  processes  are  not  without  influence. 
Some  physiologists,  impressed  with  the  vast  progress  of  physics  and 
chemistry,  believe  that  it  will  eventually  become  possible  to  explain 
on  mechanical  and  chemical  principles  all  the  peculiar  phenomena  which 
we  observe  in  the  passage  of  substances  through  the  walls  of  the  ali- 
mentary' canal.  As  an  aid  to  the  framing  of  practical  working  hypo- 
theses this  attitude  has  everything  m  its  favour.  Others,  taking 
account  of  the  number  and  nature  of  these  peculiarities,  oppressed  with 
the  perennial  paradox  of  vital  action,  incline  to  the  less  sanguine  view, 


428  ABSORPTION 

that  after  all  physical  explanations  have  been  exhausted,  the  real  secret  of 
the  cell  will  still  lurk  in  some  ultimate  '  vital '  property  of  structure  or  of 
function,  and  still  elude  our  search.  The  only  sense  in  which  this  attitude 
can  be  said  to  be  a  useful  one  is  that  it  presents  a  standing  protest  against 
the  acceptance  of  superficial  '  physical '  explanations  merely  because  they 
are  physical.  Both  the  optimists  and  the  pessimists,  the  adherents 
of  the  physical  and  the  adherents  of  the  vitalistic  hypothesis,  have, 
unfortunately,  as  a  rule  taken  up  an  extreme  position,  as  if  their  theories 
were  mutually  exclusive.  They  agree,  however,  in  admitting  that  the 
phenomena  of  absorption  are  essentially  connected  with  the  cells  that 
line  the  alimentary'  canal,  and  not  with  any  more  or  less  inert  '  cement  ' 
substance  between  them.  But  the  one  school  must  confess  what  the  other 
proclaims,  that  while  the  processes  carried  on  in  these  cells  are  definite, 
well  ordered,  and  evidently  guided  by  laws,  these  laws  have  as  yet 
for  the  most  part  denied  themselves  to  the  modem  physiologist,  with 
chemistry  in  one  hand  and  physics  in  the  other,  as  they  denied  them- 
selves to  his  predecessor,  equipped  only  with  his  scalpel,  his  sharp  eyes, 
and  his  mother-wit.  So  that  in  the  present  state  of  our  knowledge  all 
we  can  really  say  is  that,  while  absorption  is  certainly  aided  by  physical 
processes,  like  osmosis  and  diffusion,  possibly  by  physical  processes 
like  imbibition,  and  is  very  likely  not  unrelated  to  the  molecular  proper- 
ties of  surfaces  (surface  tension,  adsorption),  it  is  at  bottom  the  work 
of  cells  with  a  selective  permeability  which  we  do  not  fully  understand, 
or  at  least  which  we  cannot  as  yet  explain  in  terms  of  known  physical 
processes  acting  through  a  membrane  of  known  physico-chemical 
structure. 

Thus,  dissolved  substances  pass  with  equal  ease  in  either  direc- 
tion through  an  ordinary  diffusion  membrane,  but  in  general  they 
pass,  with  the  water  in  which  they  are  dissolved,  more  readily  out 
of  the  intestine  than  into  it.  This  normal  direction  of  the  stream 
is  still  maintained  for  a  considerable  time  after  stoppage  of  the 
circulation,  provided  that  the  intestine  is  kept  in  good  condition — 
for  example,  by  being  suspended  in  well-oxygenated  blood.  Water 
or  solutions  of  sodium  chloride  or  sugar  disappear  from  the  lumen. 
And  this  is  not  due  to  mere  imbibition  by  the  intestinal  wall,  but 
the  liquid  is  actually  transported  across  it.  The  theory  that  liquids 
might  be  taken  up  from  the  gut  by  imbibition,  and  the  water  then 
mechanically  removed  by  the  blood  flowing  on  the  other  side  of  the 
imbibing  cells,  is  incompatible  with  this  experiment  (Cohnheim). 
Nor  is  it  necessary  that  differences  of  concentration  of  the  dissolved 
substances  on  the  two  sides  of  the  absorbing  intestinal  membrane, 
which  would  permit  osmosis  and  diffusion  to  go  on,  should  exist. 
When  the  excised  intestine  of  a  holothurian  was  filled  with  sea- 
water  and  suspended  in  the  same  sea-water,  its  contents  continued 
to  diminish  in  bulk  for  hours  or  entirely  disappeared.  Here  a  liquid 
identical  in  composition  and  concentration  with  the  external  liquid 
was  moved  in  a  definite  direction  across  the  wall  of  the  intestine 
from  the  lumen  to  the  exterior  surface.  In  like  manner,  when  a 
piece  of  intestine  from  a  newly-killed  rabbit  is  stretched  across  a 
vessel  of  salt  solution  so  as  to  divide  it  into  two  separate  compart- 
ments, the  solution  continues  for  a  while  to  leave  the  compartment 


MECHANISM  OF  ABSORPTION  429 

to  which  the  mucosa  is  turned,  and  to  accumulate  in  the  other.    In 
the  cases  mentioned  the  transportation  of  the  Uquid  depends  upon 
the  survival  of  those  properties  of  the  mucous  membrane  which 
characterize  its  elements  as  living  cells.     For  when  the  cells  that 
line  the  intestine  are  injured  or  destroyed,   or  subjected  to  the 
action   of  certain   poisons,   absorption   from   it   is   diminished   or 
abolished.     In  the  dead  intestine  the  characteristic  set  of  the  tide 
out  of  the  lumen  across  the  mucosa  can  no  longer  be  observed.     It 
must  be  remarked  further,  in  this  connection,  that  in  its  normal  state 
the  mucous  membrane  does  not  take  up  indiscriminately  all  kinds 
of  diffusible  substances,  or  absorb  those  which  it  does  take  up  in 
the  direct  ratio  of  their  diffusibility.     Nor  does  it  reject  everything 
which  does  not  diffuse.     Albumin,  for  example,  which  does  not 
pass  through  dead  animal  membranes,  is  to  a  certain  extent  taken 
up  from  a  loop  of  intestine  without  change.     Cane-sugar   (after 
inversion)    and   dextrose   are   absorbed   more   rapidly   than   their 
velocity  of  diffusion  would  indicate,  when  compared  wath  inorganic 
salts.     Glauber's  salt  diffuses  in  water  fifteen  times  as  fast  as  cane- 
sugar,  but  cane-sugar  is  absorbed  from  the  intestines  ten  times  faster 
than  Glauber's  salt.     The  velocity  of  absorption  is  different  even 
for  simple  stereoisomeric  sugars — i.e.,  sugars  whose  molecule,  with 
the  same  number  of  atoms  combined  in  the  same  way,  has  a  dif- 
ferent form  (Nagano).     Nor  is  there  any  clear  relation  between  the 
rate  of  absorption  of  the  various  sugars  and  their  osmotic  pressure. 
Dextrose  and  cane-sugar  are  always  absorbed  in  greater  amount 
than  lactose  from  solutions  of  the  same  osmotic  pressure.     Indeed, 
as  we  shall  see,  lactose  is  practically  not  taken  up  at  all  as  such 
(p.  439),  and  in  concentrated  solutions  may  even  cause  a  reversal 
of  the  normal  movement  of  water,  and  act  as  a  purgative.     Even  the 
water,  organic  and  inorganic  solids  of  the  serum  of  an  animal,  are 
absorbed  from  a  loop  of  its  intestine  when  the  blood-pressure  in  the 
capillaries  of  the  intestinal  wall  is  considerably  greater  than  the 
pressure  in  the  cavity  of  the  gut.     Since  the  serum  in  the  intestine 
and  the  plasma  in  the  capillaries  must  be  isotonic,  and  practically 
identical  in  chemical  composition,  the  absorption  cannot  be  due 
to  ordinary  osmosis  or  diffusion.     Nor  can  it  be  due  to  filtration, 
since  the  slope  of  pressure  is  from  the  capillaries  to  the  lumen  of 
the  gut  (Reid).     It  is  therefore  extremely  difficult  to  reconcile  this 
experiment  with  any  purely  physical  theory  of  absorption.     The 
same  investigator,  summing  up  the  result  of  careful  experiments  on 
the  absorption  of  weak  solutions  of  glucose,  concludes  that,  '  with 
the  intestinal  membrane  as  normal  as  the  experimental  procedure 
will  permit,  phenomena  present  themselves  which  are  as  distinctly 
opposed   to   a   simple    physical   explanation    as  those   previously 
studied  in  the  absorption  of  serum.' 

There  is  also  evidence  that  even  during  the  absorption  of  liquids 


430  ABSORPTION 

which  undergo  no  chemical  changes  in  the  gut — e.g.,  salt  solutions 
of  different  kinds  and  different  concentrations — chemical  energy 
must  be  transformed,  and  on  no  mean  scale,  in  the  intestinal 
mucosa,  for  the  consumption  of  oxygen  and  the  production  of 
carbon  dioxide  by  the  intestine  is  markedly  increased  (Brodie  and 
Vogt). 

It  may  be  taken,  then,  as  quite  certain  that  in  absorption  from 
the  alimentary  canal  an  essential  factor  is  the  activity  of  the  living 
cells  of  the  mucosa,  which,  in  some  way  at  present  unknown,  main- 
tain the  '  set  of  the  tide  '  from  the  lumen  to  the  bloodvessels  (or 
lymph  spaces),  whether  the  slope  of  concentration  of  the  dissolved 
substances  favours  or  opposes  it,  or  when  the  concentration  is  the 
same  on  both  sides  of  the  membrane.  It  is  even  probable  that  this 
action  of  the  cells  is  much  the  most  important  of  all  the  factors 
involved.  It  would  be  highly  misleading,  however,  to  assume  thai, 
because  this  is  so,  other  factors — osmosis,  diffusion,  possibly  even 
filtration  due  to  differences  of  pressure  caused  by  the  intestinal 
movements  or  the  contractions  of  the  muscular  fibres  of  the  villi 
(p.  437) — are  of  necessity  negligible.  On  the  contrary,  these  other 
factors  cannot  be  adequately  taken  account  of,  nor  can  there  be 
any  possibility  of  assigning  to  them  their  proper  value  until  it  is 
recognized  that  their  influence  in  absorption  from  the  digestive 
tract  is  never  under  ordinary  conditions  expressed  as  a  simple  and 
uncomplicated  effect,  such  as  may  be  observed  in  experiments  with 
dead  membranes,  but,  on  the  contrary,  is  constantly  overlaid, 
thwarted,  or  totally  reversed,  by  the  special  action  of  the  cells. 
For  this  reason  the  discussion  of  the  mechanism  of  absorption  under 
the  time-honoured  captions  of  '  mechanical  or  physical  theory  ' 
versus  '  physiological  or  vital  theory,'  as  if  the  process  must  of 
necessity  be  purely  '  physical '  or  purely  '  vital,'  has  lost  interest. 
It  may  be  confidently  assumed,  indeed,  that  just  because  the 
physiological  factor  is  so  dominant,  the  familiar  physical  forces 
must  often  appear  to  exert  a  smaller  influence  than  is  really  the 
case,  and  that,  could  we  disentangle  the  currents  which  they  create 
and  sustain  from  that  steady  drift  of  material  out  of  the  lumen  of 
the  gut  maintained  at  the  expense  of  its  chemical  energy  by  the 
still  unknown  machinery  of  the  cells,  we  should  be  impressed  with 
the  magnitude  rather  than  the  insignificance  of  their  total  effect. 

The  following  attempt  by  Hober  to  analyze  on  these  lines  an  old 
experiment  of  Heidenhain,  which  the  latter  observer  had  interpreted 
as  showing  that  diffusion  and  osmosis  play  no  essential  part  in  absorp- 
tion from  the  alimentary  canal,  is  of  interest  in  this  connection.  A 
loop  of  small  intestine  was  tied  off  at  both  ends,  but  its  circulation  was 
not  otherwise  interfered  with.  Solutions  of  sodium  chloride  of  dif- 
ferent strengths  were  introduced  into  the  loop,  and  in  each  observation 
after  fifteen  minutes  the  contents  of  the  loop  were  recovered  and 
analyzed  for  the  chloride. 


MECHANISM  OF  ABSORPTION 


431 


Introduced. 

Recovered. 

• 

c.c. 

Percentage  of 
NaCl. 

Total  NaCl  in 
Grammes. 

C.C. 

Percentage  of 

NaCl. 

Total  NaCl  in 
Grammes. 

120 
120 

117 

120 

0-30 
0-50 
I -00 
1-46 

0-36 
0-60 
I-I7 

18 

35 

75 

109 

o-6o 

o-6t> 
0-90 
1-20 

0-108 
0-230 
0-670 
1-310 

Here  it  is  seen  that,  from  the  markedly  hypotonic  solutions  of  the 
first  two  observations,  sodium  chloride  was  absorbed,  of  course,  along 
with  much  water.  But  from  the  strongly  hypertonic  solution  of  the 
last  observation  some  water  was  also  taken  up,  instead  of  water  passing 
into  it  from  the  blood.  The  suggested  explanation  of  these  and  other 
data  yielded  by  the  experiment  is  that  an  osmotic  stream  of  water  out 
of  the  loop  into  the  blood  is  established  on  introduction  of  the  hypo- 
tonic solutions,  which  raises  their  percentage  of  salt,  while  in  the  case  of 
the  hypertonic  solution  a  diffusion  stream  of  sodium  chloride  is  estab- 
lished in  the  same  direction,  and  its  salt  content  falls.  The  volume  of 
the  hypotonic  solutions  in  the  loop  rapidly  diminishes  because  the 
osmotic  current  conspires  with  the  normal  '  physiological  '  drift  from 
the  lumen  outwards.  In  this  drift  both  salt  and  water  are  involved, 
as  if  the  cells  were  filters  which  maintained  through  expenditure  of 
their  own  energy  a  slope  of  hydrostatic  pressure  from  free  surface  to 
depth.  The  hypertonic  solution  diminishes  only  slowly  in  bulk,  be- 
cause the  '  physiological '  current  out  of  the  lumen  is  opposed  by  the 
osmotic  stream  of  water  into  the  lumen.  Nevertheless,  even  the  hyper- 
tonic solution  is  gradually  absorbed,  because  the  pull  of  the  cells — ^the 
suction,  if  it  may  be  so  expressed,  of  the  cellular  pump — is  powerful 
enough  to  overcome  the  osmotic  current  and  to  force  water  up  the 
slope  into  the  blood  or  into  the  tissue  liquid,  whose  osmotic  pressure  is 
not  much  more  than  half  that  of  the  solution. 

Permeability  of  the  Intestinal  Epithelium  and  Lipoid-Solubility 
of  Absorbed  Substances. — If  the  cells  of  the  intestinal  mucosa  are 
to  move  materials  out  of  the  lumen  of  the  gut,  it  is  obvious  that 
these  materials  must  first  be  able  to  enter  the  cells.  The  ease  or 
difficulty  with  which  different  substances  are  absorbed  may  there- 
fore depend  upon  the  degree  in  which  the  cells  are  permeable  for 
them.  The  question  of  the  factors  on  which  the  permeability  of 
cells  depends  has  already  been  discussed  to  some  extent  in  the  case 
of  the  coloured  blood-corpuscles.  A  famous  theory  attributes  the 
degree  of  permeability  of  erythrocytes  and  many  other  animal  and 
plant  cells  to  given  substances  to  the  degree  of  the  solubility  of 
these  substances  in  the  lipoids  which  are  supposed  to  form  the 
essential  constituents  in  the  outer  layer  or  envelope  of  cells  (Overton) 
Substances  which  are  readily  soluble  in  hpoids  are  supposed  to  gain 
an  easy  entrance  by  going  into  solution  in  the  envelope  ;  those  which 
are  insoluble  in  lipoids  are  checked  at  the  boundary.  Attempts 
have  been  made  to  apply  this  theory  to  the  explanation  of  selective 


432 


ABSORPTION 


absorption  by  the  intestine,  but  without  much  success.  The  very 
fact  that  the  theory  is  held  to  apply  to  practically  any  cell  greatly 
circumscribes  at  the  outset  its  power  of  dealing  with  cells  Hke  those 
lining  the  intestine,  which  are  adapted  to  absorb  nutrient  materials 
for  all  the  body,  and  must  necessarily  differ  in  their  permeability 
from  cells  adapted  for  some  hmited  function  involving  only  a 
limited  and  speciaUzed  nutritive  exchange.  Thus  sodium  chloride 
practically  does  not  penetrate  the  red  blood-corpuscles,  the  muscle 
fibres,  and  many  other  tissue  elements.  It  is  a  lipoid-insoluble  sub- 
stance, and  the  hpoid  theory  says  that  this  is  the  reason  why  it 
penetrates  these  cells  with  such  difficulty.  But  sodium  chloride 
must  and  does  penetrate  the  intestinal  mucosa,  and  with  consider- 
able ease,  in  order  that  the  body,  especially  its  extracellular  liquids, 
may  obtain  a  sufficient  supply  of  this  indispensable  material.  It  is 
still  a  lipoid-insoluble  substance,  and  pays  no  heed  to  the  hpoid 
theory  at  all.  It  is  perfectly  true  that  some  substances — e.g.,  ethyl 
alcohol — which  are  much  more  soluble  in  lipoids  than  sodium 
chloride,  are  also  even  more  readily  absorbed  from  the  intestine. 
It  has  been  stated  also  that,  as  regards  the  velocity  of  their  absorp- 
tion, the  three  alcohols,  glycerin,  erythrite,  and  mannite,  are  related 
to  each  other  in  the  same  way  as  in  regard  to  their  lipoid-solubility. 
There  is,  of  course,  some  reason  for  this,  and  also  some  reason  why 
ethyl  alcohol  is  taken  up  more  easily  than  salt,  but  we  do  not  know 
that  it  has  anything  to  do  with  hpoid-solubility.  If  there  is  a 
lipoid  layer  at  the  free  ends  of  the  cells  covering  the  vilU,  it  is  very 
possible  that  a  substance  soluble  in  lipoids  may  be  able  to  enter  cells 
which  would  otherwise  have  denied  it  entrance.  It  may  even  inflict 
temporary  or  permanent  injury  on  the  cells  in  doing  so,  and  may 
thus  be  taken  up  in  greater  amount  than  by  normal  cells,  and  this 
possibility  has  to  be  reckoned  with  in  giving  a  physiological  value 
to  experiments  with  materials  essentially  foreign  to  the  intestine, 
and  to  which  it  cannot  have  developed  any  adequate  adaptation. 
For  the  essential  food  materials  it  is  quite  certain  that,  apart  from 
any  general  relations  of  cell  envelope  and  environing  Hquids  which 
are  common  to  the  intestinal  and  to  other  cells,  special  relations  of 
an  adaptive  nature  have  been  developed  between  the  intestinal  cells 
and  the  very  special  hquids,  elsewhere  unknown  in  the  body,  with 
which  they  come  in  contact  in  the  lumen  of  the  gut.  It  is  unlikely 
that  the  mucosa  has  developed  a  special  adaptation  for  lipoid- 
soluble  food  materials;  it  must  have  developed  an  adaptation  for 
such  food  materials,  lipoid-soluble  or  not,  as  have  been  offered  to 
it  through  countless  ages,  and  as  are  necessary  for  the  nutrition  of 
the  organism. 

But  if  it  be  true  that  the  action  of  the  columnar  epithelium  of  the 
intestinal  mucous  membrane  in  the  absorption  of  the  food  is  in  the 
main  a  process  of  selective  secretion  such  as  is  found  in  glandular 


MECHANISM  OF  ABSORPTION  433 

organs,  an  action  which  we  may  perhaps  describe  as  making  use 
of  purely  physical  processes,  but  not  mastered  by  them,  the  possi- 
bility must  be  admitted  that  in  the  cells  of  endothelial  type  which 
line  the  serous  cavities,  the  lymphatics,  the  bloodvessels,  the  alveoli 
of  the  lungs,  and  the  Bowman's  capsules  of  the  kidney  (p.  484),  the 
element  of  secretion  may  be  less  marked,  and  more  overshadowed 
by  the  physical  factors.  And  it  may  very  plausibly  be  urged  that 
changes  of  considerable  physiological  complexity  can  only  be 
wrought  on  substances  that  have  to  pass  through  a  cell  of  con- 
siderable depth,  while  a  mere  film  of  protoplasm  suffices  for,  and 
indeed  favours,  mechanical  filtration  and  diffusion.  We  have 
already  seen  (p.  262),  in  the  case  of  the  lungs,  that  whatever  the 
complete  explanation  may  be  of  the  gaseous  exchange  which  takes 
place  through  the  alveolar  membrane,  physical  diffusion  undoubtedly 
plays  an  important  part.  We  shall  see,  too  (p.  492),  that  in  the  case 
of  the  kidney  the  endothelium  of  the  Bowman's  capsule,  although 
by  no  means  devoid  of  selective  power,  does  seem  to  have  allotted  to 
it  a  simpler  task  than  falls  to  the  share  of  the  '  rodded  '  epithelium. 

Absorption  from  the  Peritoneal  Cavity. — Further,  it  has  been  stated 
that  interchange  between  blood-serum,  circulated  artificially  in  the 
vessels  of  dogs  and  rabbits  which  have  been  dead  for  hours,  and 
liquids  introduced  into  the  peritoneal  cavity,  is  essentially  the  same 
as  in  the  living  animal,  and  can  be  explained  on  purely  physical 
principles  (Hamburger).  But  there  is  one  experiment,  at  any  rate, 
which  is  certainly  difficult  so  to  explain — viz.,  the  absorption  from 
the  peritoneal  cavity  of  sodium  chloride  solution  isotonic  with  the 
blood-serum,  an  absorption  which  goes  on  with  considerable 
rapidity.  Starling  has  supposed  that  this  is  due  to  the  circum- 
stance that  the  proteins  of  the  serum  exert  osmotic  pressure,  the 
peritoneal  membrane  being  almost  or  altogether  impermeable  for 
them  in  comparison  to  its  permeabilit\'  for  the  salt  solutions.  In 
consequence,  water  passes  into  the  bloodvessels  from  the  peritoneal 
ca\nty.  The  solution  thus  becomes  more  concentrated  as  regards 
sodium  chloride,  some  of  which  accordingly  enters  the  blood 
by  diffusion,  and  so  on.  But  even  isotonic  serum  is  absorbed 
from  the  peritoneal  cavity,  and  it  seems  to  savour  of  special  pleading 
to  suggest,  as  has  been  done,  that  this  takes  place  through  the 
lymphatics,  and  not  at  all  through  the  bloodvessels. 

Up  to  a  certain  point  an  increase  in  the  intraperitoneal  pressure 
favours  absorption,  but  beyond  this  it  hinders  it  b\'  interfering  with 
the  circulation.  The  removal  of  a  portion  of  the  fluid  in  this  con- 
dition facilitates  the  absorption  of  the  rest — a  fact  which  has  long 
been  applied  in  the  operation  of  tapping.  Ligation  of  the  thoracic 
duct  has  little  effect  on  the  fate  of  liquids  injected  into  serous 
cavities,  since  the  bloodvessels  play  the  chief  part  in  their  absorp- 
tion, just  as  strychnine,  when  injected  under  the   skin — i.e.,  into 

28 


434 


ABSORPTION 


the  lymph  spaces  of  areolar  tissue — is  taken  up  by  the  blood  and 
does  not  appear  in  the  lymph. 

But  even  if  we  admit  that  substances  can  pass,  by  physical  pro- 
cesses alone,  from  serous  cavities  into  the  blood,  and  from  the  blood 
into  serous  cavities,  this  has  little  bearing  upon  the  question  of 
intestinal  absorption.  For  we  can  hardly  put  anything  into  the 
peritoneal  cavity  which  is  not  foreign  to  it.  It  was  never  intended 
to  come  into  contact  with  the  hundred  and  one  solutions,  extracts, 
suspensions,  and  what  not,  which  the  industrious  experimenter  has 
offered  to  its  unsophisticated  endothelium.  It  cannot  possibly  have 
developed  any  high  degree  of  '  selective  '  power.  In  the  intestine 
everything  is  different.  The  mucosa  is  adapted  to  come  into 
contact  with  an  immense  variety  of  materials,  all  kinds  of  food- 
substances  mingled  with  many  kinds  of  refuse,  the  products  of 
the  action  of  numerous  digestive  ferments,  and  of  a  vigorous  and 
varied  bacterial  flora.  All  these  it  has  to  sift  and  try.  It  cannot  fail 
to  have  properties  which  suggest  a  severe  and  searching  selection. 

The  difference  between  a  serous  cavity  and  the  intestine  is  well 
illustrated  by  the  following  experiment,  in  which  the  changes  in  the 
composition  of  a  hypotonic  (3  per  cent.)  solution  of  dextrose  introduced 
into  the  peritoneal  sac  and  into  a  loop  of  intestine  respectively  were 
compared  (Cohnheim). 


Introduced. 

After                                        Recovered. 

Peritoneum  - 
Intestine  -     - 

50  C.C. 
44    » 

{,  19-5  C.C,  containing  i  percent. 
90  mins.  -        dextrose  and  0-55  per  cent. 

1        NaCl. 

f  19  C.C,  containing  3-8  per  cent. 
25     ,,      -        dextrose  and  0-04  per  cent. 

Ij      NaCl. 

Here  the  water  and  sugar  are  both  taken  up  from  the  intestine  and 
the  peritoneal  cavity;  but  while  the  sugar  concentration  in  the  serous 
sac  falls  markedly,  as  ought  to  be  the  case  if  the  sugar  is  diffusing  into 
the  blood  along  the  slope  of  concentration,  the  percentage  of  sugar  in 
the  intestine  actually  increases.  Still  more  striking  is  the  fact  that 
sodium  chloride  accumulates  in  the  peritoneal  liquid  in  a  concentration 
obviously  tending  to  equality  with  that  of  the  blood,  as  would  happen 
if  the  peritoneal  lining  were  a  dead  diffusion  membrane.  On  the  other 
hand,  practically  no  sodium  chloride  passes  into  the  lumen  of  the  gut. 

Closely  connected  with  the  question  of  absorption  from  and 
secretion  (or  transudation)  into  the  serous  cavities  is  the  question 
of  the  factors  concerned  in  the  formation  of  the  lymph  (which  will 
be  considered  in  the  next  chapter),  even  although  recent  researches 
throw  grave  doubt  on  the  common  view  that  these  sacs  are  merely 
expanded  lymph  spaces,  and  indicate  that  the  liquid  found  in  them 
has  a  different  origin  from  lymph 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTA.\CES        435 


Section  III. — Absorption  of  the  Various  Food  Substances. 

Absorption  of  Fat — How  the  Fat  gets  into  the  Intestinal  Epithelium. 
— It  has  been  already  mentioned  tliat  fat  is  split  up  in  the  intestine 
into  the  corresponding  alcohols  (mostly  glycerin)  and  fatty  acids, 
but  it  has  been  a  subject  of  discussion  whether  it  all  undergoes  this 
change  or  only  a  portion  of  it.  The  common  view  has  long  been 
that  the  greater  part  of  the  fat  escapes  decomposition,  and,  after 
emulsification  by  the  soaps  formed  from  the  liberated  fatty  acids, 
is  absorbed  as  neutral  fat  by  the  epithelial  cells  covering  the  villi.  If 
an  animal  is  killed  during  digestion  of  a  fatty  meal,  these  cells  are 
found  to  contain  globules  of  different  sizes,  which  stain  black  with 
osmic  acid,  are  dissolved  out  by  ether,  leaving  vacuoles  in  the  cell 
substance,  and  are  therefore  fat  (Fig.  172).  It  has  always  been 
difficult  to  explain  how  droplets  of 
emulsified  fat  could  get  into  the 
interior  of  the  epithelial  cells,  al- 
though, perhaps,  no  more  difficult 
than  to  explain  the  passage  of  living 
tubercle  bacilli  from  the  contents  of 
the  intestine  into  the  chyle  of  the 
thoracic  duct — a  fact  which  has  been 
clearly  demonstrated  (Ravenel).  The 
fat  is  certainly  contained  within  the 
cells,  and  not  between  them.  When 
fat  is  found  in  the  cement  sub- 
stance between  the  cells,  it  has  been 
mechanically  squeezed  out  of  them 
by  the  shrinking  of  the  villi  in 
preparation.  This  difficulty  is  obviated  if  we  suppose  that  the 
whole  of  the  fat  is  split  up  in  the  intestine,  the  products  being 
absorbed  in  solution,  the  glycerin  as  such,  and  the  fatty  acids  either 
as  soaps  or  in  the  free  state,  or  partly  free  and  partly  saponified. 
If  this  is  the  true  theory — and  the  evidence  of  its  truth  has  of  late 
years  been  continually  growing — neutral  fat  must  again  be  built 
up  in  the  epithelial  cells  from  the  absorbed  glycerin  and  the  fatty 
acids  or  soaps.  Now,  it  has  been  shown  that  when  an  animal  is  fed 
with  fatty  acids  they  are  not  only  absorbed,  but  appear  as  neutral 
fats  in  the  chyle  of  the  thoracic  duct,  ha-vang  combined  with  glycerin 
in  the  intestinal  wall;  and  the  epithelial  cells  contain  globules  of 
fat,  just  as  they  do  when  the  animal  is  fed  with  neutral  fat.  Further, 
it  is  known  that  fat-splitting  goes  on  in  the  alimentary  canal  to  a 
much  greater  extent  than  would  be  necessary  merely  for  the  forma- 
tion of  a  quantity  of  soap  sufficient  to  emulsify  the  whole  of  the  fat 
in  the  food.     Indeed,  at  certain  stages  of  digestion  most  of  the 


Fig.  172. — Mucous  Membrane  of 
Frog's  Intestine  during  Absorp- 
tion of  Fat  (Schafer).  ep,  epithe- 
lial cells;  str.  striated  border; 
C,  lymph  corpuscles;  /,  lacteal. 


436  ABSORPTION 

fatty  material,  both  in  the  small  and  large  intestine,  has  been  found 
to  consist  of  fatty  acids.  The  reversibility  of  the  reaction  under 
the  influence  of  lipase,  which  has  already  been  alluded  to,  does  not 
enter  into  the  question  so  far  as  fat-splitting  in  the  intestine  is  con- 
cerned, for  the  products  of  the  reaction  can  be  absorbed  as  quickly 
as  they  are  formed.  To  clinch  the  matter,  it  has  been  proved  that 
when  mixtures  of  paraffin  and  fat,  which  can  be  emulsified  in  a 
watery  solution  of  sodium  carbonate,  are  eaten,  the  paraffin  is  com- 
pletely excreted  with  the  faeces,  while  the  greater  part  of  the  fat  is 
absorijed.  And  fatty  substances  which  are  not  easily  split  up  and 
saponified  (for  example,  lanolin,  the  fat  of  sheep's  wool,  a  mixture 
of  compounds  of  fatty  acids  with  isocholesterin,  a  substance  closely 
related  to  cholesterin  and  allied  bodies)  are  not  absorbed  even  when 
they  are  easily  emulsified.  Even  fats  with  a  melting-point  far 
above  the  temperature  of  the  body  can  be  absorbed  after  being  split 
up.  The  palmitate  of  cetyl  alcohol,  the  chief  constituent  of  sper- 
maceti, melting  at  53°  C,  was  absorbed  to  the  extent  of  15  per 
cent.,  85  per  cent,  being  excreted  in  the  faeces.  It  appeared  as 
palmitiu  in  the  chyle  of  a  human  being  flowing  from  a  fistula,  the 
palmitic  acid  having  been  absorbed  as  such,  or  as  a  sodium  soap,  and 
having  then  united  with  glycerin  to  form  the  neutral  fat,  palmitin. 

Some  observers  have  endeavoured  to  show  that  the  fat  is  absorbed 
without  change  by  introducing  into  the  intestine  fat  stained  with 
dyes,  such  as  alkanna  red  or  Sudan  III.,  which  are  insoluble  in 
water.  The  stained  fat  was  found  in  the  epithelial  cells  of  the  villi, 
in  the  lacteals,  and,  in  the  case  of  a  patient  suffering  from  chyluria, 
in  the  urine.  But  this  evidence  is  not  conclusive,  for  it  has  been 
shown  that  the  pigments  might  easily  have  been  absorbed  after 
decomposition  of  the  fat,  since,  although  insoluble  in  water,  they  are 
soluble  in  fatty  acids,  and  therefore  to  some  extent  in  the  intestinal 
contents,  and  readily  pass  into  the  lymph. 

As  already  pointed  out,  the  bile  plays  an  important  part  in  the 
solution  of  the  fatty  acids,  which  may  form  loose  compounds  with 
the  amide  group  of  the  bile-acids.  In  these  loose  combinations, 
soluble  in  water,  the  fatty  acids  can  be  absorbed  from  the  intestinal 
contents  (Pfliiger).  In  whatever  way  the  fat  which  can  be  seen 
in  the  epithelial  cells  during  absorption  of  fat  gets  into  them,  it 
must  be  carefully  noted  that  there  is  no  quantitative  proof  that  it 
represents  all  or  even  the  greater  part  of  the  absorbed  fat.  So  far 
as  microscopic  observations  go,  much  of  the  fat  may  pass  through 
the  mucosa  in  the  form  of  soluble  decomposition  products  without 
appearing  in  particulate  form  in  the  epithelium. 

How  the  Fat  gets  out  of  the  Intestinal  Epithelium. — Leucocytes 
have  been  asserted  to  be  active  agents  in  the  absorption  of  fat. 
They  have  been  described  as  pushing  their  way  between  the 
epithelial  cells,  fishing,  as  it  were,  for  fatty  particles  in  the  juices 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       437 

of  the  intestine,  and  then  travelling  back  to  discharge  their  cargo 
into  the  lymph.  This  view,  however,  is  erroneous.  But,  although 
the  leucocytes  do  not  aid  in  the  absorption  of  fat  from  the  intestine, 
they  may  take  up  a  certain  amount  of  it  from  the  epithelial  cells, 
and  convey  it  through  the  spaces  of  the  network  of  adenoid  tissue 
that  occupies  the  interior  of  the  villus,  to  discharge  it  into  the 
central  lacteal,  where  it  mingles  with  the  lymph  and  forms  the  so- 
called  molecular  basis  of  the  chyle.  It  has  been  supposed  that  a 
part  of  the  fat  may  reach  the  lacteal  in  another  way.  The  con- 
traction of  the  smooth  muscular  fibres  of  the  villus  and  the  peristaltic 
movements  of  the  intestinal  walls,  which  alter  the  shape  of  the 
villi,  alter  as  well  the  capacity  of  the  lacteal  chamber,  and  so 
alternately  fill  it  from  the  lymph  of  the  adenoid  reticulum,  and 
empty  it  into  the  lymphatic  vessel  with  which  it  is  connected.  By 
this  kind  of  pumping  action  the  passage  of  fat  and  other  substances 
into  the  lymphatics  may  be  aided.  There  is,  however,  no  proof 
that  all  the  fat  accumulated  in  the  intestinal  epithelium  leaves 
it  without  further  change.  It  is  quite  as  probable  that  the  lipase 
which  is  kno^\^l  to  be  contained  in  the  cells  again  hydrolyses  the 
fat,  or  a  portion  of  it,  and  that  the  constituents  then  pass  out  into 
the  lymph,  or  even  in  part  into  the  blood.  In  the  dog  most  of  the 
fat  goes  into  the  lacteals,  and  thence  by  the  general  lymph-stream 
through  the  thoracic  duct  into  the  blood.  And  in  man  the  ch3^1e 
collected  from  a  lymphatic  fistula  contained  a  large  proportion  of 
the  fat  given  in  the  food  (Munk).  But  this  bare  statement  would 
be  misleading  if  we  did  not  add  that  the  fat  taken  in  can  never  be 
entirely  recovered  in  the  chyle  collected  from  the  thoracic  duct. 
A  small  fraction  of  the  deficit  might  be  accounted  for  as  fat  directly 
used  up  for  the  nutrition  of  the  intestinal  wall  itself.  But  even  after 
ligation  of  the  thoracic  and  right  lymphatic  ducts  a  large  proportion 
of  a  meal  of  fat  (32  to  48  per  cent.)  is  absorbed  from  the  intestine, 
obviously  by  the  channel  of  the  bloodvessels,  since  the  fat-content 
of  the  blood  increases  up  to,  it  may  be,  six  times  the  highest  amount 
present  in  the  blood  of  fasting  animals.  The  statement  that  only 
fatty  acids  can  be  absorbed  under  these  conditions  is  erroneous 
(Munk  and  Friedenthal). 

A  dog  normally  absorbs  9  to  21  per  cent,  of  the  fat  in  a  meal  in 
three  to  four  hours;  21  to  46  per  cent,  in  seven  hours;  and  86  per 
cent,  in  eighteen  hours  (Harley).  After  excision  of  the  pancreas 
the  absorption  of  fat  is  hindered,  though  not  abolished.  More  fat, 
indeed,  can  be  recovered  from  the  intestine  than  is  given  in  the  food. 
This  at  first  sight  paradoxical  result  is  explained  by  the  well-estab- 
lished fact  that  a  certain  amount  of  fat  is  normally  excreted  into 
the  intestine. 

Mechanism  of  Fat  Synthesis  in  the  Intestinal  Mucosa. — As  to  the 
manner  in  which  the  synthesis  of  the  fat  in  the  intestinal  epithehum 


438  ABSORPTION 

is  accomplished,  the  most  fascinating  theory  is  that  which  attributes 
it  to  the  reversed  action  of  hpase,  possibly  the  very  same  lipase  as 
originally  split  it  up  in  the  intestine.  The  reversibility  of  the  action 
of  various  enzymes  under  changed  conditions,  especiall3^  changes  in 
the  relative  concentration  of  the  bodies  concerned  in  the  reaction, 
has  been  previously  mentioned.  It  has  been  shown,  e.g.,  that  the 
pancreas,  intestinal  mucous  membrane,  lymph  glands,  etc.,  and 
even  cell-free  extracts  of  these  organs  have  the  power  of  synthesizing 
the  ester  ethyl  butyrate  from  butyric  acid  and  ethyl  alcohol 
(p.  332),  as  well  as  the  power  of  decomposing  the  ester  into  the 
fatty  acid  and  the  alcohol.  Moore,  however,  states  that  in  the 
case  of  ordinary  fats  the  synthesis  takes  place  in  the  intestinal  wall 
only  in  situ,  and  while  the  circulation  is  going  on.  In  the  intestinal 
mucosa  the  greater  part  of  the  fatty  acid  is  already  combined  with 
glycerin  as  neutral  fat,  although  considerable  quantities  of  free  fatty 
acid  are  also  present.  In  the  lymph  coming  directly  from  the 
mesenteric  glands  practically  the  whole  of  the  fatty  acids  are  in 
the  form  of  neutral  fat. 

An  additional,  and  in  some  respects  even  more  remarkable,  illus- 
tration of  the  synthesizing  powers  of  the  intestinal  wall  is  the  dis- 
covery of  Munk,  already  referred  to  (p.  433),  that  fatty  acids  given 
by  the  mouth  appear  in  the  lymph  of  the  thoracic  duct  as  neutral 
fats,  having  somewhere  or  other,  in  all  probability  on  their  way 
through  the  epithelium  of  the  gut,  been  combined  with  glycerin. 

Since,  however,  the  amount  of  neutral  fat  recovered  from  the 
thoracic  duct  is  not  equivalent  to  more  than  one-third  of  the  fatty 
acids  given,  it  has  been  suggested  that  this  synthesis  of  fat  is  only 
apparent,  and  that  the  whole  of  the  fat  which  appears  in  the  chyle 
after  a  meal  of  fatty  acids  comes  from  the  fat  excreted  into  the 
intestine  (Frank),  which  is  increased  when  fatty  acids  are  given  by 
the  mouth.  But  the  suggestion  is  more  ingenious  than  the  evidence 
advanced  in  its  support  is  convincing.  And,  as  we  have  seen 
(p.  437),  a  part  of  the  deficit  may  be  accounted  for  by  absorption 
directly  into  the  bloodvessels. 

In  concluding  our  review  of  the  absorption  of  fat,  certain  general 
considerations  which  have  a  close  relation  to  the  question  may  be 
alluded  to.  There  is  some  reason  to  think  that  the  lipases  are 
enzymes  less  finely  adjusted  to  minute  differences  in  the  structure 
of  the  fats  on  which  they  act  than  other  digestive  ferments — e.g., 
maltase  or  lactase,  to  details  in  the  chemical  structure  of  their 
substrates.  If  this  be  so,  a  very  few  lipases,  or  even  a  single  one, 
may  suffice  to  accomplish  all  the  enzymatic  changes  which  occur 
in  the  fats  both  in  the  lumen  of  the  intestine  and  in  all  the  various 
tissue  cells.  At  the  same  time  the  possible  variation  in  those  decom- 
position products  which  constitute  the  '  building-stones  '  of  the  fats 
is  less  than  in  the  case  of,  say,  the  proteins.     Two  consequences 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       439 

follow  as  regards  the  absorption  of  fat :  (i)  Each  cell  may  be  capable 
of  dealing  with  the  original  neutral  fats  of  the  food,  and  of  adapting 
them  to  its  needs  by  decomposing  and  rcsynthesizing  them  so  far 
as  is  necessary  in  its  own  substance.  In  tiiis  case  it  would  not  be 
necessary  for  assimilation  by  the  cells  that  the  fats  should  be  com- 
pletely split  or  even  split  at  all  in  the  alimentary  canal,  however 
important  this  might  be  for  their  absorption  from  its  lumen. 
(2)  If  it  were  necessary  for  absorption  that  decomposition  of  the 
fats  should  take  place  in  the  lumen  of  the  digestive  tube,  the  whole 
of  the  fat,  or  at  any  rate  sucli  portion  of  it  as  was  not  at  once  needed, 
might  without  disadvantage  for  the  tissues  be  resynthesized  after 
absorption.  It  is  not  difficult  to  see  that  it  might  even  be  advan- 
tageous that  not  only  the  relatively  fixed  reserve  in  the  fat  cells, 
but  also  what  might  be  termed  the  floating  or  circulating  reserve 
constituted  by  the  emulsified  fat  in  the  blood  should  be  in  the 
insoluble  form  of  neutral  fat. 

Absorption    of    Carbo- Hydrates. — Carbo-hydrates    are  normally 
absorbed  from  the  alimentary  canal  only  in  the  form  of  mono- 
saccharides, such  as  dextrose,  levulose  or  fructose,  and  galactose, 
but    especially    dextrose.      These    monosaccharides    are    readily 
formed  from  polysaccharides  like  starch  and  dextrin,  and  the  disac- 
charide  maltose,  which  they  yield  on  digestion  with  amylase,  as 
well  as  from  disaccharides  like  cane-sugar  and  lactose,  by  the  fer- 
ments already  studied.     That,  as  a  matter  of  fact,  the  hydrolysis 
in  the  intestine  must  convert  practically  all  the  carbo-hydrate  into 
monosaccharides  before  absorption,  can  be  shown  in  various  ways. 
The  ferment  lactase,  while  present  in  the  small  intestine  of  all 
young  mammals,  is  regularly  absent  in  some  mammalian  groups 
in  the  adult.     In  other  species,  including  man,  it  is  found  in  some 
adults,  but  not  in  all.     In  birds  and  other  animals  below  the  mam- 
mals, it  has  not  hitherto  been  found  at  any  age.     It  has  been  sur- 
mised that  these  differences  depend  upon  the  presence  or  absence 
of  lactose  (milk)  as  a  regular  constituent  of  the  food.     (But  see 
p.  404.)     If,  now,  lactose  is  introduced  into  a  loop  of  intestine  in  an 
animal  which  does  not  possess  lactase — e.g.,  an  adult  rabbit — it  is 
not  ajDsorbed,  but  remains  in  the  lumen  till  it  is  at  last  decomposed 
by  bacterial  action.     In  animals  in  which  lactase  is  present  the 
lactose  is  rapidly  absorbed.     Maltose  is  easily  taken  up  from  the 
intestine  because  of  the  action  of  the  ferment  maltase,  which  is  the 
most  widely  spread  of  all  the  inverting  ferments.  The  dextrose  formed 
by  the  maltase  is  so  rapidly  absorbed  that  none,  or  only  traces,  of  it 
can  be  detected  in  the  contents  of  the  intestinal  loop.    But  if  absorp- 
tion be  interfered  with  by  injuring  the  intestine,  maltose  disappears, 
and  the  dextrose  produced  from  it  accumulates  in  the  lumen.   The 
reason  for  the  discrimination  exercised  by  the  intestinal  mucosa  in 
favour  of  the  monosaccharides  becomes  apparent  when  an  attempt  is 


440  ABSORPTION 

made  to  circumvent  it  by  injecting  the  sugars  parenterally — i.e.,  into 
subcutaneous  or  intramuscular  connective  tissue,  into  a  serous  sac, 
or  directly  into  the  blood.  Cane-sugar  and  lactose  so  introduced 
are  excreted  unchanged  in  the  urine.  Dextrose,  levulose,  and 
galactose  are  used  up  in  the  body,  and  some  maltose  hkewise, 
thanks  to  the  presence  of  maltase  in  the  blood  and  tissues.  The  cells 
of  the  body  in  general  will  burn  only  monosaccharides,  and  not  di-  or 
poly-saccharides.  Galactose  and  fructose  are  probably  first  con- 
verted into  dextrose  before  being  utilized  by  the  tissues,  a  change 
which  can  also  be  readily  induced  in  the  test-tube.  Therefore  the 
intestine  admits  the  simple,  but  rejects  the  more  complex  sugars. 
It  is  only  in  the  presence  of  abnormally  great  quantities  or  ab- 
normally great  concentrations  of  the  sugars  which  are  not  directly 
utilizable  that  they  are  to  a  certain  extent  taken  up  unaltered, 
to  be  for  the  most  part  quickly  excreted  as  such  (p.  532).  In  like 
manner  we  have  seen  that  the  native  proteins  can,  so  to  speak, 
force  their  way  by  storm  through  the  intestinal  mucosa  when 
offered  to  it  in  exceptionally  large  amount.  The  sugar  absorbed 
from  the  intestine  passes  normally  into  the  rootlets  of  the  portal  vein, 
not  into  the  chyle,  for  no  increase  in  the  quantity  of  that  substance 
in  the  contents  of  the  thoracic  duct  takes  place  during  digestion, 
while  the  sugar  in  the  portal  blood  is  increased  after  a  starchy  meal. 
The  blood  of  the  portal  vein  of  a  dog  in  the  fasting  condition  con- 
tained 0-2  per  cent,  of  dextrose.  During  absorption  of  a  meal  rich. 
ii  carbo-hydrates  it  contained  as  much  as  0*4  per  cent.  In  the 
lymph  issuing  from  the  thoracic  duct  the  amount  was  the  same  in 
both  conditions — viz.,  o-i6  per  cent.  In  a  case  of  lymph  (chyle) 
fistula  in  a  human  being,  where  almost  all  the  lymph  from  the 
digestive  tract  esciped  through  the  fistula,  out  of  100  grammes  of 
carbo-hydrate  taken  (50  grammes  starch  and  50  grammes  sugar), 
only  I  granmie,  or  not  i  per  cent,  of  the  sugar  corresponding  to  the 
carbo-hydrates  of  the  food,  could  be  recovered  in  the  chyle.  But 
when  a  large  amount  of  a  dilute  solution  of  sugar  is  introduced  into 
the  intestine,  some  of  it  is  taken  up  by  the  lacteals. 

Absorption  of  Water  and  Salts. — The  main  channel  for  absorption 
of  these  is  the  bloodvessels  of  the  intestine.  As  much  as  3  to  5  litres 
of  water  can  be  absorbed  in  a  day  in  the  intestine  of  a  healthy  man, 
exceptionally  even  6  to  10  litres,  without  the  fseces  altering  their 
normal  consistence.  Absorption  of  the  water  and  dissolved  salts 
may  theoretically  take  place  either  through  the  epithelial  cells  (intra- 
epithelial absorption),  or  between  the  cells  (interepithelial  absorp- 
tion). According  to  Hober,  most  metallic  salts  (silver,  mercury, 
lead,  bismuth,  copper,  manganese,  etc.)  are  absorbed  interepitheli- 
ally,  while  iron  salts  form  an  exception,  and  pass  into  the  epithelial 
cells.  The  distinction  between  interepithelial  and  intra-epithelial 
absorption  does  not  rest  upon  an  absolutely  sure  foundation.     Yet 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       441 

it  is  probable  that  everything  which  is  useful  in  the  nutrition  of 
the  body  is  taken  up  by  the  cells,  while  such  substances  as  metalhc 
salts  which  are  foreign  to  the  organism,  and  are  denied  entrance 
into  the  cells,  may  pass  in  small  amount  between  them,  their  passage 
being  perhaps  associated  with  more  or  less  injury  to  the  interstitial 
substance.  The  vigilant  selection  exercised  by  the  mucosa  is  well 
illustrated  by  the  facts  that,  although  manganese  and  iron  are 
chemically  so  closely  related,  iron,  which  is  necessary  for  the 
formation  of  the  blood-pigment,  is  absorbed  in  immensely  greater 
amount  than  manganese;  and  that  chlorides,  especially  sodium 
chloride,  are  readily  taken  up,  sulphates  with  difficulty.  Iron  is 
absorbed  by  the  bloodvessels,  but  also  to  some  extent  by  the  lacteals. 
From  the  blood  it  is  carried  to  various  organs,  especially  the  spleen 
and  liver.  There  is  reason  to  believe  that  the  eosinophile  leucocytes 
take  some  share  in  its  transportation. 

It  was  supposed  by  Bunge  that  only  organic  compounds  of  iron 
could  be  absorbed,  and  that  the  undoubted  benefit  derived  from 
the  administration  of  inorganic  iron  compounds,  such  as  ferric 
chloride,  in  chlorosis,  was  due  not  to  their  direct  absorption,  but 
to  their  shielding  the  organic  compounds  from  the  attack  of  the 
sulphuretted  hydrogen  in  the  intestine  (p.  419).  But  this  theory 
has  been  shown  to  be  inconsistent  with  the  facts.  For  instance, 
after  the  administration  of  salts  of  iron,  the  iron  in  the  blood, 
liver,  spleen,  and  other  organs  increases,  but  there  is  no  accumula- 
tion of  iron  in  the  liver  of  an  animal  to  which  salts  of  manganese 
have  been  given,  although  these  are  equally  decomposed  by  sul- 
phuretted hydrogen. 

Absorption  of  Proteins. — The  proteins  of  the  food  or  their  digested 
products  also  pass  directly  into  the  blood-capillaries  which  feed 
the  portal  system.  For  it  has  been  shown  that  after  ligature  of 
the  thoracic  duct  protein  substances  are  still  absorbed  from  the 
intestine,  and  the  urea  corresponding  to  their  nitrogen  appears  in 
the  urine.  The  total  nitrogen  in  the  chyle  flowing  from  a  fistula 
of  the  thoracic  duct  in  a  man  was  not  found  to  be  increased  during 
the  digestion  of  protein  food.  The  quantity  of  chyle  escaping  in  a 
given  time  was  also  unaffected,  whereas  during  the  digestion  of  fats 
it  was  greatly  augmented  (Munk)' 

Although  a  certain  amount  of  egg-albumin,  serum-albumin,  alkali- 
albumin,  and  other  native  or  slightly  altered  protein  substances 
can  be  absorbed  as  such  by  the  small,  and  even  by  the  large,  in- 
testine, there  is  no  evidence  that,  under  ordinary  conditions,  this 
mode  of  absorption  is  of  any  practical  importance  in  nutrition, 
although  in  another  relation  it  may  possess  a  certain  interest  (p.  32). 
For  when  native  proteins,  with  the  possible  exception  of  the 
serum  proteins  from  an  animal  of  the  same  species,  are  introduced 
'  parenterally, '  so  that  they  do  not  reach  the  tissues  by  way  of 


442  ABSORPTION 

the  alimentary  canal,  they  behave  in  a  very  different  manner  from 
the  same  proteins  when  given  by  the  mouth.  One  notable  differ- 
ence is  that  the  parenterally  administered  proteins  give  rise  in 
general  to  the  formation  of  antibodies — e.g.,  specific  precipitins 
(p.  31).  This  is  not  the  case  when  they  are  administered  per  os, 
unless,  like  raw  egg-white,  which,  as  already  mentioned  (p.  398), 
evokes  no  secretion  of  gastric  juice,  they  remain  long  undigested 
in  the  alimentary  canal,  when  an  amount  sufficient  to  cause  the 
production  of  precipitins  may  eventually  be  absorbed  unaltered. 
This  has  also  been  shown  by  means  of  the  anaphylactic  reaction. 
Secondly,  they  are  not,  as  a  rule,  utilized  in  the  metabolism  of  the 
body,  or  are  utilized  very  incompletely.  Egg-albumin,  for  instance, 
when  injected  into  the  blood,  is  excreted  in  the  urine.  It  has  been 
previously  pointed  out  that  the  various  proteins  differ  remarkably 
not  so  much  in  the  kinds  as  in  the  relative  quantities  of  the  amino- 
and  diamino-acids  which  can  be  obtained  from  them  (p.  2).  This 
is  unquestionably  one  important  reason  why  the  food  proteins  are — 
for  the  most  part,  at  any  rate — so  thoroughly  hydrolysed  before 
absorption.  Another  may  be  that  it  is  easier  for  the  intestine  to 
take  up  the  small  molecules  of  the  decomposition  products  than 
the  large  colloid  aggregates  of  the  original  protein  solutions. 

So  far  as  the  first  reason  is  concerned,  the  degree  of  decomposi- 
tion need  not  be  the  same  for  all  the  food  proteins,  although  all 
muat  be  decomposed,  for  even  among  the  proteins  the  products  of 
whose  hydrolysis  do  not  exhibit  qualitative  differences,  no  two 
have  hitherto  been  discovered  which  show  the  same  quantitative 
relations  among  the  '  building-stones. '  A  new  house  has  to  be  built 
fiom  the  materials  of  an  old  one.  How  far  the  work  of  demolition 
must  be  carried  will  depend  upon  the  difference  between  the  plans 
of  the  two  houses.  Sometimes  the  main  part  of  the  old  building 
may  be  saved,  and  only  the  wings  require  reconstruction.  In  like 
manner  it  is  conceivable  that  the  central  group  or  nucleus  of  the 
molecule  of  a  given  food  protein  may  be  identical  with  that  of  a 
given  body  protein,  and  that  only  the  side-chains  maybe  so  different 
that  they  must  be  broken  up  and  reconstructed.  Or,  again,  the 
whole  architectural  plan  of  the  new  house  may  be  so  distinct  from 
that  of  the  old  that  the  only  feasible  method  is  to  completely 
demolish  the  latter,  and  then  to  use  the  individual  bricks  in  the 
new  construction;  just  as  a  protein  in  the  food  may  differ  so 
radically  "from  a  tissue  protein  into  which  it  is  to  be  transformed 
that  it  must  be  decomposed  into  the  simplest  products  of  proteo- 
lysis before  the  reconstruction  of  the  molecule  can  begin.  It  is  not 
known  what  the  minimum  degree  of  hydrolysis  is  which  will  permit 
of  effective  absorption  and  utilization.  But  it  would  seem  that  it 
must  be  very  complete.  Even  a  body  so  simple  in  comparison  with 
the   proteins   as  the  tripeptide  (p.    2)  alanyl-glycyl-tyrosin,  con- 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       443 

taining  only  three  '  building-stones/  can  only  be  changed  into  the 
tripeptidc  alanyl-tyrosyl-glycin  by  first  hydrolysing  it  into  its  three 
components  and  then  synthesizing  these  afresh.  On  the  other 
hand,  in  obtaining  the  tripeptide  glycyl-tyrosyl-alanin  from  alanyl- 
glycyl-tyrosin,  the  dipeptide  group  glycyl-tjTosin  can  remain  un- 
decomposed,  and  it  is  only  necessary  to  split  alanin  off  and  link  it 
up  to  the  dipeptide  to  obtain  the  desired  glycyl-tyrosyl-alanin 
(Abdcrhalden).  There  can  be  no  doubt  that  by  far  the  greater 
part,  if  not  the  whole,  of  the  proteins  of  the  food  is  first  changed  into 
proteoses  and  peptones.  But  proteose  and  peptone  are  absent 
from  the  blood,  and,  indeed,  when  injected  into  the  blood  they 
are  excreted  in  the  urine.  When  injected  in  larger  amount,  they 
pass  also  into  the  lymph,  from  which  they  gradually  reach  the  blood 
again,  and  are  eventually,  as  before,  eliminated  by  the  kidneys. 
The  clear  inference  is  that  if  they  are  absorbed  as  such  from  the 
alimentary  canal,  they  must  be  changed  in  their  passage  through  its 
walls.  The  fact  that  a  portion  at  any  rate  of  the  peptones  and 
proteoses  is  decomposed  into  amino-acids,  etc.,  in  the  lumen 
of  the  intestine  has  been  already  alluded  to.  It  is  certain  that 
this  portion  is  a  very  large  proportion  of  the  whole,  although  the 
question  how  much,  if  any,  of  the  peptone  passes  as  such  from  the 
lumen  into  the  mucosa  must  still  be  left  undecided.  It  is  true 
that  along  with  amino-acids  peptones  are  always  found  in  the 
intestine  during  the  digestion  of  protein,  and  the  quantity  of 
amino-acids  actually  present  in  the  lumen  at  any  moment  may 
be  small  in  proportion  to  the  quantity  of  peptone.  But  this  is 
precisely  what  is  to  be  expected  if  the  peptone  as  such  is  incapable 
of  absorption.  For  the  easily  absorbed  amino-acids  will  disappear 
from  the  gut  as  fast  as  they  are  formed,  leaving  behind  the  peptone 
for  further  hydrolysis.  The  fact  that  all  the  amino-acids  which  the 
proteins  are  capable  of  yielding  can  be  detected  in  the  contents  of 
the  intestine,  including  even  those  which  appear  late  and,  as  it 
were,  reluctantly  in  artificial  digestion,  is  a  proof  that  the  decom- 
position of  the  protein  goes  fast  and  far  in  the  alimentary  canal. 
If  it  is  not  complete,  if  some  of  the  partially  hydrolysed  protein  is 
taken  up  by  the  mucous  membrane  in  the  form  of  peptones  or 
possibly  even  of  proteoses,  it  would  seem  that  this  is  similarly 
decomposed  by  the  action  of  erepsin  in  the  intestinal  wall. 

It  has  been  stated  that  during  the  digestion  of  a  protein  meal  the 
mucosa  of  the  stomach  and  intestine  contains  proteose  and  pep- 
tone, while  none  is  present  in  the  muscular  coat  or  in  any  other 
organ.  They  rapidly  disappear  from  a  portion  of  the  mucous  mem- 
brane kept  at  a  temperature  of  about  40°  C.  outside  of  the  body,  and 
their  disappearance  is  due,  not  to  their  regeneration  into  serum 
proteins,  as  was  once  supposed,  but  to  their  decomposition  by  the 
erepsin.     We  must  suppose  that  the  serum  and  organ  proteins  are 


444  ABSORPTION 

built  up  from  the  products  of  this  decomposition.  But  whether  the 
mucosa  of  the  ahmentary  tract  is  especially  a  seat  of  the  synthesis 
is  unknown  (p.  564).  On  a  priori  grounds,  it  is  at  least  equally 
probable  that  it  occurs  in  all  the  cells  of  the  body,  each  one  building 
up  for  itself  the  particular  kind  of  protein  which  it  needs.  The 
direct  way  of  testing  the  question  would  be  to  examine  the  blood 
coming  from  the  intestine  during  the  absorption  of  proteins,  and  to 
determine  quantitatively  any  changes  which  might  have  occurred  in 
the  nitrogenous  constituents.  But  the  flow  of  blood  through  the 
intestine  is  so  great,  the  absorption  of  the  digestive  products  so 
gradual,  and  their  removal  from  the  blood  by  the  tissues,  in  all 
probability,  so  rapid,  that  there  is  no  reason  for  surprise  that  till 
lately  the  results  of  such  determinations  were  ambiguous.  Leathes, 
however,  showed  some  time  ago  that  when  peptone,  proteose,  or  the 
final  products  of  tryptic  digestion  are  introduced  into  a  ligated 
segment  of  a  dog's  small  intestine,  there  is  always,  when  absorption 
occurs,  an  increase  in  the  nitrogenous  substances  in  the  blood,  in  the 
form  of  compounds  which  are  not  precipitated  by  tannic  acid,  and 
therefore  are  neither  native  proteins  nor  proteose.  Urea  accounts 
for  about  one-half  of  the  increase ;  the  rest  he  considered  to  represent 
probably  amino-acids  and  similar  substances.  Quite  recently  it 
has  been  conclusively  demonstrated  by  improved  methods  that  the 
digestion  of  protein  is  associated  with  an  increase  of  non-protein 
nitrogen  in  the  blood,  due,  there  is  every  reason  to  believe,  to  amino- 
bodies  derived  from  the  hydrolysed  protein  (Folin  and  Denis,  Van 
Slyke,  Abel).  This  proves  for  the  mammal  what  had  been  deduced 
by  Cohnheim  for  a  much  lower  form  from  experiments  made  on  the 
intestines  of  certain  octopods,  which,  when  excised  and  suspended 
in  the  oxygenated  blood,  will  live  for  many  hours.  A  solution  of 
peptone  was  introduced  into  the  isolated  intestine,  and  after  twenty 
hours  the  crystalline  products,  leucin,  tyrosin,  lysin,  and  arginin, 
were  found  in  the  blood.  In  the  intact  animal  none  of  these  bodies 
could  be  detected  in  the  blood  (Cohnheim).  The  inference  was 
that  protein  in  these  animals  is  absorbed  in  the  form  of  amino-acids, 
etc.,  which  are  then  carried  to  the  tissues  and  utilized  there.  In 
the  mammal  the  same  thing  appears  to  be  true.  For  the  increase 
in  the  amino-acids  during  digestion  of  proteins  occurs  not  only  in 
the  portal  blood,  but  in  the  blood  of  the  general  circulation.  So 
that,  although  a  part  of  the  absorbed  amino-bodies  may  be  removed 
by  the  liver,  a  portion  at  least  is  available  for  the  tissues  in  general. 
That  the  tissues  actually  take  up  such  decomposition  products  of 
proteins  is  indicated  by  the  fact  that  during  and  after  the  digestion 
of  protein  in  a  loop  of  intestine  the  non-protein  nitrogen  of  the 
tissues  is  increased  (Folin).  It  may  be  that  some  of  the  proteose 
and  peptone  are  regenerated  by  a  shorter  process,  and  without 
having  been  further  split  up,  but  of  this,  too,  there  is  no  definite 


ABSORPTION  OF  THE   VARIOUS  FOOD  SUBSTANCES       445 

proof.  The  regeneration,  wherever  it  occurs,  must  presumably  take 
place  in  cells,  and  the  only  available  cells  in  the  digestive  mucous 
membrane  are  those  which  hne  the  tube,  or  the  leucocytes  which 
wander  between  them.  Accordingly,  both  have  been  credited  with 
the  power  of  absorbing  (and  perhaps  transforming)  these  substances, 
but  the  balance  of  evidence  is  in  favour  of  the  epithelial  cells.  We 
cannot,  however,  as  in  the  case  of  the  fat,  single  out  any  particular 
tract  of  epithehum  as  alone  engaged  in  the  absorption  (and  possibly 
in  the  resynthesis)  of  the  products  of  the  digestion  of  the  proteins. 
In  all  likelihood  the  cells  covering  the  villi  are  actively  concerned, 
but  there  is  no  valid  reason  for  denying  a  share  to  the  general  lining 
of  the  stomach  and  small  intestine,  even  perhaps  including  the 
Lieberkiihn's  crypts  or  intestinal  glands,  which  morphologically 
form  a  kind  of  inverted  villi.  It  is,  indeed,  true  that  the  crypts 
do  not  take  part  in  the  absorption  of  fat,  for  no  granules  blackened 
by  osmic  acid  occur  in  them  during  digestion  of  a  fatty  meal.  But 
this  is  a  ground  for  attributing  to  them  other  absorptive  functions 
rather  than  for  altogether  denying  to  them  a  share  in  absorption, 
unless,  indeed,  we  assume  that  the  secretion  of  the  succus  entericus 
engrosses  the  whole  activity  of  this  extensive  sheet  of  cells.  Ev^en 
within  physiological  limits  distension  of  the  gut  causes  the  crypts 
to  become  shorter  and  broader,  by  a  process  of  partial  unfolding 
which  permits  a  greater  part  of  their  epithehum  to  come  into  con- 
tact with  the  intestinal  contents.  In  extreme  distension  they  may 
be  completely  smoothed  out. 

The  extraordinary  efficiency  of  the;  small  intestine  in  digestion 
and  absorption  is  shown  by  the  fact  that,  after  removal  of  even 
70  to  83  per  cent,  of  the  combined  jejunum  and  ileum  in  dogs,  the 
metabolism  is  not  necessarily  much  affected.  On  a  diet  poor  in 
fat  the  animals  absorb  as  much  of  the  fat  as  a  normal  dog,  although 
a  smaller  proportion  when  the  diet  is  rich  in  fat.  It  has  been 
generally  stated  that  it  is  never  permissible  to  remove  more  than 
one-third  of  the  small  intestine  in  man.  But  in  one  case  2|  metres 
was  resected,  or  quite  one-half,  and  the  patient  recovered.  Even 
the  large  intestine,  which  possesses  Lieberkiihn's  crypts,  but  no  villi, 
is  able  to  absorb  not  only  peptones  and  sugar,  especially  mono- 
saccharides like  dextrose,  but  also  fats  and  native  proteins.  And 
although  these  are  powers  which  can  be  rarely  exercised  to  any  great 
extent  in  normal  digestion,  they  form  the  physiological  basis  of  the 
important  method  of  treatment  by  nutrient  enemata.  The  observa- 
tion already  mentioned  (p.  325),  that  considerable  quantities  of 
food  administered  by  the  rectum  can  pass  through  the  ileo-colic 
sphincter  and  valve  into  the  lower  part  of  the  ileum,  thanks  to  the 
antiperistaltic  movements  of  the  large  intestine,  indicates  that  an 
important  part  of  the  preliminary  digestion  and  of  the  absorption 
of  enemata  may  occur  in  the  small  intestine.     But  remnants  of  the 


446  ABSORPTION 

proteolytic,  amylolytic,  fat-splitting,  and  inverting  ferments  which 
have  done  their  work  in  the  small  intestine  are  passed  on  into  the 
large,  and  may  be  demonstrated  in  its  contents.  Doubtless  these 
are  able  to  act  upon  food  substances  which  may  have  escaped  com- 
plete digestion  and  absorption  in  the  higher  parts  of  the  alimentary 
canal,  as  well  as  upon  food  substances  injected  into  the  rectum. 

Summary. — With  the  proviso  that  in  the  case  of  the  fats  the 
statement  may  in  the  present  condition  of  our  knowledge  be  some- 
what '  diagrammatic,'  we  may  sum  up  in  a  few  words  the  chief 
points  in  the  absorption  of  the  food  materials.  All  the  fats  must  be 
split  in  order  to  be  absorbed  in  soluble  form  from  the  intestine,  but 
need  not  be  split  in  the  lumen  of  the  gut  in  order  to  be  utilized  by  the 
cells.  For  this  reason  they  are  to  a  great  extent  resynthesized  to 
neutral  fat  after  absorption,  and  find  their  way  into  the  blood,  mainly 
by  way  of  the  lymph,  in  particulate  form.  Proteins  could  perhaps  to 
a  small  extent  be  absorbed  as  such,  but  must  be  thoroughly  hydrolysed 
in  order  to  be  utilized  by  the  tissues,  and  also  in  order  to  be  freely 
taken  up  from  the  gut.  Carbo-hydrates  in  certain  forms  {mono- 
saccharides) are  capable  without  change  of  being  both  freely  absorbed 
from  the  intestine  and  thoroughly  utilized  by  the  cells  ;  only  the  more 
complex  carbo-hydrates  need  to  be  hydrolysed  in  order  to  be  absorbed, 
but  all  above  the  monosaccharides  must  be  hydrolysed  to  monosac- 
charides in  order  to  be  utilized.  The  substances  ivhich  eventually 
circulate  in  the  blood  in  solution  reach  it  through  the  gastro-intestinal 
capillaries  ;  the  substances  which  eventually  circulate  in  the  blood  in 
particulate  form  reach  it  through  the  lymphatics. 


PRACTICAL  EXERCISES  ON  CHAPTERS  VI.  AND  VII. 

I.  Contraction  of  Isolated  Intestines  in  Ringer's  Solution. — Arrange 
a  good-sized  water-bath  (a  water-tight  garbage-can  holding  20  litres 
will  do)  so  that  the  temperature  of  the  water  is  kept  at  37°  to  38°  C. 
For  this  a  gas  regulator  is  most  convenient,  and  also  a  stirring  arrange- 
ment worked  by  a  small  motor.  But  if  neither  of  these  is  available, 
a  student,  by  a  little  care,  can  easily  keep  the  water  at  the  required 
temperature  by  raising  and  lowering  the  gas  flame  and  stirring  occasion- 
ally by  hand.  In  the  bath,  support  [a)  a  stock  bottle  of  Ringer's 
solution  (footnote,  p.  66),  (6)  a  wide-mouthed  bottle  containing  Ringer 
for  the  reception  of  the  stock  of  intestine,  (c)  a  small  cylinder  for 
segments  of  intestine  whose  contractions  are  to  be  recorded,  (c)  is 
conveniently  made  in  different  sizes  by  cutting  down  glass  T-pieces. 
One  which  holds  4  or  5  c.c.  is  convenient.  The  bottom  is  plugged  with 
a  rubber  cork  in  which  is  fastened  a  hook.  In  the  side-piece  is  fixed 
by  a  rubber  cork  a  glass  tube  ending  in  the  cylinder  in  a  narrow 
orifice.  This  is  connected  with  tlie  oxygen-supply,  conveniently  ob- 
tained under  constant  pressure  from  a  small  gas-container  which  is 
periodically  replenished  from  an  oxygen  cylinder.  A  separate  oxygen 
cylinder  is  connected  with  a  tube  passing  to  the  bottom  of  (6).  A  lever 
with  two  arms  is  arranged  on  the  same  stand  as  (c),  so  that  it  can  be 
thrown  on  and  off  a  slow-inoving  drum  by  a  single  movement  of  the  stand. 

All  being  ready,  a  rabbit  is  killed  by  being  struck  on  the  back  of  the 


PRACTICAL  EXERCISES  447 

head.  The  small  intestine  is  immediately  removed.  It  may  be  cut 
between  double  ligatures  into  several  pieces  for  this  purpose.  The 
contents  are  rapidly  washed  out  by  a  stream  of  warm  Ringer,  and 
the  pieces  placed  in  (6),  through  which  oxygen  is  kept  bubbling.  The 
pieces  arc  conveniently  supported  in  the  liquid  by  threads  fixed  by 
the  cork  of  the  bottle.  There  is  a  hole  in  the  cork  for  the  escape  of 
the  oxygen.  The  movements  ol  the  intestines  in  {b)  can  be  studied 
verjMve  11  by  inspection.  Or  a  separate  length  of  intestine  maybe  kept 
for  this  purpose,  the  contents  not  being  removed,  but  prevented  from 
escaping  by  ligatures  at  each  end.  This  can  be  most  easily  ob.served  in  a 
shallow  dish  of  warm  Ringer.  Or  a  separate  experiment  can  be  made 
in  which  the  whole  alimentary  canal  of  a  rabbit  is  carefully  removed 
and  examined  in  oxygenated  Ringer's  solution. 

A  segment  of  intestine  about  2  or  2^  cm.  in  length  is  now  cut  off 
one  of  the  pieces.  A  small  ring  of  platinum  or  aluminium  is  tied  to 
a  point  on  the  circumference  of  one  end  of  the  preparation  by  a  silk 
thread  passed  through  the  wall.  The  other  end  is  caught  by  a  serre- 
fine  at  a  point  exactly  corresponding  to  the  attachment  of  the  ring,  so 
that  the  pull  of  the  contracting  longitudinal  muscle  should  be  in  the 
straight  line  joining  these  two  points.  The  serre-fine  has  attached  to 
it  a  thread  with  a  liook  on  the  other  end.  In  preparing  the  intestinal 
segment  it  lies  on  a  plate  of  glass  above  a  vessel  of  warm  water.  The 
small  cylinder  (c)  is  now  partially  filled  with  warm  Ringer's  solution. 
The  ring  is  grasped  by  fine  forceps,  and  made  to  engage  with  the  hook 
at  the  bottom  of  the  cylinder,  care  being  taken  not  to  injure  the  prepara- 
tion in  the  process.  The  cylinder  is  then  fastened  on  its  stand  and 
lowered  into  the  bath.  The  thread  is  connected  by  its  attached  hook 
to  the  lever,  and  oxygen  allowed  to  bubble  slowly  and  regularly  through 
the  cylinder.  Very  soon  rhythmical  contractions  begin  (Fig.  173),  and 
continue  for  a  long  time.  The  effect  on  these  contractions  of  abolish- 
ing, reducing,  or  increasing  the  oxygen-supply  may  first  be  studied. 

2 .  Effect  of  Blood-Serum  on  the  Contractions  of  Intestinal  Segments. 
— While  a  tracing  is  being  taken  as  in  i,  fill  a  small  bent  pipette  with 
scrum  already  warmed  in  the  bath,  pass  the  point  of  the  pipette  down  to 
the  bottom  of  the  cylinder  without  interfering  with  the  preparation,  and 
allow  the  serum  to  flow  in  till  the  Ringer's  solution  is  displaced.  Almost 
at  once  the  lever  will  begin  to  rise,  indicating  strong  tonic  contraction. 
The  increase  of  tone  lasts  for  some  time,  but  can  soon  be  removed  on 
washing  the  preparation  with  Ringer.  This  is  most  easily  done,  while  the 
drum  is  stopped,  by  introducing  pipetteful  after  pipetteful  of  Ringer's 
solution  into  the  cylinder  in  the  way  described,  allowing  the  liquid  to 
overflow  into  the  bath.  The  subsequent  addition  of  serum  causes  a 
renewed  increase  of  tone,  and  this  may  be  many  times  repeated. 

Determine  the  greatest  dilution  of  the  serum  which  still  produces  a 
distinct  effect  upon  the  intestinal  segment. 

3.  Action  of  Epinephrin  (Adrenalin)  on  Intestinal  Segments. — Pro- 
ceed as  in  2,  but  use  various  dilutions  of  adrenalin  chloride  instead  of 
serum.  They  must  be  freshly  prepared.  Instead  of  increase  of  tone, 
inhibition  of  the  movements  and  decrease  of  tone  will  be  obtained 
(Fig.  173). 

This  experiment  may  be  performed  at  another  stage  in  the  course 
(P-  693)- 

4.  Quantitative  Estimation  of  Ferment  Action. — For  pepsin  an  easy 
hiethod,  although  not  a  very  accurate  one,  of  estimating  the  rate  at 
which  the  fibrin  disappears  is  to  use  fibrin  stained  with  carmine.  As 
solution  goes  on,  the  dye  colours  the  liquid  more  and  more  deeply,  and 
by  comparing  the  depth  of  colour  at  any  time  with  standard  solutions 
of  carmine,  we  get  the  quantity  of  dye  set  free,  and  therefore  of  fibrin 


448 


DIGESTION  AND  ABSORPTION 


digested.  This  method  cannot  be  used  for  trypsin.  A  much  better 
method  is  that  of  INIett  (p.  336).  Fluid  egg-white  is  sucked  up  into 
fine  glass  tubes  (of  i  to  2  mm.  bore).  The  tubes  are  then  heated  in  a 
bath  at  95°  C.  For  use  short  pieces  (i  or  2  cm.  long)  are  cut  off  and 
placed  in  I  or  2  c.c.  of  the  liquid  to  be  tested,  the  whole  being  kept  at 
38°  to  40°  C. 

For  amylolytic  ferments  where  rapid  work  is  required,  glass  tubes 
filled  with  tinted  starch  paste  may  be  used  in  the  same  way  as  the 
Mett's  tubes.  A  more  accurate  method,  and  yet  a  rapid  and  convenient 
one,  is  based  upon  the  time  which  is  necessary  in  order  that  the  iodine 
reaction  with  starch  may  just  disappear  when  a  standard  starch  solution 

is  digested  with  a  dilution 

of    the    ferment    solution 
at  40°  C. 

5.  Saliva — Collection 
and  Microscopic  Examina- 
tion of  Saliva. — Chew  a 
piece  of  paraffin-wax,  or 
in  hale  ether  or  the  vapour 
of  strong  acetic  acid.  The 
flow  of  saliva  is  increased. 
Collect  it  in  a  porcelain 
capsule.  Examine  a  drop 
under  the  microscope.  It 
Tna.y  contain  a  few  flat 
epithelial  scales  from  the 
mouth  and  a  few  round 
granular  bodies,  the  sali- 
vary corpuscles,  the  gran- 
ules in  which  often  show 
a  lively,  dancing  move- 
ment (Brownian  motion) . 
Filter  the  saliva  to  free  it 
from  air-bubbles,  and  per- 
form the  following  ex- 
periments : 

(a)  Test  the  reaction 
with  litmus  paper.  It  is 
usually  alkaline.  An  acid 
reaction  may  indicate 
that  bacterial  processes 
are  abnormally  active  in 
the  mouth. 
A  precipitate  indicates  the  presence  of 


Fig.  173. — Effect  of  Serum  and  Adrenalin  on  Con- 
tractions of  a  Segment  of  Intestine.  Rabbit's 
intestine  contracting  in  Ringer's  solution.  At 
55  the  Ringer's  solution  was  replaced  by  dog's 
serum,  and  this  at  56  by  adrenalin  (1:5,000,000) 
in  serum.  At  57  this  weak  adrenalin  solution  was 
replaced  by  a  stronger  one  (i;  500,000)  in  serum. 
Time-trace,  half-minutes.     (Reduced  to  half.) 


{b)  Add  dilute  acetic  acid, 
mucin  (p.  338).     Filter. 

(c)  Add  a  drop  or  two  of  silver  nitrate  solution  to  the  filtrate  from 
(b).  A  precipitate  insoluble  in  nitric  acid,  soluble  in  ammonia,  proves 
that  chlorides  are  present. 

{d)  Add  to  another  portion  a  few  drops  of  dilute  ferric  chloride 
slightly  acidulated  with  dilute  hydrochloric  acid,  and  the  same  quantity 
to  as  much  distilled  water  in  a  control  test-tube.  A  reddish  coloration 
is  obtained,  due  to  the  presence  of  sulphocyanic  acid,  which  is  com- 
bined with  potassium  and  other  bases  in  the  saliva.  The  colour  is  dis- 
charged by  mercuric  chloride.  Or,  a  drop  of  saliva  may  be  allowed  to 
fall  from  the  mouth  on  a  test-paper  (prepared  by  soaking  filter-paper 
with  a  dilute  starch  solution,  containing  a  little  iodic  acid,  and  allowing 
it  to  dry  in  the  air).     The  paper  is  coloured  blue  by  the  union  of  the 


PRACTICAL  EXERCISES  449 

starch  with  iodine  set  free  from  the  iodic  acid  by  the  action  of  th«  sulpho- 
cyanic  acid. 

{e)  Take  some  boiled  starch  mucilage,  and  tfst  it  for  reducing  sugar 
by  Trommcr's  test  (p.  10).  If  no  sugar  is  found,  take  three  t<  st- 
tubes,  label  them  A,  B,  C,  and  nearly  half  fill  each  with  the  boiled 
starch.  To  A  add  a  little  saliva,*  to  B  some  saliva  which  has  been 
boiled,  to  C  a  little  saliva  which  has  been  neutralized,  and  as  much 
0-4  per  cent,  hydrochloric  acid  as  has  been  taken  of  the  mucilage,  so  as 
to  make  the  strength  of  the  acid  in  the  mixture  0-2  per  cent.,  a  propor- 
tion well  below  that  of  the  gastric  juice.  Put  the  test-tubes  into  a  water- 
bath  at  40°  C.  In  a  few  minutes  test  the  contents  for  reducing  sugar. 
Abundance  will  be  found  in  A,  none  in  B  or  C.  In  B  the  ferment 
ptyalin  has  been  destroyed  by  boiling;  in  C  its  action  has  been  inhibited 
by  the  acid.  If  the  test-tubes  have  been  left  long  enough  in  the  bath, 
no  blue  colour  will  be  given  by  A  on  the  addition  of  iodine,  but  a  strong 
blue  colour  by  Band  C — i.e.,  the  starch  will  have  completely  disappeared 
from  A. 

(/)  Put  some  starch  in  a  test-tube,  add  a  little  saliva,  and  hold  in  the 
hand  or  place  in  a  bath  at  40°  C.  On  a  porcelain  slab  place  several 
separate  drops  of  dilute  iodine  solution.  With  a  glass  rod  add  a  drop 
of  the  mixture  in  the  test-tube  to  one  of  the  drops  of  iodine  at  intervals 
as  digestion  goes  on.  At  first  only  the  blue  colour  given  by  starch  will 
be  seen;  a  little  later  a  violet  colour,  due  to  the  presence  of  erythro- 
dextrin  in  addition  to  some  unaltered  starch.  A  little  later  the  colour 
will  be  reddish,  the  starch  having  disappeared  and  the  erythrodextrin 
reaction  being  no  longer  obscured.  Later  still  no  colour  reaction  will 
be  obtained,  the  erythrodextrin  having  undergone  further  changes,  and 
only  sugar  (maltose,  isomaltose,  and  perhaps  a  trace  of  dextrose)  and 
achroodextrin — a  kind  of  dextrin  which  gives  no  colour  with  iodine — 
being  present. 

{g)  Put  two  pieces  of  glass  tube  filled  with  tinted  starch  paste  (p.  448) 
into  separate  test-tubes.  Cover  one  with  3  c.c.  and  the  other  with 
6  c.c.  of  saliva.  The  saliva  must  all  be  taken  from  the  same  stock,  and 
must  not  be  collected  separately.  Put  in  a  bath  at  38°  C,  and  when  a 
fair  amount  of  digestion  has  taken  place  in  each,  measure  the  length 
of  the  column  digested,  and  determine  the  relation  between  the  amount 
digested  in  the  two  tubes  (p.  336). 

(/j)  Dilute  2  c.c.  of  saliva  with  distilled  water  up  to  20  c.c,  and  filter. 
Take  six  test-tubes  of  the  same  width,  and  label  them  A,  B,  C,  etc. 
Measure  into  A  3  c.c.  of  the  diluted  saliva,  into  B  2  c.c,  into  C  1-3  c.c, 
into  D  0-9  c.c,  into  E  06  c.c,  and  into  F  0-4  c.c.  Thus  a  series  is  obtained 
in  which  each  tube  contains  (approximately)  two-thirds  as  much  ferment 
as  the  one  it  follows.  Add  distilled  water  to  tubes  B  to  F,  suflicient  to 
make  up  the  volume  in  each  to  3  c.c.  Place  the  tubes  in  a  beaker  of 
iced  water;  add  to  each  10  c.c.  of  a  i  per  cent,  solution  of  boiled  starch 
previously  cooled  in  iced  water,  and  shake  so  as  to  mix  the  contents. 
Each  tube  now  contains  starch  in  uniform  concentration,  and  ferment 
in  varying  concentration.  The  low  temperature  prevents  digestion  till 
all  the  tubes  are  ready.  Now  put  the  tubes  simultaneously  into  a  water- 
bath  at  40°  C.  for  half  an  hour,  and  then  back  again  into  iced  water 
to  prevent  furiner  digestion.  Move  them  about  in  the  iced  water  to 
cool  rapidly.  Fill  up  the  tubes  with  distilled  water  nearly  to  the  top, 
add  a  drop  or  two  of  iodine  solution  to  each,  and  mix  uniformly.  The 
tubes  to  which  the  smallest  amounts  of  saliva  were  added  will  probably 

•  As  it  filters  slowly,  uuiillered  saliva  may  be  used  for  Experiments  {e), 
(/),and(i). 

29 


450  DIGESTION  AND  ABSORPTION 

still  show  a  distinct  blue  colour,  while  those  at  the  other  end  of  the 
series  will  be  brown  or  yellow,  and  the  intermediate  tubes  bluish-violet. 
Suppose  D  is  the  last  tube  still  showing  a  bluish  tint,  then  in  the  next 
higher  tube,  C,  all  the  starch  has  been  hydrolysed  at  least  to  dextrin — 
that  is,  1*3  c.c.  of  the  ten-times  diluted  saliva,  or  0'i3  of  the  original 
saliva,  has  been  sufficient  to  change  all  the  starch  in  lo  c.c.  of  the  i  per 
cent,  solution.  With  another  specimen  of  saliva  the  same  result  might 
be  reached  in  tube  E,  containing  an  amount  of  ferment  equal  to  that 
in  0'o6  c.c.  of  the  original  saliva.  We  could  then  conclude  that  the 
diastatic  power  of  the  second  saliva  was  about  twice  as  great  as  that 
of  the  first.  A  closer  approximation  can  now  be  made  by  setting  up 
two  fresh  tubes  (C  and  E  respectively  for  the  two  salivas)  and  deter- 
mining the  time  required  for  the  blue  reaction  with  iodine  to  disappear, 
taking  out  a  drop  from  time  to  time  and  testing  on  a  porcelain  slab. 

(^)  Put  a  little  distilled  water  into  a  porcelain  capsule,  and  bring  the 
water  to  the  boil.  Now  put  into  the  mouth  some  boiled  starch  paste, 
and  move  it  about  as  in  mastication.  After  half  a  minute  spit  the 
starch  out  into  the  boiling  water.  Divide  the  water  into  two  portions. 
Test  one  for  sugar,  and  the  other  for  starch.  Repeat  the  experiment, 
but  keep  the  starch  two  minutes  in  the  mouth.     Report  the  result. 

(;')  Starch  solution  to  which  saliva  has  been  added  is  placed  in  a 
dialyser  tube  of  parchment-paper  for  twenty-four  hours.  At  the  end 
of  that  time  the  dialysate  (the  surrounding  water)  should  be  tested  for 
sugar  and  for  starch.  Sugar  will  probably  be  found,  but  no  starch. 
If  no  reaction  for  sugar  is  obtained,  the  dialysate  should  be  concen- 
trated on  the  water-bath,  and  again  tested. 

6.  Stimulation  of  the  Chorda  Tympani. — (i)  Having  previously 
studied  the  anatomy  of  the  mouth  and  submaxillary  region  in  the  dog 
by  dissecting  a  dead  animal  (Fig.  174),  put  a  good-sized  dog  under 
morphine.  Set  up  an  induction-machint  for  a  tetanizing  current 
(p.  198),  and  connect  it  with  fine  electrodes.  Fasten  the  dog  on  the 
holder,  give  ether  if  necessary,  and  insert  a  cannula  in  the  trachea 
(p.  199).  Then  make  an  incision  3  or  4  inches  long  through  skin  and 
platysma  muscle,  along  the  inner  border  of  the  lower  jaw,  beginning 
about  the  angle  of  the  mouth,  and  continuing  backwards  towards  the 
angle  of  the  jaw.  Such  branches  of  the  jugular  vein  as  come  in  the  way 
may  be  generally  pushed  aside,  but  if  necessary  they  may  be  doubly 
ligated  and  divided.  Feel  for  the  facial  artery,  so  as  to  be  able  to 
avoid  it.  Divide  the  digastric  muscle  about  its  anterior  third,  and 
clear  it  carefully  from  its  attachments;  or,  without  dividing  it,  pull  it 
outwards  with  a  hook.  The  broad,  thin  mylo-hyoid  muscle  will  now 
be  seen  with  its  motor  nerve  lying  on  it.  Divide  the  muscle  about  its 
middle  at  right  angles  to  its  fibres,  and  raise  it  carefully.  The  lingual 
nerve  will  be  seen  emerging  from  under  the  ramus  of  the  jaw.  It  runs 
transversely  towards  the  middle  line,  and  then,  bending  on  itself,  passes 
forwards  parallel  to  the  larger  hypoglossal  nerve.  In  its  transverse 
course  the  lingual  will  be  seen  to  cross  the  ducts  of  the  submaxillary 
and  sublingual  glands.  These  structures  having  been  identified,  the 
lingual  nerve  is  to  be  ligatured  before  it  enters  the  tongue  and  cut 
peripherally  to  the  ligature.  Then  a  glass  cannula  of  suitable  size  is  to 
be  inserted  into  the  submaxillary  duct  (the  larger  of  the  two),  just  as  if 
it  were  a  bloodvessel  (p.  63).  A  short  piece  of  narrow  rubber  tubing 
is  carefully  slipped  on  the  end  of  the  cannula.  The  lingual  is  now  to  be 
lifted  by  means  of  the  ligature,  and  traced  back  tov/ards  the  jaw  till  its 
chorda  tympani  branch  is  seen  coming  off  and  nmning  backwards  along 
the  duct.  The  chordo-lingual  nerve  (Fig.  160,  p.  386)  is  then  to  be 
cut  centrally  to  the  origin  of  the  chorda  tympani,  which  can  now  be 


PRACTICAL  EXERCISES 


451 


easily  laid  on  electrodes  by  means  of  the  ligature  on  the  lingual.  On 
stimulating  the  chorda,  the  flow  of  saliva  through  the  cannula  will  be 
increased.  The  current  need  not  be  very  strong.  If  the  flow  stops 
after  a  short  time,  it  can  be  again  caused  by  renewed  stimulation  after 
a  brief  rest.  A  quantity  of  saliva  may  thus  be  collected,  and  the  experi- 
ments already  made  with  liuman  saliva  repeated. 

{2)  Expose  the  vago-sympathetio  nerve  in  the  neck  on  the  same 
side;  ligature  it;  divide  below  the  ligature;  and  note  the  effect  pro- 
duced by  stimulation  of  the  upper  end  on  the  flow  of  saliva. 

(3)  Set  up  another  induction-machine,  and  connect  it  with  electrodes. 
Stimulate  the  chorda,  and  note  the  rate  of  flow  of  the  saliva.  Then, 
while  the  chorda  is  still  being  excited,  stimuLite  the  vago-sympathetic, 
and  observe  the  effect.  If  the  experiment  is  successful,  finish  by 
stimulating  the    chorda   for   a   long  time.      Then    harden    both    sub- 


Digastric 

Muscle  (cut). 


Mylo-hyoid         Ungiia 
Muscle  (cut).        Nerve. 


Wharton's 
Duct. 


Fig.  174. — Dissection  for  Stimulation  of  Chorda  Tyrnpani  (after  Bernard). 


maxillary  glands  in  absolute  alcohol,  make  sections,  stain  with  carmine, 
and  compare  them. 

7.  Effect  of  Drugs  on  the  Secretion  of  Saliva. — (i)  Proceed  as  in 
6  (i),  but,  in  addition,  insert  a  cannula  into  the  femoral  vein  (p.  217). 
On  the  cannula  put  a  short  piece  of  rubber  tubing,  filled  with  o-g  per 
cent,  salt  solution  and  closed  by  a  small  clamp,  or  a  small  piece  of 
glass  rod,  or  a  pair  of  bulldog  forceps.  While  the  chorda  is  being 
stimulated  inject  into  the  vein  10  to  15  milligrammes  of  sulphate  of 
atropine  by  pushing  the  needle  of  a  hypodermic  syringe  through  the 
rubber  tube.  This  will  stop  the  flow  of  saliva,  and  abolish  the  effect 
of  stimulation  of  the  chorda.  See  whether  the  sympathetic  is  also 
inactive,  and  report  the  result. 

(2)  Now  empty  the  cannula  in  the  submaxillary  duct  by  means  of  a 
feather,  and  fill  it  with  a  2  per  cent,  solution  of  pilocarpine  nitrate  by 
means  of  a  fine  pipette.  Fill  also  the  short  rubber  tube  attaclied  to 
the  cannula,  and  close  it  again.     Compress  the  tube,  and  so  force  into 


452  DfGESTION   AND  ABSORPTION 

the  duct  a  small  quantity  of  the  solution.  Open  the  tube.  Secretion 
of  saliva  will  again  begin,  and  stimulation  of  the  chorda  will  again  cause 
an  increase  in  the  flow.  But  after  a  few  minutes  tlie  action  of  the 
atropine  will  reassert  itself,  and  the  flow  will  stop.  Renewed'  secretion 
may  be  caused  by  a  fresh  injection  of  pilocarpine. 

8.  Gastric  Juice — [a)  Preparation  of  Artificial  Gastric  Juice. — ^Take 
a  portion  of  the  pig's  stomach  provided,  strip  off  the  mucous  membrane 
(except  that  of  the  pyloric  end,  which  is  relatively  poor  in  pepsin),  cut 
it  into  small  pieces  with  scissors,  and  put  it  in  a  bottle  with  loo  times 
its  weight  of  0-4  per  cent,  hydrochloric  acid.  Label  and  put  in  a  bath 
at  40°  C.  for  three  hours,  and  then  in  the  cold  for  twelve  hours.  Then 
filter. 

{b)  Take  another  portion  of  the  mucous  membrane,  cut  it  into  pieces, 
and  rub  up  with  clean  sand  in  a  mortar.  Then  put  it  in  a  small  bottle, 
cover  it  with  glycerin,  label,  and  set  aside  for  two  or  three  days.  The 
glycerin  extracts  the  pepsin. 

(c)  Take  five  test-tubes,  A,  B,  C,  D,  E,  and  in  each  put  a  little  washed 
and  boiled  fibrin  or  a  small  cube  of  coagulated  egg-white.  To  A  add  a 
few  drops  of  glycerin  extract  of  pig's  stomacji,  and  fill  up  the  test-tube 
with  0'4  per  cent,  hydrochloric  acid.  To  B  add  glycerin  extract  and 
distilled  water;  to  C  glycerin  extract  and  i  per  cent,  sodium  carbonate; 
to  D  o*4  per  cent,  hydrochloric  acid  alone ;  to  E  glycerin  extract  which 
has  been  boiled,  and  0-4  per  cent,  hydrochloric  acid. 

Put  up  another  set  of  five  test-tubes  in  the  same  way,  except  that  a 
few  drops  of  a  watery  solution  of  a  commercial  pepsin  are  substituted 
for  the  glycerin  extract.     Label  the  test-tubes  A',  B',  C,  D',  E'. 

Into  another  test-tube  put  a  little  fibrin  (or  an  egg-white  cube),  and 
fill  up  with  the  filtered  acid  extract  from  («).  Label  it  F.  Place  all 
the  test-tubes  in  a  tumbler,  and  set  them  in  a  water-bath  at  40°  C. 
Put  a  piece  of  a  Mett's  tube  (p.  336)  into  each  of  two  test-tubes,  and 
add  15  c.c.  of  0'4  per  cent,  hydrochloric  acid.  To  one  tube  add  5  drops 
and  to  the  other  10  drops  of  the  same  filtered  glycerin  extract  of  gastric 
mucous  membrane.  Put  the  tubes  in  the  bath,  and  when  digestion  is 
distinct  at  the  ends  of  both  tubes  measure  the  length  of  the  column 
digested  in  each.  What  is  the  relation  between  the  two  (p.  336)  ? 
The  experiment  can  be  repeated  with  the  hydrochloric  acid  extract  of 
the  mucous  membrane. 

After  a  time  the  fibrin  (or  egg-white)  will  have  almost  completely  dis- 
appeared in  A,  A',  and  F,  but  not  in  the  other  test-tubes.  Filter  the 
contents  of  A,  A  ,  and  F  into  one  dish. 

{d)  Test  the  filtrate  for  the  products  of  gastric  digestion : 

(a)  Neutralize  a  portion  carefully  with  dilute  sodium  hydrox- 
ide. A  precipitate  of  acid-albumin  may  be  thrown 
down.  Filter. 
0)  To  a  portion  of  the  filtrate  from  (a)  add  excess  of  sodium 
hydroxide  and  a  drop  or  two  of  very  dilute  copper 
sulphate.  A  rose  colour  indicates  the  presence  of 
proteoses  or  peptones.  The  cupric  sulphate  must  be 
very  cautiously  added,  because  an  excess  gives  a  violet 
colour,  and  thus  obscures  the  rose  reaction.  If  still 
mere  cupric  sulphate  be  added,  blue  cupric  hydroxide 
is  thrown  down,  and  nothing  can  be  inferred  as  to  the 
presence  or  the  nature  of  proteins  in  the  liquid, 
(y)  Heat  another  portion  of  the  filtrate  from  («)  to  30°  C, 
and  add  crystals  of  ammonium  sulphate  to  saturation. 
A  precipitate  of  proteoses  (albumoses)  may  be  ob- 
tained.    Filter  off. 


PRACTICAL  EXERCISES  453 

(8)  Add  to  the  filtrate  from  (y)  a  trace  of  cupric  sulphate  and 
excess  of  sodium  hydroxide.  A  rose  colour  indicates 
that  peptones  are  })rescnt.  More  sodium  hydroxide 
must  be  added  than  is  sufficient  to  break  up  all  the 
ammonium  sulphate,  for  the  biuret  reaction  requires 
the  presence  of  free  fixed  alkali.  A  strong  solution  of 
the  sodium  hydroxide  should  therefore  be  used,  or  the 
stick  caustic  soda.  The  addition  of  ammonium  sul- 
phate will  cause  the  red  colour  to  disappear;  so  will  the 
addition  of  an  acid.  Sodium  hydroxide  will  bring  it 
back.  Ammonia  does  not  affect  the  colour. 
{e)  To  some  milk  in  a  test-tube  add  a  drop  or  two  of  rennet  extract, 

and  place  in  a  bath  at  40°  C.     In  a  short  time  the  milk  is  curdled  by 

the  Rnnin.      (Sec  p.  347.) 

9.   (i)  To  obtain  Normal  Chyme. — Inject  subcutaneously  into  a  dog, 

one  and  a  half  hours  after  a  meal  of  minced  meat  and  water,  2  mg.  of 

apomorphine.     Half  of  one  of  the  ordinary  tabloids  is  enough.     Collect 

the  \omit. 

(2)  To  obtain  Pure  Gastric  Juice. — If  the  laboratory  possesses  a  dog 
with  Pawlow's  double  ocsojjhagcal  and  gastric  fistula,  the  juice  may 
be  obtained  in  large  amount  by  sham  feeding  with  meat  (p.  395)-  ^^ 
not,  proceed  as  follows:  Put  a  fasting  dog  under  ether,  and  fasten  on 
the  holder.  Clip  the  hair  and  shave  the  skin  in  the  middle  line  below 
the  sternum.  Make  a  longitudinal  incision 
through  the  skin  and  subcutaneous  tissue 
from  the  xiphoid  cartilage  downwards  for 
3  or  4  inches.  The  linea  alba  will  now  be  seen 
as  a  white  mesial  streak.  Open  the  abdomen 
by  an  incision  through  it.  Pull  over  the 
stomach  towards  the  right,  and  stitch  it  to 
the  abdominal  wall,  open  it,  and  insert  a 
stomach  cannula  (Fig.  175).  Make  an  incision  Fig.  175.— Stomach 
through  the  serosa  and  muscularis.     Doubly  Cannula. 

ligate  and  divide  any  vessels  exposed  in  the 

submucosa.  Then  make  an  opening  in  the  mucosa  of  sufficient  size  to 
just  admit  the  gastric  cannula.  This  will  go  into  a  smaller  opening  if  it 
is  provided  with  a  nick  in  the  flange  which  enters  the  stomach.  Be 
careful  to  prevent  blood  from  getting  into  the  stomach.  Immediately 
stitch  the  wound  in  the  stomach  over  the  flange  of  the  cannula,  but 
do  not  pass  the  stitches  through  to  the  internal  surface  of  the  mucosa. 
Suture  the  muscles  and  skin  separately.  Then  stitch  up  the  wound  in 
tlic  abdomen.  Wash  out  any  stomach  contents  with  warm  water.  Put 
a  cork  in  the  cannula,  and  cover  the  animal  with  a  cloth.  The  follow- 
ing experiments  may  now  be  performed:  Expose  both  vagi  in  the  neck. 
Connect  two  pairs  of  electrodes  with  the  secondary  coil  of  an  induc- 
torium  arranged  for  single  shocks.  By  means  of  a  key  in  the  primary 
stimulate  the  nerves  with  slow  rhythmical  induction  shocks  at  the  rate 
of  about  one  a  second.  Continue  the  stimulation  for  fifteen  minutes, 
collect  any  juice  that  may  have  been  secreted,  and  apply  the  tests  in  (3). 
If  secretion  is  slow,  a  little  distilled  water  may  be  put  into  the  stomach, 
and  the  vagus  stimulation  repeated.  Mechanical  stimulation  of  the 
mucous  membrane  with  a  feather  caus-es  no  secretion  of  acid  gastric 
juice,  but  may  cause  a  secretion  of  alkaline  mucus. 

(3)  (a)  Test  the  reaction  to  litmus  of  the  chyme  obtained  in  (i),  and 
of  the  pure  juice  obtained  in  (2). 

(b)  Test  their  proteolytic  powers  by  putting  in  a  bath  at  40^  C.  for 
two  hours  two  test-tubes  containing  respectively  filtered  chyme  and 


454  DIGESTION  AND  ABSORPTION 

fibrin,  and  gastric  juice  and  fibrin.     The  fibrin  will  be  digested  in  both. 
Estimate  the  proteolytic  power  quantitatively  by  Mett's  tubss  (p.  448). 

(c)  Add  a  few  drops  of  the  chyme  and  gastric  juice  to  milk  in  two 
test-tubes,  and  place  them  in  a  bath  at  40°  C.  Repeat  (c)  afterneulral- 
izing  the  liquids. 

{d)  Examine  a  drop  of  the  unfiltered  chyme  under  the  microscope. 
Partially  digested  fragments  of  the  food  will  be  seen — muscular  fibres 
or  fat  cells.     Filter,  and  proceed  as  in  8  {d)  (p.  453). 

(4)  Test  the  filtrate  from  the  chyme  and  the  gastric  juice  for  lactic 
acid  by  Uffelmann's  test  or  Hopkins's  test  (p.  794),  and  for  hydrochloric 
acid  by  Gunzburg's  reagent. 

Uffelmann's  Test  for  Lactic  Acid. — The  reagent  is  a  dilute  solution 
of  carbolic  acid  to  which  dilute  ferric  chloride  has  been  added  till  the 
colour  is  bluish  (say  a  drop  of  a  i  per  cent,  ferric  chloride  solution  to 
5  c.c.  of  a  I  per  cent,  carbolic  acid  solution).  The  blue  colour  of  the 
mixture  is  turned  yellow  by  lactic  acid,  but  not  by  dilute  hydrochloric 
acid.  Since  Uffelmann's  test  is  given  also  by  phosphates,  alcohol,  and 
sugar,  which  may  sometimes  be  present  in  the  stomach  contents,  it  is 
best  to  shake  the  gastric  contents  with  ether,  dissolve  the  ethereal 
extract  in  water,  and  then  make  the  test  on  the  watery  solution. 

Giinzburg's  Reagent  for  Free  Hydrochloric  Acid  in  Gastric  Juice  is 
made  by  dissolving  2  parts  of  phloroglucinol  and  i  part  of  vanillin  in 
30  parts  by  weight  of  absolute  alcohol.  A  few  drops  of  the  reagent 
are  added  to  a  few  drops  of  the  filtered  gastric  juice  in  a  small  porcelain 
capsule,  and  the  whole  evaporated  to  dryness  over  a  small  bunsen 
flame.  If  free  hydrochloric  acid  is  present,  a  carmine-red  residue  is 
left.  If  all  the  hydrochloric  acid  is  united  to  proteins  in  the  stomach 
contents,  the  reaction  does  not  succeed.  It  is  also  hindered  by  the 
presence  of  leucin. 

10.  Pancreatic  Juice. — (a)  Take  a  piece  of  the  pancreas  of  an  ox  or 
dog  which  has  been  kept  twenty-four  hours  at  the  tempsrature  of  the 
laboratory,  and  make  a  glycerin  extract  in  the  same  way  as  in  the 
case  of  the  pig's  stomach  in  8  {b).  Put  in  a  small  bottle,  and  set  aside 
for  a  day  or  two. 

(6)  Put  a  little  boiled  fibrin  into  each  of  six  test-tubes.  A,  B,  C,  D,  E, 
F.  To  A  add  a  few  drops  of  glycerin  extract  of  pancreas,  and  fill  up 
with  a  I  per  cent,  sodium  carbonate  solution ;  to  B  add  glycerin  extract 
and  distilled  water;  to  C  glycerin  extract  and  excess  of  005  per  cent, 
hydrochloric  acid ;  to  D  i  per  cent,  sodium  carbonate  alone;  to  E  i  per 
cent,  sodium  carbonate  in  which  a  few  drops  of  glycerin  extract  of 
pancreas  have  been  previously  boiled ;  to  F  glycerin  extract  and  excess 
of  0'2  per  cent,  hydrochloric  acid.* 

Set  up  six  test-tubes,  A',  B',  C,  D',  E',  F',  in  the  same  way,  but 
substitute  a  few  drops  of  a  solution  of  commercial  pancrcatin  for  the 
glycerin  extract.  Set  up  two  test-tubes  as  in  experiment  8  (p.  452) 
with  Mett's  tubes.  Put  all  the  test-tubes  in  a  tumbler,  and  place  in  a 
bath  at  40°  C.  The  fibrin  will  be  gradually  eaten  away  in  A  and  A^ 
by  the  action  of  the  trypsin,  but  will  not  swell  up  or  become  clear 
before  disappearing,  as  it  does  in  dilute  hydrochloric  acid  with  glycerin 

*  With  hydrochloric  acid  of  different  strengths  the  rapidity  of  digestion 
of  boiled  fibrin  by  glycerin  extract  of  dog's  pancreas  (i  volume  of  extract 
to  25  of  acid)  was  found  about  the  same  for  0*3  and  o'ly  per  cent,  acid;  much 
less  for  o'o8  per  cent.,  while  in  0*04  per  cent,  acid  there  was  practically  no 
digestion  at  all.  In  0-4  per  cent,  acid  digestion  took  place  more  rapidly  than 
in  o'o8  per  cent.,  but  much  less  rapidly  than  in  0-17  per  cent.  In  acid  of  all 
strengths  digestion  was  markedly  slower  than  in  i  per  cent,  sodium  car- 
bonate. 


PRACTICAL  EXERCISES  455 

extract  of  stomach.  Filter  the  contents  of  these  test  tubes.  Neutralize 
the  filtrate  with  dilute  acid;  a  precipitate  will  consist  of  alkali-albumin. 
If  such  a  precipitate  is  obtained,  filter  it  oft  and  test  the  filtrate  for 
proteoses  and  peptones  as  in  8  {d)  (p.  452).  Some  digestion,  and  perhaps 
a  considerable  amount,  may  also  have  taken  place  in  F  and  F';  less 
or  none  at  all  in  C  and  C;  and  none  in  the  other  ^cst-tubes  (pp.  353,  415). 

(c)  Add  a  few  drops  of  the  glycerin  extract  to  a  test-tube  containing 
starch  mucilage,  which  has  been  previously  found  free  from  reducing 
sugar.  Put  in  a  bath  at  40°  C.  After  a  short  time  abundance  of 
reducing  sugar  will  be  found,  owing  to  the  action  of  the  ferment, 
amylopsin,  or  pancreatic  amylase. 

(d)  Mince  thoroughly  a  good-sized  piece  of  fresh  pancreas,  and  shako 
up  well  with  three  or  four  times  its  bulk  of  water.  Put  5  c.c.  of  fresh 
cream  into  a  test-tube,  then  10  c.c.  of  the  extract,  a  few  drops  of  chloro- 
form to  prevent  the  growth  of  bacteria,  a  few  drops  of  litmus  solution, 
and  if  necessary  enough  of  vcr>'  dilute  sodium  hydroxide  to  just  render 
the  colour  distinctly  blue.  Shake  up,  and  divide  the  mixture  into  two 
portions,  A  and  B.  Boil  one  portion  (B),  and  place  the  test-tubes  at 
40°  C.  Examine  from  time  to  time.  The  blue  colour  will  disappear  in 
A,  owing  to  the  formation  of  fatty  acids  from  the  neutral  fats,  and 
sodium  hydroxide  must  be  added  to  it  to  restore  the  colour.  In  B  the 
fat-splitting  ferment  has  b:?cn  destroyed  by  boiling,  and  fat-splitting 
will  not  occur.  Probably  a  distinct  result  will  not  be  obtained  for 
several  hours,  and  it  will  be  best  to  leave  the  tubes  in  the  incubator 
overnight. 

{e)  If  the  laboratory  possesses  an  animal  with  a  pancreatic  fistula, 
the  following  experiment  may  be  done  by  a  limited  number  of  students 
with  fresh  pancreatic  juice*  collected  from  the  fistula.  Take  five  test- 
tubes,  A,  B,  C,  D,  E.  Add  5  c.c.  of  pancreatic  juice  to  each  tube.  Boil 
E,  and  then  cool  it.  Put  into  A  and  B  small  pieces  of  heat-coagulated 
egg-white,  into  C  a  little  starch  mucilage,  and  into  D  and  E  5  c.c.  of 
fresh  cream.  Add  further  to  B  a  scraping  of  the  mucous  membrane  of 
the  upper  part  of  the  small  intestine  which  has  first  been  washed  free  of 
contents.  To  D  and  E  add  a  drop  or  two  of  litmus  solution,  and,  if 
necessary,  enough  of  dilute  sodium  hydroxide  to  just  establish  a  blue 
colour.  Then  put  the  test-tubss  at  40°  C,  and  examine  after  a  time. 
No  digestion  will  have  taken  place  in  A,  because  the  pancreatic  juice,  as 
secreted,  does  not  contain  active  trypsin.  In  B  digestion  may  take 
place,  because  the  entero kinase  in  the  intestinal  mucous  membrane 
will  activate  the  trypsinogen  to  trypsin.  In  C  and  D  there  will  be 
evidence  of  the  production  of  reducing  sugar  and  fatty  acids  respec- 
tively, since  the  pancreatic  juice,  as  secreted,  contains  active  amylase 
and  steapsin.     E  will  be  unchanged  unless  by  bacterial  action. 

(/)  Leucin  and  2'yrosin. — As  examples  of  amino-acids  formed  when 
pancreatic  digestion  of  proteins  (fibrin  or  casein,  e.g.)  is  allowed  to  go 
on  for  .some  days, f  leucin  and  tryosin  maybe  isolated.  Add  bromine- 
water  by  drops  to  5  c.c.  of  the  digest;  a  pink  colour  indicates  tn,'pto- 
phane.  If  the  '  digest  '  be  neutralized,  then  filtered,  and  the  filtrate 
concentrated  and  allowed  to  stand,  a  crop  of  tyrosin  crystals  will 
separate  out,  since  tyrosin  is  only  slightly  soluble  in  watery'  solutions 
of  neutral  salts.  These  crystals  having  been  filtered  off,  the  proteoses 
(albumoses)  and  peptones  can  be  precipitated  together  by  alcohol,  and 

*  A  considerable  flow  of  pancreatic  juice  can  be  obtained  from  a  dog  with 
a  pancreatic  fistula  by  injecting  intravenously  an  extract  of  intestinal  mucous 
membrane  containing  secretin  (p.  401). 

•f  A  little  chloroform  is  added  to  prevent  bacterial  growth. 


456  DIGESTION  AND  ABSORPTION 

afterwards  separated,  if  that  is  desired,  by  redissolving  the  precipitate 
in  water  and  throwing  down  the  proteoses  by  saturation  with  am- 
monium sulphate.  The  alcohohc  filtrate  will  contain  any  leucin  that 
may  be  present,  since  that  body  is  moderately  soluble  in  alcohol,  as 
well  as  traces  of  tyrosin,  which,  however,  is  much  less  soluble  in  this 
medium.  On  concentration,  crystals  of  both  substances  will  be  ob- 
lained.  Tyrosin  crystallizes  characteristically  from  animal  liquids  in 
beautiful  silky  needles  united  into  sheaves,  leucin  in  the  form  of  in- 
distinct fatty-looking  balls,  often  marked  with  radial  striae  and  coloured 
with  pigment  (Figs.  i86  and  187,  p.  483). 

Tests  for  Tyrosin  by  Morner's  Test. — Put  a  small  quantity  of  tyrosin 
into  a  test-tube.  Add  about  3  c.c.  of  the  reagent,*  and  heat  gradually 
and  gently  to  the  boiling-point.     A  green  colour  is  obtained. 

II.  Bile. — (fl)  Test  the  reaction  of  ox  bile.     It  is  alkaline  to  litmus. 

(b)  Add  dilute  acetic  acid.  A  precipitate  of  bile-mucin  (really 
nucleo-albumin)  falls  down.  Some  of  the  bile-pigment  is  also  pre- 
cipitated. Filter.  (Pig's  bile  contains  more  of  the  ^ucin-like  sub- 
stance than  ox  bile.) 

(c)  Put  a  little  of  the  filtrate  from  (6)  or  of  the  original  bile  into  a 
porcelain  capsule,  add  a  drop  or  two  of  a  dilute  solution  of  cane-sugar, 
and  mix  with  the  bile.  Then  add  a  few  drops  of  strong  sulphuric  acid, 
and  stir;  then  a  few  drops  more  of  the  sulphuric  acid,  stirring  all  the 
time.  A  purple  colour  appearing  at  once,  or  after  gentle  heating, 
shows  the  presence  of  bile-acids  (Pettenkofer's  reaction).  The  bile 
may  be  diluted  before  the  addition  of  the  sulphuric  acid.  In  this  case 
a  greater  amount  of  the  acid  must  be  added.  Examine  the  purple 
liquid  in  a  test-tube  with  a  spectroscope  (p.  74).  Dilute  the  liquid  with 
water,  adding  some  sulphuric  acid  to  partially  clear  up  the  precipitate 
caused  by  the  water.  Two  absorption  bands  are  seen,  one  to  the  red 
side  of  D,  and  the  other,  a  stronger  and  broader  band,  over  and  to  the 
right  of  E.  When  only  a  very  small  amount  of  bile-salts  is  present, 
the  reaction  is  made  more  sensitive  if  a  solution  of  furfuraldehyde  (i  to 
1,000)  is  used  instead  of  cane-sugar. 

{d)  Hay's  Sulphur  Test. — Sprinkle  a  little  sulphur  (in  the  form  of 
the  fine  powder  known  as  flowers  of  sulphur)  on  the  surface  of  some 
bile  in  a  small  beaker  or  deep  watch-glass.  The  sulphur  will  soon  sink 
to  the  bottom.  Repeat  with  water;  the  sulphur  will  float.  The 
reaction  is  due  to  the  diminution  of  the  surface  tension  produced  by 
the  bile-acids,  and  succeeds  also  in  a  solution  of  bile-salts.  The  test 
is  very  sensitive.  But  in  stomach  contents,  vomit,  or  stools,  it  rarely 
gives  good  results,  since  alcohol  or  acetic  acid  is  often  present  in  the 
gastric  liquid,  and  phenol  and  i':s  derivatives  in  intestinal  contents, 
and  all  of  these  cause  such  an  alteration  in  the  surface  tension  that  the 
sulphur  sinks.  Ether,  chloroform,  turpentine,  benzine  and  its  deriva- 
tives, anilin  and  soaps,  also  vitiate  the  test  in  the  same  way. 

{e)  Add  yellow  nitric  acid  (containing  nitrous  acid)  to  a  little  bile  on 
a  white  porcelain  slab.  A  play  of  colours,  beginning  with  green  and 
running  through  blue  to  yellow  and  yellowish-brown,  indicates  the 
presence  of  bile-pigment  (Gmelin's  reaction).  The  reaction  may  also 
be  obtained  by  putting  some  yellow  nitric  acid  into  a  test-tube,  and 
then  running  a  little  bile  from  a  pipette  on  to  the  surface  of  the  acid. 
The  play  of  colours  is  seen  at  the  surface  of  contact.  Where  the  bile- 
pigment  is  present  only  in  traces,  some  of  the  liquid  may  be  filtered 

*  The  reagent  for  this  test  is  p  epired  by  mixi  ig  thoroughly  i  volume  of 
fo  malin,  45  volumes  of  distilled  water,  and  55  volumes  of  concentrated 
su'i>huric  acid. 


PRACTICAL  EXERCISES  457 

through  white  filter-pap3r,  and  the  test  applied  by  putting  a  drop  of 
the  nitric  acid  on  the  paper. 

[f)  Cholesterin  or  Cholesterol  (Fig.  176) — Pre  pa/a' ion. — Extract  a 
powdered  gall-stone  (preferably  a  white  one)  with  hot  alcohol  and  ether 
in  a  test-tube.  Heat  the  test-tube  in  warm  water,  not  in  the  free  flame. 
Put  a  drop  of  the  extract  on  a  slide.  Flat  crystals  of  cholesterin,  often 
chipped  at  the  comers,  separate  out.  (a)  Carefully  allow  a  drop  of 
strong  sulphuric  acid  and  a  drop  of  dilute  iodine  to  run  under  the  cover- 
glass.     A  play  of  colours — violet,  blue,  green,  red — is  seen. 

(3)  Evaporate  a  drop  of  the  solution  of  cholesterin  in  a  small  porce- 
lain capsule,  add  a  drop  of  strong  nitric  acid,  and  heat  gently  over  a 
flame.  A  yellow  stain  is  left,  which  becomes  red  when  a  drop  of  am- 
monia is  poured  on  it  while  it  is  still  warm. 

(7)  Dissolve  a  little  cholesterin  in  chloroform.  Add  an  equal  bulk 
of  strong  sulphuric  acid,  and  shake  gently-  The  solution  turns  red 
and  the  subjacent  acid  shows  a  green  fluorescence. 

(^)  Put  a  drop  or  two  of  water  in  a  watch-glass,  and  add  a  drop  of  an 
ethereal  solution  of  cholesterin.  The  cholesterin  is  precipitated,  and 
will  not  dissolve  in  the  water  even  on  heating.  Repeat  tlie  observation 
with  bile  instead  of  water.     The  cholesterin  dissolves  in  the  bile. 

(g)  To  a  little  of  the  filtrate  from  a 
p3ptic  digest  {e.g.,  fibrin  which  has  been 
digested  for  twenty-four  hours  with 
p;psin  and  hydrochloric  acid)  add  some 
bile.  A  precipitate  is  thrown  down, 
which  is  redissolved  in  excess  of  the 
bile  (p.  364). 

[h)  Shake  up  a  little  bile  with  some 
rancid  olive-oil  in  a  test-tube .  An  emul- 
sion is  formed.  Repeat  the  experiment 
with  the  same  quantities  of  bile  and  oil, 
but  use  perfectly  fresh  oil.  Compare  the 
stability  of  the  two  emulsions,  allowing 
the  tubes  to  stand  together  for  a  while.      Fig.  176.— Crystals  of  Cholesterin 

(i)  To  some  starch  mucilage,  shown  (Frey). 

to  be  free  from  sugar,  add  a  little  bile, 

and  place  in  a  bath  at  40°  C.     After  a  time  test  for  reducing  sugar. 
Report  the  result.     Bile  often  has  a  slight  diastatic  power. 

(/)  To  demonstrate  the  Presence  of  Iron  in  the  Liver  Cells. — Steep  sec- 
tions of  liver  in  a  solution  of  potassium  ferrocyanide,  and  then  in  dilute 
hydrochloric  acid.  Or  a  i  -5  per  cent,  solution  of  potassium  ferrocyanide 
in  0-5  per  cent,  hydrochloric  acid  may  be  used.  (The  iron  may  pre- 
viously be  fixed  in  the  tissue  by  hardening  it  in  a  mixture  of  alcohol 
and  ammonium  sulpliide.)  The  sections  become  bluish  from  the 
formation  of  Prussian  blue.  A  fine-pointed  glass  rod  or  a  platinum 
lifter  should  be  used  in  manipulating  them.  A  steel  needle  cannot  be 
employed.  Mount  in  glycerin^ or  Farrant's  solution,  or  (after  dehy- 
drating with  alcohol  and  clearing  in  xylol)  in  xylol-balsam.  Blue 
granules  may  be  seen  under  tho  microscope  in  some  of  the  hepatic  cells. 
Sections  of  spleen  may  also  be  examined  for  this  reaction. 

12.  Microscopical  Examination  of  Faeces. — Examine  luid^r  the  micro- 
scope the  slides  provided.  Draw,  and  as  far  as  possible  determine  the 
nature  of.  the  objct is  seen  (p.  418). 

13.  Absorption  of  Fat. — {a)  Feed  a  rat  or  frog  with  fatty  food;  kill 
the  rat  in  thr^e  or  four  hours,  the  frog  in  two  or  throe  days.  Imme- 
diately after  killing  the  rat  open  the  abdomen,  carefully  draw  out  a 
loDp  of  intestine,  and  look  through  the  thin   mesentery.     The  white 


458  DIGESTION  AND  ABSORPTION 

lacteals  will  probably  be  seen  ramifying  in  the  mesentery.  They 
appear  white  on  account  of  the  presence  of  globules  of  fat  in  the  chyle 
with  which  they  are  filled.  Strip  off  tiny  pieces  of  the  mucous  mem- 
brane of  the  small  intestine,  and  steep  them  in  J  per  cent,  solution  of 
osmic  acid  for  forty-eight  hours.  Then  tease  fragments  of  the  mucous 
membrane  in  glycerin  and  examine  under  the  microscope.  To  preserve 
the  specimens  take  off  the  glycerin  with  blotting-paper  and  mount  in 
Farrant's  medium,  which  is  a  preservative  glycerin  mixture.  Other 
portions  of  the  mucous  membrane  may  be  hardened  for  a  fortnight  in 
a  mixture  of  2  parts  of  Miiller's  fluid  and  i  part  of  a  i  per  cent,  solution 
of  osmic  acid.  Sections  are  then  maae  with  a  freezing  microtome  after 
embedding  in  gum.  No  process  must  be  used  by  which  the  fat  would 
be  dissolved  out  (Schafer).      (See  Fig.  172,  p.  435.) 

(&)  Feed  a  cat  with  30  grammes  of  butter  stained  a  deep  red  with  the 
dye  Sudan  III.  After  five  hours  anaesthetize  the  animal  with  ether, 
insert  a  cannula  in  the  carotid  artery,  and  obtain  a  sample  of  blood. 
Defibrinate  the  blood,  and  separate  the  serum  by  the  centrifuge.  If 
digestion  and  absorption  of  the  fat  have  proceeded  normally,  the 
serum  will  contain  numerous  fat  droplets,  and  will  be  tinged  pink  by 
the  dye,  which  can  be  dissolved  out  of  it  by  shaking  up  with  ether.  On 
opening  the  abdomen  it  will  be  seen  that  the  mucous  membrane  of  the 
small  intestine,  as  far  down  as  the  fat  has  reached,  is  stained  pink,  and 
that  the  lacteals  in  the  mesentery  are  also  pink.  Observe  whether  any 
of  the  pigment  has  passed  into  the  urine. 

14.*  Time  required  for  Digestion  and  Absorption  of  Various  Food 
Substances. — Feed  three  dogs,  A,  B,  and  C,  which  have  previously  fasted 
for  twenty-four  hours,  with  a  meal  containing  starch  (proved  to  be  free 
from  sugar),  lard,  and  meat. 

(i)  After  fifteen  minutes  inject  subcutaneously  into  A  2  c.c.  of  a 
O'l  per  cent,  solution  of  apomorphine.  Note  the  time  which  elapses 
before  the  animal  vomits.     Collect  the  vomit. 

[a)  Examine  a  little  of  it  under  the  microscope,  and  make  out  fat 
globules,  muscular  fibres  and  starch  granules.  The  latter  can  be  recog- 
nized by  their  being  coloured  blue  by  a  drop  or  two  of  iodine  solution. 

(b)  Filter  the  chyme,  mixing  it,  if  necessary,  with  a  little  water,  and 
test  it  as  in  8  {d)  (p.  452)  for  the  products  of  digestion  of  proteins.  In 
addition,  test  for  starch,  dextrin,  and  reducing  sugar. 

(2)  One  and  a  quarter  hours  after  the  meal  inject  apomorphine  into 
dog  B,  and  proceed  as  in  (i). 

(3)  Two  and  a  half  hours  after  the  meal  inject  apomorphine  into 
dog  C,  and  proceed  as  in  (i).  Compare  the  results  from' the  three 
specimens  of  chyme. 

15.*  Quantity  of  Cane-Sugar  inverted  and  absorbed  in  a  Given  Time. — 
Take  three  dogs.  A,  B,  and  C,  which  have  fasted  for  twenty-four  hours. 
The  animals  should  be  about  the  same  size.  Feed  A  and  B  with 
100  c.c.  of  a  standard  solution  of  cane-sugar  (about  a  20  per  cent,  solu- 
tion), or  as  much  more  as  they  will  take.  If  the  dogs  have  been  kept 
without  water  for  a  day  they  will  more  readily  take  the  sugar  solution. 
Or  it  may  be  given  through  a  tube  passed  into  the  stomach,  and  in 
this  case  a  larger  quantity  of  sugar  can  be  given.  A  gag  consisting  of 
a  piece  of  wood  with  a  hole  in  the  middle  of  it,  through  which  the  tube 
is  passed,   must  first  be  secured  in  the  dog's  mouth.     Feed  C  with 

*  Experiments  14  and  15  are  conveniently  done  in  a  class  by  assigning 
each  of  the  three  animals  to  a  separate  set  of  students.  The  contents  of  the 
stomach  and  intestine  are  divided  into  three  portions,  so  that  each  set  has 
a  sample  from  each  dog. 


PRACTICAL  EXERCISES  459 

50  grammes  of  powdered  cane-sugar  mixed  with  lard,  the  mixture  being 
rolled  into  little  balls. 

(i)  After  a  quarter  of  an  hour  put  A  under  chloroform  or  the  A.C.E. 
mixture,  and  fasten  it  on  a  holder.  Kill  the  animal  with  chloroform, 
open  the  abdomen,  tie  the  oesophagus,  place  double  ligatures  on  the 
pyloric  end  of  the  stomach  and  the  lower  end  of  the  small  intestine,  and 
divide  between  them.  Cut  out  the  stomach  and  intestine ;  wash  their 
contents  into  separate  vessels,  and  test  the  reaction  with  litmus  paper. 
Add  water  and  rub  up  thoroughly.  Filter.  Wash  the  residue  re- 
peatedly with  small  quantities  of  water,  and  pass  all  the  washings 
through  the  filter.     Make  up  each  of  the  two  filtrates  to  200  c.c. 

{a)  Test  the  filtrates  from  the  contents  of  the  stomach  and  intes- 
tines qualitatively  for  dextrose  by  Trommer's  (p.  10)  or  Fehling's 
(p.  517)  and  the  phenyl-hydrazine  test  (p.  517). 

{b)  If  no  reducing  sugar  is  present,  add  to  20  c.c.  of  each  filtrate  i  c.c. 
of  hydrochloric  acid,  boil  for  half  an  hour,  and  again  test  for  reducing 
sugar.     If  it  is  now  found,  some  cane-sugar  is  present. 

{c)  If  reducing  sugar  is  found,  estimate  its  amount  as  dextrose  by 
Fehling's  solution  (p.  518)  in  a  measured  quantity  of  the  original 
filtrate  of  the  gastric  or  intestinal  contents  before  and  after  boiling 
with  one-twentieth  of  its  volume  of  hydrochloric  acid. 

{d)  Estimate  in  the  same  way  the  amount  (as  dextrose)  of  the  invert 
sugar  in  the  standard  solution  of  cane-sugar  after  inversion,  and  before 
inversion  if  it  gives  the  qualitative  test  for  reducing  sugar  before  it  has 
been  boiled  with  acid. 

From  the  data  obtained  (and  taking  95  parts  of  cane-sugar  as  equal 
to  100  parts  of  dextrose)  calculate  the  amount  of  cane-sugar  absorbed, 
left  unchanged,  and  inverted,  though  not  absorbed. 

(2)  One  and  a  half  hours  after  the  meal  anaesthetize  B,  and  proceed 
as  in  (i). 

(3)  Two  hours  after  the  meal  proceed  in  the  same  way  with  C.  But 
in  addition  observe  the  lacteals  in  the  mesentery,  by  gently  lifting  up 
a  loop  of  intestine  immediately  after  opening  the  abdomen.  If  the 
absorption  of  the  fat  has  begun,  they  will  be  easily  visible,  as  a  network 
of  fine  milk-white  vessels.  Also  examine  the  gastric  and  intestinal 
contents  with  the  microscope  for  fat  globules.  Compare  your  results 
on  the  amount  of  sugar  obtained  from  the  three  animals.  Probably 
much  more  unabsorbed  sugar  will  be  found  in  C  than  in  B,  as  the  lard 
hinders  it  from  being  dissolved. 

16.  Auto-Digestion  of  the  Stomach. — In  some  of  the  previous  experi- 
ments the  stomach  of  an  animal  killed  during  digestion  should  be 
removed  from  the  body  after  double  ligation  of  oesophagus  and  duo- 
denum, and  placed  in  a  water-bath  at  40°  C.  After  several  hours  the 
contents  should  be  washed  out  and  the  mucous  membrane  examined. 
It  may  be  entirely  eaten  away  in  parts. 


CHAPTER  VIII 
FORMATION  OF  LYMPH 

Different  Kinds  of  Lymph. — We  ought  to  distinguish  the  lymph 
as  we  collect  it  from  the  great  lymphatic  trunks,  not  only  from  the 
liquids  of  the  serous  cavities,  but  still  more  sharply  from  the  liquid 
which  fills  the  multitudinous  clefts  and  spaces  of  the  tissues.  It  is 
now  pretty  definitely  established  that  the  tissue  spaces  do  not  com- 
municate by  actual  passages  with  the  lymphatic  vessels,  but  that 
the  latter  form  everywhere  a  closed  system  like  the  blood-vascular 
system,  the  lymph  capillaries  merely  lying  in  the  tissue  spaces 
(Sabin,  etc.).  This  conception  entails  a  radical  change  in  the 
current  views  of  lymph  production.  If  the  lymphatics  form  a 
closed  system,  the  lymph  cannot  be  actual  tissue  fluid,  but  only 
tissue  fluid  modified  by  its  passage  through  the  walls  of  the  lymph 
capillaries,  just  as  tissue  fluid  is  not  actual  blood-plasma,  but  plasma 
modified  by  its  passage  throagh  the  walls  of  the  blood  capillaries 
as  well  as  by  exchange  with  the  tissue  elements. 

Although  it  is  customary  to  speak  of  the  lymph  obtained  from 
the  lymphatic  vessels  as  if  it  were  perfectly  homogeneous,  there  is 
no  experimental  ground  for  supposing  that  the  lymph  from  different 
tracts,  or  the  tissue  liquid  in.  contact  with  the  cells  of  different 
organs,  or  even  the  tissue  liquid  in  contact  with  one  and  the  same 
cell  at  different  parts  of  its  periphery,  has  a  uniform  composition, 
or  even  a  uniform  molecular  concentration.  There  are,  indeed, 
certain  general  considerations  which  show  that  this  cannot  be  so. 
Still  less  can  it  be  assumed  that  the  serous  cavities,  although  they 
come  into  relation  with  lymphatics  and  bloodvessels  in  their  walls, 
are  analogous  to  colossal  tissue  spaces  or  even  to  expansions  of  the 
closed  lymphatic  system,  or  that  the  liquids  contained  in  them, 
normally  in  scant  amount,  are  simply  tissue,  or  if  not  tissue,  then 
simply  lymphatic  lymph.  The  cerebrospinal  fluid,  which  bathes 
the  external  surface  of  the  central  nervous  system  and  fills  its 
cavities,  and  the  special  liquids  of  the  eyeball — the  aqueous  humour 
and  the  liquid  of  the  vitreous  humour — although  no  doubt,  in 
addition  to  their  other  functions,  they  may  in  some  degree  minister 
to  the  nutrition  of  the  tissues  with  which  they  are  in  contact,  are 

460 


FACTORS  CONCERNED  IN  LYMPH  FORMATION  461 

as  regards  their  composition  and  mode  of  formation  scarcely  more 
closely  allied  to  lymph  than  sweat  is.  They  are  almost  free  from 
protein,  and  are  secreted  by  special  structures — the  choroid  plexus 
and  the  uveal  epithelium — quite  dilfcrent  from  any  that  can  bf 
concerned  in  the  formation  of  ordinary  lymph. 

It  is  very  true  these  liquids  are  not  blood,  but  that  is  scarcely  a 
sufficient  reason  for  calling  them  lymph,  else  we  might  classify 
sweat  or  even  milk  as  lymph  also.  If  a  term  is  desirable  to  indicate 
that  they  have  certain  relations  with  lymph,  they  might  perhaps 
be  spoken  of  as  lymphoid  secretions.  It  may  be  that  the  essential 
difference  in  the  chemical  composition  of  these  lymphoid  secretions 
and  lymph — the  practical  absence  of  protein — is  related  to  the 
difference  in  the  manner  of  their  formation.  The  uveal  and  choroidal 
epithelial  cells,  interposing  the  depth  of  their  columns  or  cubes 
between  the  blood  and  the  free  surface  at  which  the  liquid  escapes, 
may  well  be  suited  to  hinder  the  passage  of  the  protein  molecules 
which  find  their  way  with  greater  ease  through  the  thin  endothelium 
of  the  capillary  wall  into  the  tissue  spaces,  and  from  these  into  the 
lumen  of  the  closed  lymphatics  (see  p.  433).  Nevertheless,  we  shall 
recognize  later  on  in  the  glomeruli  of  the  kidney  an  instance  of 
blood  capillaries  but  little  pervious  to  proteins,  and  there  are  several 
other  facts  which  show  that  the  capillaries  may  differ  considerably 
in  different  organs  in  the  readiness  with  which  they  permit  the 
various  constituents  of  the  plasma  to  pass  through  their  walls. 
Further,  in  discussing  the  mechanism  by  which  lymph  is  formed, 
we  shall  see  reason  to  doubt  whether  mechanical  filtration,  due  to 
differences  of  hydrostatic  pressure  on  the  two  surfaces  of  the 
capillary  endothelium,  has  much,  if  anything,  to  do  with  the 
passage  either  of  protein  or  of  the  other  constituents  of  the  lymph 
from  the  lumen  of  the  capillaries  into  the  tissue  spaces.  At  first 
glance,  indeed,  such  a  process  would  seem  to  be  admirably  fitted  to 
explain  the  fact  that,  while  lymph  differs  but  little  from  blood- 
plasma  in  the  proportions  of  its  other  constituents,  it  is  at  most  no 
more  than  half  as  rich  in  protein.  For  there  are  many  filters  which 
allow  substances  in  ordinary  solution  and  their  solvent  to  pass 
through  without  alteration  in  their  relative  proportions,  while 
substances  like  proteins  in  colloid  solution  are  kept  back  to  a 
greater  or  less  extent. 

Factors  concerned  in  Lymph  Formation. — The  teaching  of  Ludwig, 
that  lymph  is  formed  by  the  filtration,  and  in  a  minor  degree  by  the 
diffusion,  of  the  constituents  of  blood-plasma  through  the  walls  of  the 
capillaries  into  the  tissue  spaces,  was  based  on  such  facts  as  the 
increase  in  the  tissue  liquid  of  a  limb  or  organ  which  occurs  when 
the  exit  of  blood  from  it  by  the  veins  is  hindered,  or  when  the 
quantity  of  the  circulating  liquid  is  increased  by  the  injection  of 
blood  or  salt  solution.     It  was  first  seriously  called  in  question  by 


462  FORMATION  OF  LYMPH 

Heidenhain,  who  advanced  the  theory  that  lymph  is  secreted  by 
the  endothelium  of  the  blood  capillaries.  One  of  Heidenhain's 
strongest  arguments  in  favour  of  his  secretion  theory  was  the 
existence  of  substances  which,  when  injected  into  the  blood,  in- 
creased the  flow  of  lymph  from  the  thoracic  duct  of  the  dog  without 
affecting  appreciably  the  arterial  pressure.  He  divided  these  so- 
called  lymphagogues  into  two  classes:  (i)  Substances  like  peptone, 
extracts  of  the  head  and  liver  of  the  leech,  extract  of  crayfish 
muscle,  egg-albumin,  etc.,  which  cause  not  only  an  increase  in  the 
rate  of  flow,  but  an  increase  in  the  specific  gravity  and  total  solids 
of  the  lymph;  (2)  crystalloid  substances,  like  sugar,  salt,  etc.,  which 
cause  an  increased  flow  of  lymph  more  watery  than  normal. 

Starling  has  shown  that,  although  the  lymphagogues  of  the  second 
class  do  not  raise  the  arterial  pressure,  they  do,  by  attracting  water 
from  the  tissues  and  thus  causing  hydraemic  plethora  (an  excess  of 
blood  of  low  specific  gravity),  bring  about  a  marked  rise  of  venous, 
and  therefore,  what  is  the  important  thing  for  lymph  filtration,  of 
capillary  pressure.  But  it  can  be  demonstrated  that  vaso-dilata- 
tion  with  increase  of  capillary  pressure  is  not  in  itself  sufficient  to 
increase  the  formation  of  lymph.  We  have  seen,  e.g.  (p.  177),  that 
when  the  chorda  tympani  nerve  is  stimulated  in  the  dog  the  arteri- 
oles of  the  submaxillary  gland  are  dilated,  and  no  doubt  the  pres- 
sure in  the  capillaries  is  increased.  No  increased  flow  of  lymph, 
however,  takes  place  from  the  submaxillary  lymphatics  during  even 
prolonged  excitation  of  the  chorda,  nor  do  the  lymph  spaces  of  the 
gland  become  distended  (Heidenhain).  In  the  horse  also  the  spon- 
taneous flow  of  lymph  from  the  quiescent  parotid  is  not  appreciably 
altered  by  excitation  of  the  secretory  nerves  of  the  gland  or  by 
pilocarpine  (Carlson).  There  is  every  reason  to  believe  that  during 
active  secretion  of  saliva  tissue  liquid  is  really  formed  from  the 
blood  in  increased  amount,  and  that  it  is  from  the  tissue  spaces 
that  the  gland-cells  directly  obtain  the  increased  supply  of  water 
and  other  substances  necessary  to  sustain  the  increased  secretion. 
But  a  balance  is  maintained  between  the  production  of  tissue  liquid 
and  its  removal  by  the  gland-cells.  When  the  gland  is  quiescent, 
the  small  amount  of  tissue  liquid  normally  formed  from  the  blood 
capillaries  for  the  nutrition  of  the  cells  is  balanced  by,  upon  the 
whole,  an  equal  amount  of  lymph  secreted  from  the  tissue  spaces 
into  the  lymph  capillaries. 

We  may  say,  indeed,  that  the  closed  lymphatic  system  has  for 
its  great  function  the  regulation  of  the  quantity  and  quality  of  the 
tissue  liquid.  In  glands  with  an  external  secretion  increased  irriga- 
tion of  the  tissue  spaces  from  the  blood  does  not  as  a  rule  lead  to 
increased  flow  of  lymph,  because  the  surplus  fluid  is  required  to 
form  the  secretion.  In  other  organs,  however,  such  as  the  muscles 
and  the  ductless  glands,  it  is  probable  that  the  augmented  irriga- 


FACTORS  CONCERNED  IN  LYMPH  FORMATION  463 

tion  rendered  necessary  by  functional  activity  is  always  associated 
with  an  accelerated  flow  of  lymph,  which  carries  off  the  surplus 
liquid,  including  a  portion  of  the  waste  products.  It  is  probable 
that  an  important  factor  in  the  production  of  adema  may  be  the 
derangement  of  the  mechanism,  whatever  it  is,  through  which  the 
adjustment  of  the  rate  of  formation  of  tissue  liquid  to  that  of 
lymphatic  lymph  is  achieved.  But  it  must  be  remembered  that  in 
all  the  organs  the  blood  capillaries  not  only  supply  materials  to  the 
tissue  spaces,  but  take  up  materials  from  them.  Indeed,  there  are 
facts  which  indicate  that  in  general  water  and  dissolved  substances 
pass  more  easily  and  in  greater  amount  back  from  the  tissues  into 
the  blood  than  into  the  lymphatics.  So  that,  while  the  lymphatics 
constitute  an  accessory  drainage  system,  the  bloodvessels  irrigate 
the  tissues  and  drain  them  as  well.  A  consequence  of  this,  as  well 
as  of  the  great  difference  in  the  capacity  of  the  different  tissues  for 
storing  water,  is  that  the  amount  of  tissue  lymph  formed  can  never 
be  estimated  from  the  amount  of  lymphatic  lymph  leaving  an  organ. 
Thus  the  flow  of  Ij^mph  from  the  limbs  at  rest  is  very  small  in  com-' 
parison  with  the  flow  from  the  abdominal  viscera,  which  constitutes 
the  great  bulk  of  the  lymph  passing  along  the  thoracic  duct.  This, 
however,  does  not  prove  that  very  little  liquid  passes  out  of  the 
limb  capillaries,  for  the  chief  tissue  of  the  limbs,  the  muscles,  pos- 
sesses a  far  greater  storage  capacity  for  water  than  the  intestines  and 
digestive  glands.  In  the  one  case  we  have  a  field  whose  soil  takes 
up  a  great  deal  of  water  and  is  not  easily  saturated;  in  the  other  a 
field  whose  soil  soon  becomes  water-logged  and  refuses  to  take  up 
any  more.  With  the  same  supply  from  the  irrigating  ditch,  little 
or  no  water  may  drain  off  at  the  foot  of  the  first  field,  a  great  deal 
at  the  foot  of  the  second. 

Where  the  main  lymphatics  are  themselves  blocked  by  mechanical 
pressure  or  by  inclusion  in  a  ligature,  the  balance  is,  of  course, 
grossly  upset  by  the  failure  of  the  outflow  of  lymph  to  keep  pace 
with  its  formation.  Where  an  obstruction  on  the  course  of  the 
veins  is  responsible  for  the  oedema,  the  lymphatic  outflow,  to  be 
sure,  is  not  directly  interfered  with.  But  the  nutrition  and  the 
respiration  of  the  vascular  walls  themselves,  including  the  endo- 
thelium of  the  capillaries,  necessarily  suffers  from  the  insufiiciency 
of  the  blood-flow,  and  the  crippled  capillaries  may  very  well  become 
abnormally  permeable  for  water,  salts,  and  the  other  constituents 
of  lymph.  And  while  ordinary  mechanical  filtration  may  not  be  a 
factor,  or  a  very  unimportant  one,  in  the  passage  of  liquid  through 
the  normal  capillary  wall,  it  may  become  far  more  effective  when 
it  acts  on  a  damaged  wall.  The  tissue  cells  also  suffer  from  lack 
of  oxygen  and  nutritive  material,  and  from  the  accumulation  of 
waste  products,  including  acid  substances,  which  cause  them  to 
take  up  and  to  hold  more  water  than  normal.     Even  in  the  absence 


464  FORMATION  OF  LYMPH 

of  changes  in  the  mechanical  conditions  of  the  blood  and  lymph 
circulations,  alterations  in  the  tissues  must  be  recognized  as  among 
the  causes  of  oedema  (Fischer).  Thus  it  is  clear  that  the  interpre- 
tation of  such  an  apparently  simple  experiment  as  the  production 
of  oedema  by  the  ligation  of  a  vein  needs  great  care.  Whatever  it 
proves,  it  may  be  said  with  confidence  that  it  does  not  prove  that 
the  increased  capillary  pressure  is  the  direct  cause  of  the  oedema. 

A  mere  increase  in  the  capillary  blood-pressure  does  not  of  itself 
accelerate  the  formation  of  tissue  liquid  from  the  blood  any  more 
than  that  of  lymph  from  the  tissue  liquid,  as  is  shown  by  the  fact 
that,  when  the  chorda  tympani  is  stimulated  after  injection  of  a 
dose  of  atropine  sufficient  to  prevent  all  salivary  secretion,  there  is 
neither  oedema  of  the  gland  nor  increase  in  the  flow  of  lymph  from 
it,  although  the  arterioles  are  as  widely  dilated  as  before.  When  the 
blood-pressure  is  greatly  increased  in  the  anterior  portion  of  an 
animal  by  clamping  the  aorta,  or  in  the  whole  animal  by  continued 
stimulation  of  the  cut  medulla  oblongata  or  the  splanchnic  nerves, 
the  blood  does  not  alter  in  concentration  in  the  least,  showing  that 
no  sensible  increase  in  the  passage  of  water  into  the  lymph  has 
occurred.  After  division  or  embolism  of  the  medulla  oblon- 
gata, and  consequent  paralysis  of  the  vaso-motor  centre  and 
general  vascular  dilatation,  it  is  stated  that  the  injection  of  sodium 
chloride  produces  an  increase  in  the  lymph-flow  as  great  and  as 
durable  as  in  the  normal  animal,  and  which  can  continue  even  after 
death  (Pugliese).  The  action  of  the  first  class  of  lymphagogues, 
which  cannot  be  explained  as  the  consequence  of  an  increase  of 
capillary  pressure,  because  the  pressure  in  the  capillaries  is  not 
consistently  increased,  and  may  even  in  the  case  of  some  of  these 
lymphagogues  be  diminished,  is  attributed  by  Starling  to  an  injurious 
effect  on  the  capillary  endothelium  (and  especially  on  the  endo- 
thelium of  the  capillaries  of  the  liver,  since  nearly  the  whole  of  the 
increased  lymph-flow  comes  from  that  organ),  which  increases  its 
permeability.  But  it  is  not  easy  to  distinguish  an  increase  of  per- 
meability produced  by  lymphagogues  from  an  increase  of  secretory 
activity  of  the  endothelial  cells. 

Hamburger,  too,  has  brought  forward  results  which  it  is  difficult 
to  reconcile  with  a  theory  of  filtration  even  for  the  second  class  of 
lymphagogues.  Further,  Heidenhain  has  shown  that  some  time 
after  injection  of  a  crystalloid  substance,  like  sugar,  into  the  blood, 
a  greater  percentage  of  the  substance  may  be  found  in  the  lymph 
than  in  the  blood.  Now,  when  a  mixture  of  crystalloids  and  col- 
loids is  filtered  through  a  thin  membrane,  the  percentage  of  crystal- 
loids in  the  filtrate  is  never,  at  most,  greater  than  in  the  original 
liquid.  And  although  Cohnstein  states  that,  if  time  enough  be 
allowed,  the  maximum  concentration  of  sodium  chloride  in  the 
lymph,    after   intravenous  injection,    becomes   approximately   the 


FACTOnS  CONCERNED  IN  LYMPH  FORMATION  465 

same  as  the  maximum  in  the  blood,  this  fact  loses  its  weight  as 
an  argument  in  favour  of  the  filtration  hypothesis  when  we  re- 
member that,  according  to  Asher,  all  the  solids  of  the  lymph  are 
markedly  increased  when  even  small  quantities  of  crystalloids  are 
injected  into  the  veins.  Upon  the  whole,  then,  it  may  be  con- 
cluded that  up  to  the  present  it  has  not  been  shown  that  filtration 
due  to  the  excess  of  pressure  in  the  capillaries  over  that  in  the 
lymph  spaces  is  an  effective  factor  in  the  formation  of  lymph.  Nor 
is  it  at  all  easier  to  explain  lymph  formation  as  a  matter  of  pure 
osmosis  or  diffusion.  Lazarus-Ba,rlow  found,  for  example,  that  in 
the  great  majority  of  his  experiments  the  injection  of  a  concen- 
trated solution  of  sodium  chloride,  dextrose  or  urea  into  a  vein  was 
followed,  not  by  an  initial  diminution  in  the  outflow  of  lymph  (as 
might  have  been  expected  if  the  exchange  of  water  between  the 
blood  and  the  tissue  spaces,  and  between  the  tissue  spaces  and  the 
lymph  capillaries,  was  regulated  solely  by  differences  in  osmotic 
pressure),  but  by  an  immediate  increase.  And  Carlson  has  shown 
that  the  osmotic  pressure  of  lymph  coming  from  the  active  salivary 
glands,  as  measured  by  the  freezing-point  method,  may,  under 
chloroform  or  ether  anaesthesia,  be  distinctly  less  than  that  of  the 
blood-serum.  Water  must  therefore  be  passing  from  a  liquid  of 
higher  to  one  of  lower  osmotic  concentration. 

Nevertheless,  it  would  be  erroneous  to  assume  that  because 
osmosis  and  diffusion  have  not  been  shown  to  satisfactorily  account 
for  all  the  phenomena  of  lymph  formation,  they  exert  no  influence 
upon  it.  It  is  probable,  indeed,  that  their  action  is  fully  as  im- 
portant as  in  absorption  from  the  alimentary  canal,  although,  as  in 
absorption,  it  is  often  overlaid  and  always  modified  by  the  specific 
permeability  of  the  blood-capillary  walls,  the  lymph-capillary  walls, 
and  the  tissue  cells  in  general,  in  virtue  of  which  they  exert  an 
action  upon  the  quantity  and  composition  of  the  lymph  analogous 
to  the  action  exerted  in  a  higher  degree  by  the  cells  of  the  digestive 
glands  upon  the  quantity  and  composition  of  the  liquids  passing 
into  their  ducts. 

It  is  not  difficult  to  ilhistratc  the  fact  that  phenomena  of  osmosis  and 
diffusion  emerge,  altliough  not  of  course  in  such  purity  as  in  physical 
experiments,  when  we  study  the  interchange  between  the  blood  and 
the  tissue  liquids.  If,  for  example,  a  hypertonic  solution  of  sodium 
chloride  is  injected  into  the  blood,  water  rapidly  passes  from  the  tissues 
to  the  blood  as  it  would  through  a  semipermeable  membrane,  and  the 
blood  becomes  diluted.  At  the  same  time  sodium  chloride  leaves  the 
blood  and  passes  into  the  tissues,  as  it  would  do  by  diffusion  from  a 
place  of  higher  to  a  place  of  lower  concentration.  But  after  this  has 
gone  on  for  some  time,  and  the  concentration  of  the  blood  in  salt  has 
sunk,  it  may  be,  to  that  in  the  lymph,  salt  still  continues  to  pass  out 
of  the  blood,  and  the  excess  of  water  also  leaves  the  bloodvessels  till  the 
osmotic  pressure  of  the  blood  has  again  become  normal.  When  isotonic 
and  even  hypotonic  solutions  of  sodium  chloride  arc  injected,  salt  also 

30 


466  FORMATION  OF  LYMPH 

leaves  the  blood  and  enters  the  lymph,  although  it  ought  not  to  do  so 
by  diffusion,  while  water,  which  might  pass  from  th:  hypotonic  blood 
into  the  lymph  by  osmosis,  moves  in  the  same  direction  from  the  blood 
to  which  the  isotonic  salt  solution  has  been  added.  Regulative  mechan- 
isms, in  short,  exist  which  tend,  with,  but  also  without,  the  co-opera- 
tion of  diffusion  and  osmosis,  and  even,  so  to  say,  in  their  teeth, 
to  bring  back  the  quantitative  and  qualitative  composition  of  the 
blood  to  the  normal.  Exactly  similar  phenomena  are  witnessed  when 
ths  equilibrium  is  upset  from  the  other  side  by  the  injection  of  salt 
solutions  into  the  subcutaneous  tissue  or  the  intramuscular  connective 
tissue.  Hypotonic  sodium  chloride  solution  injected  into  the  sub- 
conjunctival connective  tissue  quickly  loses  water  and  gains  sodium 
chloride,  as  it  ought  to  do  if  under  the  influence  of  osmosis  and  diffusion, 
and  hypertonic  salt  solutions  gain  wat^r.  But  eventually  hypertonic, 
hypotonic,  and  isotonic  solutions,  and  even  serum  itself,  are  completely 
absorbed,  which  could  not  occur  in  the  presence  of  diffusion  and 
osmosis  alone.  Sometimes  in  dropsy  it  appears  that  the  oedema  liquid 
is  absorb  d  when  the  patient  is  put  on  a  diet  free  as  far  as  possible 
from  salts.  The  suggestion  is  that  the  regulative  mechanism  which 
tends  to  keep  the  molecular  concentration  of  the  blood  and  lymph 
approximately  constant  provides  that  as  the  salt  content  of  the  body 
falls,  which  it  does  through  continued  excretion  of  salts  in  the  urine, 
water  is  eliminated  in  corresponding  amount. 

The  Contribution  of  the  Tissue-Cells  to  the  Lymph. — So  far  we 
have  considered  the  passage  of  the  lymph  constituents,  on  the  one 
hand  through  the  endothehum  of  the  blood  capiharies  into  the 
tissue  spaces;  on  the  other,  from  the  tissue  spaces  through  the  endo- 
thehum of  the  lymph  capillaries.  But  it  is  not  to  be  supposed  that 
the  liquid  lying  in  clefts,  partly  bounded  by  blood  capillaries,  partly 
by  lymph  capillaries,  partly  by  tissue-cells,  should  be  affected  solely 
by  the  first  two.  The  third  anatomical  element  must  contribute 
something  to,  or  withdraw  something  from,  the  tissue  liquid,  and 
may  thus  play  a  part  in  the  formation  of  lymph  from  the  latter. 
The  recent  researches  of  Asher  and  his  pupils  have  raised  the  ques- 
tion of  the  relation  be1>ween  the  physiological  activity  of  the  organs, 
and  especially  of  the  glands,  and  the  formation  of  the  lymph.  They 
conclude  that  the  common  doctrine  that  lymph  is  simply  a  diluted 
blood-plasma  is  erroneous.  Lymph,  they  say,  far  from  being  a 
mere  filtrate  or  even  a  secretion  from  the  blood,  is  formed  by  the 
activity  of  the  organs,  and  may  actually  be  absorbed  by  the  blood 
from  the  ti.ssue  spaces.  In  fact,  according  to  their  view,  the  in- 
travenous injection  of  lymphagogues,  both  crystalloid  and  colloid, 
only  causes  an  increased  flow  of  lymph  in  so  far  as  it  leads  to  in- 
creased glandular  secretion.  But  this  generalization  has  had  only 
a  short-lived  vogue,  and  one  by  one  some  of  the  main  results  which 
seemed  to  support  it  have  been  disproved  or  shown  to  be  capable 
of  interpretation  in  a  different  sense.  For  example,  it  was  stated 
that  secretin  causes  a  flow  of  lymph  from  the  lymphatics  of  the 
pancreas,  as  well  as  a  flow  of  pancreatic  juice.  But  it  has  been 
shown  that  the  increased  production  of  lymph  is  not  due  to  the 


INFLUENCE  OF  NERVES  ON  LYMPH  FORMATION         467 

secretin  at  all,  but  to  lymphagogue  substances,  including  proteose, 
extracted  with  the  secretin  from  the  intestinal  mucous  membrane. 
A  solution  of  secretin  can  be  prepared  which  causes  a  considerable 
increase  in  the  secretion  of  pancreatic  juice  and  bile,  but  no  augmen- 
tation whatever  in  the  flow  of  lymph  from  the  thoracic  duct. 
Again,  it  was  asserted  that  peptone,  a  noted  lymphagogue,  produces 
a  great  increase  in  the  biliary  secretion.  It  has  been  demonstrated, 
however,  that  the  action  of  the  peptone  is  merely  to  cause  expul- 
sion of  the  contents  of  the  gall-bladder  by  the  mechanical  effect  of 
the  swelling  of  the  liver,  and  not  at  all  to  stimulate  the  liver-cells 
to  form  more  bile.  For  it  produces  no  effect  on  the  flow  of  bile 
if  the  gall-bladder  be  emptied  or  the  cystic  duct  tied  before  the 
injection  (Ellinger).  That  active  salivary  secretion  is  not  accom- 
panied by  increased  lymph-flow  from  the  lymphatics  of  the  salivary 
glands  has  been  mentioned  above.  Nevertheless,  we  may  safely 
assume  that  the  activity  of  the  organs  does  make  a  contribution  to 
the  lymph — to  its  solids,  if  not  in  any  important  degree  to  its  water- 
content,  although  to  say  that  they  alone  are  concerned  in  its  forma- 
tion, to  the  exclusion  of  the  capillaries,  is  altogether  an  over-state- 
ment. The  waste-products  of  the  tissues  pass  into  the  lymph,  and 
possibly,  as  Koranyi  suggests,  may,  by  increasing  its  molecular 
concentration,  cause  the  passage  of  some  water  into  it  from  the 
blood.  Or  the  decomposition  of  the  large  protein  molecules,  which 
in  tissue  metabolism  are  breaking  down  into  numerous  smaller 
molecules,  may  entail  an  increase  of  osmotic  pressure  in  the  cells 
themselves,  which  in  turn  may  lead  to  withdrawal  of  water  by  the 
cells  from  the  tissue  liquid.  The  osmotic  pressure  of  the  liquid 
may  thus  rise,  and  water  may  pass  into  the  tissue  spaces  from  the 
blood.  The  molecular  concentration  of  lymph  (except  in  anaesthe- 
tized animals  as  mentioned  above)  is  in  general  somewhat  greater 
than  that  of  blood-serum — e.g.,  in  one  observation  A  of  serum 
was  0605°  C,  and  of  lymph  o-6io°  C.  For  the  solid  tissues,  the 
freezing-point  of  which,  however,  cannot  be  as  satisfactorily  deter- 
mined as  that  of  liquids,  the  following  values  of  A  were  obtained: 
Brain,  065°;  muscle,  068°;  kidney,  094°;  liver,  0-97°;  while  for 
blood  it  was  0-57°  (Sabbatani). 

To  Slim  up,  we  may  say  that  while  the  physical  processes  of  filtra- 
tion, osmosis  and  diffusion  may  play  a  part  in  the  passage  of  water 
and  solids  through  the  walls  of  the  blood  capillaries,  as  well  as  from 
the  tissue-cells  into  the  tissue  spaces,  and  from  these  spaces  into  the 
lymph  capillaries,  there  is  much  ivhich  they  leave  unexplained,  and 
which  at  present,  for  the  want  of  a  more  precise  term,  we  must  attribute 
to  secretory  activity. 

Influence  of  Nerves  on  Lymph  Formation. — In  one  instance 
it  appears  to  have  been  shown  that  lymph  may  be  formed 
under  the  influence  of  secretory  nerves.     In  the  males  of  certain 


468  FORMATION  OF  LYMPH 

aquatic  birds  erection  is  due  to  the  filling  of  the  corpus  cavernosum, 
not  with  blood,  but  with  lymph.  The  lymph  is  secreted  rapidly  by 
the  so-called  bodies  of  Tannenberg  when  certain  sympathetic  nerve- 
fibres  are  experimentally  stimulated,  and  passes  into  the  corpus 
cavernosum,  which  swells  up.  If  a  small  incision  is  made  in  the 
corpus,  a  large  quantity  of  clear  lymph,  which  clots  slowly  on  stand- 
ing, escapes.  There  is  a  simultaneous  vasodilatation.  After  erection, 
the  lymph  is  rapidly  and  completely  reabsorbed  (Eckhard,  Miiller). 

Although  no  definite  lymph-secretory  nerve-fibres  have  as  yet 
been  discovered  in  mammals  and  for  ordinary  tissues,  it  is  possible 
that  they  exist  (Sihler).  As  already  pointed  out,  the  same  volume 
of  liquid  as  escapes  into  the  ducts  of  the  active  submaxillary  gland 
must,  upon  the  whole,  pass  out  of  the  blood  capillaries.  On  what 
principle  shall  we  distinguish  one  only  of  these  processes  as  physio- 
logical secretion  ?  They  begin  together  when  the  chorda  tympani 
is  stimulated.  A  drug  which  paralyzes  secretory  nerve-endings 
abolishes  both  effects.  The  simplest  explanation  is  that  the  chorda 
contains  secretory  fibres  which  influence  the  formation  both  of 
saliva  and  of  the  tissue  liquid  from  which  it  is  recruited;  and,  so 
far  as  this  consideration  goes,  it  is  just  as  logical  to  consider  the 
increase  in  the  supply  of  tissue  liquid  as  the  cause  of  the  increase 
in  the  flow  of  saliva  as  to  consider  the  increased  salivary  secretion 
as  the  cause  of  the  increased  flow  of  liquid  into  the  tissue  spaces. 
The  increased  flow  of  liquid  may  be  brought  about  either  by  an 
action  of  the  nerve  on  the  gland-cells,  causing  them  to  produce  a 
hormone,  which  then  effects  the  blood  capillaries  (Carlson),  or  by 
a  direct  action  on  the  capillary  endothelium.  The  advantage  to 
cells  engaged  in  the  active  secretion  of  saliva  of  being  immersed  in 
an  abundant  bath  of  tissue  liquid  is  obvious. 

The  post-mortem  flow  of  lymph,  which  may  continue  in  some 
cases  long  after  complete  cessation  of  the  circulation — for  an  hour 
after  injection  of  dextrose  to  produce  hydraemic  plethora;  for  as 
much  as  four  hours  after  injection  of  extract  of  the  strawberry, 
which  is  a  lymphagogue  of  Heidenhain's  first  group  (Mendel  and 
Hooker) — is  a  phenomenon  whose  relation  to  normal  lymph  forma- 
tion has  not  been  definitely  settled. 

It  ought  to  be  remembered  in  this  whole  discussion  that  the 
epithelium  of  ordinary  glands  derives  its  supplies  of  material  from 
the  tissue  lymph.  The  vicissitudes  of  blood-pressure  affect  it  only 
in  a  secondary  and  indirect  manner.  On  the  other  hand,  the  endo- 
thelial cells  of  the  capillaries  are  in  direct  contact  with  the  blood. 
And  it  is  interesting  to  observe  that  in  this  respect  the  glomeruli 
of  the  kidney  and  the  alveoli  of  the  lungs  (if  the  endothelial  lining 
of  Bowman's  capsule  and  the  alveolar  membrane  are  assumed  to 
be  complete)  take  a  middle  place  between  the  glands  proper  and 
the  quasi-glandular  capillaries. 


CHAPTER    IX 
EXCRETION 

We  have  now  followed  the  ingoing  tide  of  gaseous,  liquid,  and  solid 
substances  within  the  physiological  surface  of  the  body.  There  we 
leave  them  for  the  present,  and  turn  to  the  consideration  of  the 
channels  of  outflow,  and  the  waste  products  which  pass  along  them. 
In  a  body  which  is  neither  increasing  nor  diminishing  in  mass  the 
outflow  must  exactly  balance  the  inflow;  all  that  enters  the  body 
must  sooner  or  later,  in  however  changed  a  form,  escape  from  it 
again.  In  the  expired  air,  the  urine,  the  secretions  of  the  skin,  and 
the  faeces,  by  far  the  greater  part  of  the  waste  products  is  elimin- 
ated. Thus  the  carbon  of  the  absorbed  solids  of  the  food  is  chiefly 
given  off  as  carbon  dioxide  by  the  lungs;  the  hydrogen,  as  water 
by  the  kidneys,  lungs  and  skin,  along  with  the  unchanged  water 
of  the  food;  the  nitrogen,  as  urea  by  the  kidneys.  The  fseces  in 
part  represent  unabsorbed  portions  of  the  food.  A  small  and 
variable  contribution  to  the  total  excretion  is  the  expectorated 
matter,  and  the  secretions  of  the  nasal  mucous  membrane  and 
lachrymal  glands.  Still  smaller  and  still  more  variable  is  the  loss 
in  the  form  of  dead  epidermic  scales,  hairs,  and  nails.  The  dis- 
charges from  the  generative  organs  are  to  be  considered  as  excre- 
tions with  reference  to  the  parent  organism,  and  so  is  the  milk,  and 
even  the  foetus  itself,  with  respect  to  the  mother. 

Excretion  by  the  lungs  and  in  the  faeces  has  been  already  dealt 
with.  All  that  is  necessary  to  be  said  of  the  expectoration  and 
the  nasal  and  lachrymal  discharges  is  that  the  first  two  generally 
contain  a  good  deal  of  mucin,  and  are  produced  in  small  mucous 
and  serous  glands,  the  cells  of  which  are  of  the  same  general  type 
as  those  of  the  mucous  and  serous  salivary  glands.  The  lachrymal 
glands  are  serous  like  the  parotid;  and  the  tears  secreted  by  them 
contain  some  albumin  and  salts,  but  little  or  no  mucin.  The  sexual 
secretions  and  milk  will  be  best  considered  under  reproduction 
(Chap.  XIX.),  so  that  there  remain  only  the  urine  and  the  secre- 
tions of  the  skin  to  be  treated  here. 

4G9 


470  EXCRETION 


Section  I. — Excretion  by  the  Kidneys — The  Chemistry  of 

THE  Urine. 

Normal  urine  is  a  clear  yellow  liquid  acid  to  litmus  and  similar 
indicators,  but  nearly  neutral  or  very  weakly  acid  in  the  physico- 
chemical  sense  (p.  24).  The  average  specific  gravity  is  about  1020, 
the  usual  limits  being  1015  and  1025,  although  when  water  is  taken 
in  large  quantities,  or  long  withheld,  the  specific  gravity  may  fall 
to  1005,  or  even  less,  or  rise  to  1035,  or  even  more.  The  quantity 
passed  in  twenty-four  hours  is  very  variable,  and  is  especially 
dependent  on  the  activity  of  the  sweat-glands,  being,  as  a  rule, 
smaller  in  summer  when  the  skin  sweats  much,  than  in  winter  when 
it  sweats  little.  The  average  quantity  for  an  adult  male  is  1,200  to 
1,600  CO.  (say,  40  to  50  oz.).* 

Composition  of  Urine. — This  is  very  closely  related  to  the  quantity 
and  quality  of  the  food.  Hence  it  is  impossible  to  speak  of  a 
definite  normal  composition  of  the  urine.  It  is  essentially  a  solu- 
tion of  urea  and  inorganic  salts,  the  proportion  of  the  latter  being 
generally  about  1-5  per  cent.,  or  double  the  usual  amount  of  physio- 
logical liquids.  Besides  urea,  there  are  other  nitrogenous  bodies 
in  much  smaller  quantity,  such  as  ammonia,  uric  acid,  and  the 
allied  purin  bases,  hippuric  acid,  and  kreatinin.  Some  of  these  at 
least  are  products  of  the  metabolism  of  proteins  within  the  tissues. 
And  besides  the  inorganic  salts  there  are  certain  organic  bodies — 
indoxyl,  phenyl,  pyrokatechin,  skatoxy] — united  with  sulphuric 
acid,  which  are  primarily  derived  from  the  products  of  the  putre- 
faction of  proteins  within  the  digestive  tube. 

Folin  has  published  analyses  of  '  normal '  urines  from  six  persons, 
weighing  from  56'6  to  70-9  kilos  (average  63-4  kilos),  who  were  kept 
for  seven  days  on  one  standard  uniform  diet.  The  diet  consisted  of 
500  c.c.  of  milk,  300  c.c.  of  cream  (containing  18  to  22  per  cent,  of  fat), 
450  grammes  of  eggs,  200  grammes  of  Horlick's  malted  milk,  20  grammes 
of  sugar,  6  grammes  of  sodium  chloride,  water  enough  to  make  the 
whole  up  to  two  litres,  and  900  c.c.  of  additional  water.  The  ingredients 
contained  119  grammes  of  protein,  about  148  grammes  of  fat,  and 
225  grammes  of  carbo-hydrates.  The  average  results  of  all  the  deter- 
minations are  given  in  the  following  table : 

*  The  average  quantity  of  urine  varies  not  only  with  the  season,  but  also 
with  the  habits  of  the  person,  especially  as  regards  the  amount  of  liquid 
taken.  The  average  for  seventeen  healthy  (American)  students,  whose  urine 
was  collected  for  six  to  eight  successive  days  in  winter,  was  1,166  c.c.  The 
highest  average  in  any  one  individual  for  the  observation  period  was  1,487  c.c. 
(for  seven  days),  and  the  lowest  743  c.c.  (for  eight  days).  The  greatest  quan- 
tity passed  in  any  one  period  of  twenty-four  hours  was  2,286  c.c.  (by  the  in- 
dividual whose  average  was  the  highest).  The  smalle.st  quantity  passed  in 
twenty-four  hours  was  650  c.c.  (by  the  individual  whose  average  was  the 
lowest. 


EXCRETION  BY  THE  KIDNEYS 


471 


Grnmmes. 

Containing 

Nitrogen 

(Grammes). 

Percent.ige    ■ 
of  Total 
Nitrogen. 

Urea  ----- 
Ammonia        -             -             -             - 
Kreatinin        .              -              -              _ 
Uric  acid         -              -              -              - 
Nitrogen  in  other  compounds 

29-8 

1-55 
0-37 

13-9 
0-70 
0-58 

0-I2 

0'6o 

87-5 

4-3 
3.6 
0-8 
3-75 

Total  nitrogen         -             -             - 

—        I     i6-oo 

— 

Inorganic  SO..,              .             -             . 
Ethereal  SO.,  -             -             -             - 
'  Neutral '  SO3 

Total  sulphur  as  SO3 

Total  phosphates  as  P^O-    - 
Chlorine      -              -              -              - 

2-92 

0"22 

0'i7 
3-31 

3-87 
6-1 

PcTceiila^e  of  Total 
Sulphur, 

87-8 

6-8 
5-1 

Titratable  acidity  in  c.c.  of  decinormal  acid  -  617  ]  ^^tranir '  fro 

(^organic,  3^3" 


Indican  (Fehling's  solution  = 
Volume  of  urine 


77 
1430  c.c. 


The  great  influence  of  diet  on  the  composition  of  the  urine  is  illus- 
trated in  the  following  table.  Urine  I.  was  obtained  from  a  man  weigh- 
ing 87  kilos  on  the  standard  protein-rich  diet  described  above.  Urine  II. 
was  obtained  from  the  same  person  on  a  diet  very  poor  in  protein 
(400  grammes  of  starch  and  300  c.c.  of  cream),  containing  only  about 
I  gramme  of  nitrogen,  as  against  19  grammes  in  the  first  diet. 


I. 

II 

Volume  of  urine 

1170 

c.c. 

1 
385  c.c.           1 

t 

Grammes. 

Per  Cent. 

Grammes. 

Per  Cent. 

Total  nitrogen   -             -             - 

i6-8 

3-60 

1   Urea-nitrogen     -              -              - 

1470   = 

87-5 

2 -20     = 

61-7 

Ammonia-nitrogen 

0-49   = 

3-0 

0'42     = 

1 1 -3 

Uric  acid-nitrogen 

o-i8   = 

i-i 

0-09    = 

2-5 

Kreatinin-nitrogen 

0-58   = 

3-6 

0'6o    = 

17-2 

1  Nitrogen  in  other  compounds    - 

0-85   = 

4-9 

0-27    = 

7-3 

Total  SO3            -             -             - 

3-64 

Inorganic  SO3     -             -             - 

3-27   = 

90-0 

0-46    = 

60-5 

Ethereal  SO., 

0-19   = 

5-2 

o-io   = 

13-2 

Neutral  SO., 

o-i8  = 

4-8 

0'20    = 

26-3 

Total  phosphates  as  P2O5 

4-1 

I-O 

Chlorine               .             .             - 

6-1 

1-6 

Titratable  acidity  in  c.c.       axid 
Indican  (Fehling's  solution  =  100) 


g   .  (  mineral,  398     ^    (  mineral,  123. 
•^  Inorganic,  407  ^"^  (^organic,  201 


♦  The  indican  is  given  in  arljitrary  units,  the  indigo  blue  being  obtained 
from   the  urine  and  then  estimated   colorimctrically,   using  Fehling's  solu- 


472 


EXCRETION 


The  titrable  acidity  of  urine  (sec  p.  25)  is  chiefly  due  to  the  acid  (mono- 
basic) phosphates,  such  as  acid  sodium  phospliate  (NaH2P04),  but  in 
an  important  degree  also  to  organic  acids.  According  to  Folin,  indeed, 
the  organic  acidity  may  be  more  than  half  the  total  acidity.  Normally 
the  acidity  diminishes  distinctly,  or  even  gives  place  to  alkalinity, 
during  digestion,  when  the  acid  of  the  gastric  juice  is  being  secreted. 
This  is  sometimes  fancifully  denominated  the  alkaline  tide.  After  a 
fast,  as  before  breakfast,  the  opposite  condition,  the  acid  tide,  occurs. 

The  acidity  varies  with  the  quantity  oi  vegetable  food  in  the  diet. 
The  urine  of  herbivora  and  vegetarians  is  alkaline,  and  is  either  turbid 
when  passed,  or  on  standing  soon  becomes  turbid  from  precipitated 
carbonates  and  phosphates  of  earthy  bases,  while  that  of  carnivora 
and  of  fasting  herbivora,  which  are  living  on  their  own  tissues,  is 
strongly  acid  and  clear.  Normal  human  urine  may  deposit  urates  soon 
after  discharge,  as  they  are  more  soluble  in  warm  than  in  cold  water. 
They  carry  down  some  of  the  pigment,  and  therefore  usually  appear  as 
a  pink  or  brick-red  sediment.  When  urine  is  allowed  to  stand  after 
being  voided,  what  is  generally  described  as  '  acid  fermentation  '  occurs. 
The  acidity  gradually  increases;  acid  sodium  urate  is  produced  from 
the  neutral  urate,  and  comes  down  in  the  form  of  amorphous  granules, 
while  the  liberated  uric  acid  is  deposited  often  in  '  whetstone  '  crystals, 
coloured  yellow  by  the  pigment  (Fig.  177).     Calcium  oxalate  may  also 


Fig.  177. — Uric  Acid. 


Fig.   178. — Calcium  Oxalate 


be  thrown  down  as  '  envelope,'  a,  b,  or  less  frequently,  '  sand-glass  ' 
crystals,  c  (Fig.  178).  If  the  urine  is  allowed  to  stand  for  a  few  days, 
especially  in  a  warm  place,  or  in  a  place  where  urine  is  decomposing, 
the  reaction  becomes  ultimately  strongly  alkaline,  owing  to  the  forma- 
tion of  ammonium  carbonate  from  urea  by  the  action  of  micro-organ- 
isms {Micrococcus  urecB,  Bacterium  urecs,  and  others)  which  reach  it 
from  the  air,  and  produce  a  soluble  ferment,  in  whose  presence  the 
urea  is  split  up  with  assumption  of  water.     Thus: 


/NH2 
C^O      +  2H2O 
\NH2 

Urea. 


/O.NH4 

=  c4o 
\0.NH4. 

Ammonium  carbonate. 


This  is  a  reaction  of  considerable  interest,  for  the  reverse  reaction 
occurs  when  blood  containing  ammonium  carbonate  is  circulated 
through  the  liver,  the  ammonium  carbonate  being  converted  into  urea 
with  loss  of  water. 

tion  as  a  standard.  Fehling's  solution  is  employed  because  it  is  a  blue 
liquid  of  a  definite  depth  of  tint  already  prepared  in  every  physiological 
laboratory 


EXCRETION  BY  THE  KIDNEYS 


473 


The  substances  insoluble  in  alkaline  urine  are  thrown  down,  the 
deposit  containing  ammonio-magnesic  or  triple  phosphate,  formed  by 
the  union  of  ammonia  with  the  magnesium  phosphate  present  in  fresh 
urine,  and  precipitated  as  clear  crj^^stals  of  '  knife-rest  '  or  '  coffin-lid  ' 
shape  (Fig.  179),  along  with  amorphous  earthy  phosphates,  and  often 
acid  ammonium  urate  in  the  form  of  dark  balls  occasionally  covered 
with  spines  (Fig.  182).  Calcium  phosphate  (CaHP04)  is  another  phos- 
phate found  in  sediments  depo";ited  from  alkaline  or  faintly  acid  urine. 
It  is  usually  amorphous,  but  sometimes  in  the  form  of  long  prismatic 
crystals  arranged  in  star  fashion,  and  hence  spoken  of  as  stellar  phos- 
phate (Fig.  181).     It  is  not  pigmented. 

It  is  only  in  pathological  conditions  that  the  alkaline  fermentation 
takes  place  within  the  bladder.     The  reaction  of  the  urine  can  readily 


o 


^^ 


Fig.  179. — Triple  Phosphate.  Fig.  180. — Cystin. 


Fig.  181.— Stellar  Phos- 
phate Cr>'stals. 

be  made  alkaline  by  the  administration  of  alkalies,  alkaline  carbonates, 
or  the  salts  of  vegetable  acids  like  malic,  citric,  and  tartaric  acid,  which 
are  broken  up  in  the  body  and  form  alkaline  carbonates  with  the  alkalies 
of  the  blood  and  lymph.  It  is  not  so  easy  to  increase  the  acidity  of  the 
urine,  although  mineral  acids  do  so  up  to  a  certain  limit.  If  the  admin- 
istration of  acid  be  pushed  farther,  ammonia  is  split  off  from  the  pro- 
teins, and  is  excreted  in  the  urine  as  the  ammonium  salt  of  the  acid. 

Determination  of  the  Acidity. — A  titration  method  is  described  in 
the  Practical  Exercises  (p.  508).  In  speaking  of  the  reaction  of  blood, 
it  has  already  been  mentioned  (p.  25)  that  we  can- 
not determine  by  titration  the  true  acidity  or  alka- 
linity of  a  liquid  in  the  physico-chemical  sense — i.e., 
the  concentration  of  the  dissociated  hydrogen  and 
hydroxyl  ions  respectively.  E.g.,  when  we  titrate 
equal  quantities  of  decinormal*  acetic  acid  and  deci- 
normal  hydrochloric  acid  with  decinormal  potassium 
hydroxide,  using,  say,  phcnolphthalein  as  the  indi- 
cator, nearly  the  same  volume  of  the  potassium 
hydroxide  solution  will  be  needed  to  neutralize  each 
acid.  Yet  it  can  be  shown  by  physico-chemical 
methods  that  the  acetic  acid  in  the  strength  used  is 
only  dissociated  to  the  extent  of  a  little  more  than  i  per  cent.,  while 
about  80  per  cent,  of  the  hydrochloric  acid  is  dissociated.  The  concen- 
tration of  the  hydrogen  ions  is  therefore  eighty  times  as  great  in  the 
hydrochloric  as  in  the  acetic  acid  solution.  What  we  determine  by  the 
titration  is  not  the  true  acidity,  but  the  total  amount  of  hydrogen  which 
can  be  replaced  by  metal.  The  concentration  of  the  hydrogen  ions  in 
normal  urine  is  very  small,  on  the  average  only  about  0-003   milli- 

*  A  normal  solution  of  a  substance  contains  in  a  litre  a  number  of  grammes 
of  the  substance  equal  to  the  number  which  expresses  its  equivalent  weight 
— a  decinormal  (usually  written  ^)  solution  one-tenth  of  this  amount,  a 
centinormal  one-hundredth,  etc.  Thus,  a  normal  solution  of  potassium 
hydroxide  contains  56  grammes  o£  KOH,  and  a  decinormal  solution  5*6 
grammes  in  1,000  c.c. 


Fig.  182.  —  Ammo- 
nium Urate  (after 
Milroy). 


474  EXCRETION 

gramme  in  the  litre,  or  about  thirty  times  as  much  as  is  present  in  the 
purest  distilled  water.  Urine  departs  about  as  much  from  neutrality  in 
the  one  direction  as  blood  does  in  the  other. 

Urea,  CO(NH2)2,  is  the  form  in  which  by  far  the  greater  part  of  the 
nitrogen  is  under  ordinary  conditions  discharged  from  the  body.  Its 
amount  is  as  important  a  measure  of  protein  metabolism  as  the  quantity 
of  carbon  dioxide  given  out  by  the  lungs  is  of  the  oxidation  of  carbon- 
aceous material.  Yet  a  glance  at  the  table  on  p.  471  shows  that,  when 
the  total  protein  metabolism  is  greatly  reduced  by  diminishing  the 
protein  in  the  food,  the  relativ^e  as  well  as  the  absolute  amount  of 
nitrogen  eliminated  as  urea  suffers  a  great  diminution.  The  relative 
amount  of  the  other  nitrogenous  urinary  constituents,  especially  of 
the  kreatinin,  is  markedly  increased.  The  significance  of  this  difference 
is  alluded  to  in  speaking  of  the  kreatinin  content  of  urine,  and  will  have 
to  be  again  considered  under  Protein  Metabolisrji.  Urea  is  soluble  in 
water  and  in  alcohol,  and  crystallizes  from  its  solutions  in  the  form  of 
long  colourless  needles,  or  four-sided  prisms  with  pyramidal  ends.  It 
can  be  easily  prepared  from  urine.  Urea  can  also  be  obtained  artificially 
by  heating  its  isomer,  ammonium  cyanate  (NH4— O— CN),  to  100°  C. 
This  reaction  is  of  great  historical  interest,  as  it  forms  the  final  step 
in  Wohler's  famous  synthesis  of  urea,  the  first  example  of  a  complex 
product  of  the  activity  of  living  matter  being  formed  from  the  ordinary 
materials  of  the  laboratory.  Heated  in  watery  solution  in  a  sealed 
tube  to  180°  C,  urea  is  entirely  split  up  into  carbon  dioxide  and  am- 
monia, a  change  which  can  also  be  brought  about,  as  already  mentioned, 
by  the  action  of  micro-organisms.  Nitrous  acid,  hypochlorous  acid,  and 
salts  of  hypobromous  acid  carry  the  decomposition  still  farther,  carbon 
dioxide,  nitrogen,  and  water  being  the  products  of  their  oxidizing  action 
on  urea.  Thus:  C0.2(NH2) +3NaBrO=  3NaBr  +  2H20+ CO2+ N2. 
This  reaction  is  the  basis  of  the  hypobromite  method  of  estimating  the 
quantity  of  urea  in  urine  (Practical  Exercises,  p.  512). 

Ammonia. — The  ammonia  in  urine  is  united  with  acids  in  the  form 
of  salts.  Its  formation  from  proteins  is  determined,  as  we  shall  see 
later  on,  by  the  necessity  of  neutralizing  certain  acids  produced  in 
metabolism — e.g.,  those  derived  from  the  sulphur  and  phosphorus  of  the 
proteins,  or  acids  administered  experimentally.  According  to  some 
observers,  the  percentage  amount  of  the  total  nitrogen  in  the  urine 
in  the  form  of  ammonia  remains  the  same  whether  the  food  be  rich  or 
poor  in  protein  (Schittenhelm,  etc.),  but  others  state  that  when  the 
protein  is  reduced  there  is  a  relative  increase  in  the  ammonia-nitrogen 
(see  table  on  p.  471)  (Folin). 

Uric  acid  (C5H4N4O3)  exists  in  large  amount  in  the  urine  of  birds. 
The  excrement  of  serpents  consists  almost  entirely  of  uric  acid.  In 
both  cases  it  is  mainly  in  the  form  of  acid  ammonium  ura.te.  In  con- 
trast to  urea,  uric  acid  is  very  insoluble,  requiring  1,900  parts  of  hot 
and  15,000  parts  of  cold  water  to  dissolve  it.  In  man  and  mammals 
the  quantity  is  comparatively  small  in  health,  but  is  increased  after 
a  meal  containing  material  {e.g.,  thymus  gland)  rich  in  nucleins, 
from  the  nucleic  acid  of  which  purin  bodies  are  derived,  or  sub- 
stances containing  purin  bases  in  the  free  state — e.g.,  hypoxanthin 
in  meat.  In  mammals  the  amount  of  uric  acid  excreted  depends 
little,  if  at  all,  upon  the  quantity  of  protein  in  the  food,  but  a  great  deal 
upon  the  quantity  of  purin  bodies,  whether  free  or  combined.  When 
nitrogenous  food  is  omitted  altogether,  the  absolute  quantity  of  uric 
acid  is  diminished,  but  the  proportion  of  the  total  nitrogen  of  the  urine 
eliminated  ;  s  uric  acid  is  incrviased,  since  the  '  endogenous  '  uric  acid 
(p.  585)  still  continues  to  be  formed  and  excreted. 


EXCRETION  BY  THE  KIDNEYS 


475 


The  purin  bases  (sometimes  called  the  nuclein  bases,  the  alloxuric 
bases,  or  the  xanthin  bases)  arc  a  group  of  substances  allied  to  uric 
acid,  and  including,  besides  xanthin  itself,  hypoxanthin,  guanin,  adenin, 
and  other  bodies.  They  exist  in  very  small  amount  in  urine,  but,  like 
uric  acid,  are  increased  in  amount  by  the  ingestion  of  nuclein-contain- 
ing  substances.  The  greater  part  of  the  purin  bases  produced  in  the 
body  is  transformed  into  uric  acid  ;  it  is  only  the  untransformed  residue 
which  appears  in  the  urine.  An  interesting  fraction  of  the  purin  bases 
in  the  urine  which  is  not  related  to  the  nuclein  metabolism  is  composed 
of  the  so-called  hctcroxanthin,  derived  from  caffeine  in  the  coffee  and 
tea,  /-methylxanthin,  deri\Td  from  theobromine  in  the  cocoa,  and  para- 
xanthin,  derived  from  theophyllin  in  the  tea,  consumed  as  beverages. 

Hippuric  acid  (C9H9NO3)  occurs  in  considerable  quantity  in  the  urine 
of  herbivora  (Practical  Exercises,  p.  516);  in  the  urine  of  carnivora  and 
of  man  only  in  traces;  in  that  of  birds  not  at  all.  Its  amount  is  much 
more  dependent  on  the  presence  of  particular  substances  in  the  food 
than  that  of  the  other  organic  constituents  of  urine.  Anything  which 
contains  benzoic  acid,  or  substances  which  can  be  readily  changed  into 
it  (such  as  cinnamic  and  quinic 
acids),  causes  an  increase  of  the 
hippuric  acid  in  urine.  In  fact, 
one  of  the  best  ways  of  obtaining 
the  latter  is  from  the  urine  of  a 
person  to  whom  benzoic  acid  is 
given  by  the  mouth;  the  sweat 


Fig.  183. — Kreatin. 


Fig.  184. — Kreatinin -Zinc-Chloride. 


may  also  in  this  case  contain  a  trace  of  hippuric  acid.  Chemically  it 
is  a  conjugated  acid  formed  by  the  union  of  benzoic  acid  and  glycin. 

Amino-Acids. — The  only  amino-acid  hitherto  detected  with  certainty 
in  normal  urine  is  glycin. 

Oxalic  acid  is  always  present,  although  in  very  small  amount.  Some 
of  it  comes  from  the  oxalates  of  the  food,  but  a  portion  of  it  arises  in 
the  metabolism  of  the  tissues,  probably  from  the  decomposition  of  uric 
acid.  It  is  known  that  outside  of  the  body  uric  acid  may  be  made  to  yield 
oxalic  acid .  Ca  cium  oxalate  crystals  are  often  seen  in  urinary  sediments. 

Kreatinin  (C4H7N3O). —  Kreatinin  is  the  anhydride  of  kreatin 
(Fig.  183).  Its  formula  differs  from  that  of  kreatin  only  in  possessing 
the  elements  of  one  molecule  of  water  l^ss ;  and  kreatinin  can  be 
obtained  by  boiling  kreatin  with  dilute  sulphuric  acid.  From  its 
alcoholic  solution  it  crystallizes  in  colourless  prisms.  Kreatinin  forms 
crystalline  compounds  with  various  acids  and  salts.  One  of  tlu"  best 
known  of  these  is  krcatinin-zinc-chloride,  formed  on  the  addition  of 
zmc  cliloridc  to  an  alcoholic  or  watery  solution  of  kreatinin,  often  in 
the  shape  of  beautiful  thick-set  rosettes  of  needles  (Fig.  184).     A  per- 


476  EXCRETION 

tion  of  the  urinary  kreatinin  is  derived  from  the  kreatin  of  the  meat 
taken  as  food.  But  this  is  not  its  only  source,  for  on  a  meat-free  diet 
and  in  starvation  kreatinin  is  still  excreted.  The  absolute  quantity  in 
the  urine  on  a  meat-free  diet  is  constant  for  one  and  the  same  individual, 
although  different  in  different  persons,  and  independent  of  the  total 
amount  of  nitrogen  eliminated.  Hence  on  a  diet  poor  in  protein  the 
percentage  of  the  total  nitrogen  excreted  as  kreatinin  is  much  greater 
than  on  a  protein-rich  diet,  as  sIiomti  in  the  table  on  p.  471 .  So  constant 
is  the  quantity  that  a  determination  of  the  kreatinin  may  be  used  as  a 
check  upon  the  complete  collection  of  the  urine. 

Carbo-hydrates  are  normally  present  in  human  urine,  but  only  in 
very^  small  amounts.  Three  are  known  with  certainty — dextrose, 
isomaltose,  and  the  so-called  animal  gum  or  urine  dextrin.  Glycuronic 
acid  (C6H10O7),  a  body  which  can  be  derived  from  dextrose,  is  con- 
stantly present  in  small  amount  as  a  conjugated  acid,  paired  with 
phenol  or  indoxyl.  It  gives  Fehling's  test,  and  thus  may  easily  be 
mistaken  for  sugar.  Glycuronic  acid  becomes  coupled  very  easily  with 
a  large  variety  of  substances,  including  many  drugs,  and  care  must  be 
taken  after  the  administration  of  camphor,  chloral  hydrate,  chloro- 
form, nitrobenzol,  etc.,  not  to  confound  the  largely  increased  excretion 
of  conjugate  glycuronates  in  the  urine  with  glycosuria.  The  yeast  test 
will  turn  out  negative  if  the  reduction  is  due  to  glycuronic  acid,  and 
the  polarimeter  will  show  rotation  to  the  right  if  it  is  due  to  dextrose - 
The  total  quantity  of  carbo-hydrates,  including  glycuronic  acid, 
excreted  in  the  urine  of  the  twenty-four  hours  has  been  estimated  at 
2  to  3  grammes.  The  quantity  of  dextrose  in  normal  human  urine  is 
about  0-02  per  cent.,  or  about  one-fifth  of  the  proportion  in  blood. 

Proteins,  mainly  serum-albumin,  are  also  found  in  normal  urine  in 
minute  quantities,  on  the  average  about  0'0036  per  cent.  (Momer). 

Pigments  of  Urine. — The  pigments  of  urine  have  not  hitherto  been 
exhaustively  studied ;  but  we  already  know  that  normal  urine  contains 
several,  and  pathological  urines  probably  additional,  pigmentary  sub- 
stances. The  best-known  pigments  in  normal  urine  are  urochrome, 
the  yellow  substance  which  gives  the  liquid  its  ordinary  colour; 
uroerythrin,  the  pink  pigment  which  often  colours  the  deposits  of  urates 
that  separate  even  from  healthy  urine;  and  urobilin,  which,  as  has  been 
already  stated,  is  identical  with  the  faecal  pigment  stercobilin,  and  occurs 
not  only  in  many  febrile  conditions,  but  also  in  cases  with  no  fever,  such 
as  functional  derangements  of  the  liver,  dyspepsia,  chronic  bronchitis, 
and  valvular  diseases  of  the  heart.  The  urobilin  of  urine  represents, 
mainly  at  least,  the  portion  of  the  stercobilin  which  is  not  excreted  with 
the  faeces,  but  absorbed  from  the  intestine  into  the  blood.  The  urobilin 
in  normal  urine  only  exists  in  small  amount  in  the  fully-formed  con- 
dition, most  of  it  being  present  as  a  chromogen  or  mother-substance 
(urobilinogen),  which  by  oxidation,  as  on  standing  exposed  to  the  air, 
is  converted  into  urobilin.  On  the  addition  of  ammonia  and  zinc 
chloride  to  a  solution  of  urobilin  a  beautiful  green  fluorescence  is 
obtained,  and  the  solution  now  shows  an  absorption  band  between 
b  and  F.  Urobilin  and  urochrome  are  related  substances,  but  the  exact 
nature  of  the  relation  has  not  been  settled.  There  is  some  evidence 
that  a  portion  of  the  urobilin  of  urine  is  not  derived  from  the  intestine, 
but  manufactured  probably  in  the  liver.  In  hunger  urobilin  is  still 
excreted  in  the  urine,  although  in  greatly  reduced  amount.  During 
menstruation  it  is  markedly  increased,  both  in  fasting  and  in  normally 
fed  individuals.  Urorosein  is  a  red  pigment  which  is  produced  from 
its  chromogen  by  the  action  of  mineral  acids — e.g.,  strong  hydrochloric 
acid — in  the  presence  of  an  oxidizing  agent,  especially  nitrites. 


EXCRETION  BY  THE  KIDNEYS 


477 


The  pigments  of  the  blood  and  bile  and  some  of  their  derivatives  arc 
of  common  occurrence  in  the  urine  in  disease.  Hcematoporphyrin  has 
not  only  been  found  in  some  pathological  conditions,  but  is  constantly 
present  in  minute  traces  in  normal  urine.  Certain  drugs — e.g.,  sulphonal 
— cause  an  increase  in  its  amount.  In  paroxysmal  ha^moglobinuria, 
methcenioglobin ,  mixed  with  some  oxy haemoglobin,  is  found  in  the  urine  in 
large  amount;  and  it  is  worthy  of  note  that  it  is  not  formed  in  the  urine 
after  secretion,  but  is  already  present  as  such  when  it  reaches  the  bladder. 

In  the  rare  condition  termed  alkaptonuria,  a  body,  alkapton,  now 
known  to  be  identical  with  homogentisinic  acid,  CfiH3.(OH)2CH2.COOH, 
a  dioxyphenylacetic  acid,  is  present.  The  urine  becomes  dark  brown 
on  tl;e  addition  of  an  alkali,  or  simply  on  exposure  to  air.  It  gives 
Fehling's  test  for  sugar.  The  substance  has  relations  to  the  aromatic 
amino-acids  tyrosin  and  phenyl-alanin,  and  when  either  of  these  is 
given  to  a  person  suffering  from  alkaptonuria,  the  amount  of  alkapton 
excreted  is  increased.  We  may  suppose,  therefore,  that  in  this  con- 
dition the  normal  decomposition  of  these  products  of  proteolysis  is 
interfered  with. 

Ferments.^The  urine  contains  traces  of  proteolytic  and  amylol>i:ic 
ferments  (Fig.  183).  These  may  be  easily  separated  from  it  by  putting 
a  httle  fibrin,  which  has  the  power  of  fixing  (adsorbing)  enzymes,  into 
the  urine. 

Of  the  inorganic  constituents  of  urine  the  most  important  and 
most  easily  estimated  are  the  clilorine,  phosphoric  acid,  and  sul- 
phuric acid. 


Fig.  185. — Pepsin  in  Urine.     Diastatic  Ferment  in  Urine. 
At  Different  Times  of  the  Day  (Hoffmann). 

Chlorine.-^Much  the  greater  part  of  the  chlorine  is  united  with 
sodium,  a  smaller  amount  with  potassium.  The  chlorides  of  the  urine 
are  undoubtedly  to  a  great  extent  derived  directly  from  the  chlorides 
of  the  food,  and  have  not  the  same  metabolic  significance  as  the  organic, 
and  even  as  some  of  the  other  inorganic  constituents.  But  it  is  note- 
worthy that  in  certain  diseased  conditions  the  chlorine  may  disappear 
entirely  from  the  urine,  or  be  greatly  diminished — e.g.,  in  pneumonia, 
and  in  general  in  cases  in  which  much  material  tends  to  pass  out  from 
the  blood  in  the  form  of  effusions  (p.  508). 

Phosphoric  Acid.— The  phosphoric  acid  of  the  urine  is  chiefly  derived 
from  the  phosphates  of  the  food,  but  must  partly  come  from  the  waste 
products  of  tissues  rich  in  phosphorus-containing  substances,  such  as 
lecithin  and  nuck  in.  The  phosphoric  acid  is  united  partly  with  alkalies, 
especially  as  acid  sodium  phosphate,  and  j)artly  with  earthy  bases,  as 
phosphates  of  calcium  and  magnesium.  The  earthy  phosphates  are 
precipitated  by  the  addition  of  an  alkali  to  urine,  or  in  the  alkaline 


478  EXCRETION 

fermentation.  In  some  pathological  urines  they  come  down  when  the 
carbon  dioxide  is  driven  off  by  heating;  a  precipitate  of  this  sort  differs 
from  heat-coagulated  albumin  in  being  readily  soluble  in  acids  (Practical 
Exercises,  p.  516).  A  small  amount  of  phosphorus  may  appear  in  the 
urine  in  a  less  oxidized  form  than  phosphoric  acid. 

Sulphuric  Acid. — This  is  only  to  a  slight  extent  derived  from  ready- 
formed  sulphates  in  the  food.  The  greater  part  of  it  is  formed  by 
oxidation  of  the  sulphur  of  proteins.  About  nine-tenths  of  the  sulphur 
in  normal  urine  is  present  as  inorganic  sulphates,  mainly  those  of 
potassium  and  sodium.  Of  the  other  tenth,  a  portion  is  represented 
by  ethereal  sulphates,  and  the  ren:iainder  by  the  so-called  '  neutral  ' 
sulphur,  including  the  sulphur  associated  with  the  pigment  urochrome. 
A  small  amount  of  sulphur  occurs  in  less  oxidized  forms  than  sul- 
phates in  such  compounds  as  the  sulphocyanide,  which  is  probably, 
in  part  but  not  entirely,  derived  from  that  of  the  saliva,  and  ethyl 
sulphide,  a  substance  with  a  penetrating  odour,  which  appears  to  be  a 
constant  constituent  of  dog's  urine  (Abel). 

Thiosulphuric  acid  (H2S2O3)  occurs  almost  constantly  in  cat's  urine, 
often  in  dog's.     It  is  not  free,  but  combined  with  bases. 

The  ethereal  sulphates  are  compounds  in  which  the  sulphuric  acid  is 
united  with  aromatic  bodies  (indol,  phenol,  etc.).  Such  are  potassium- 
phenyl-sulphate  (CgH5KS04),  potassium-kresyl-sulphate  (C7H7KSO4), 
potassium-indoxyl-sulphate  (C8HeNKS04),  potas^ium-skatoxyl-sulphate 
(C9H8NKSO4),  and  two  double  sulphates  of  potassium  and  pyrocatechin. 
The  formation  of  potassium  indoyxl  sulphate  may  be  thus  represented : 

/r"l-T  Cl-T 
Indol,  C(jH4C    ^tt'        on  absorption  from  the  intestine  is  changed  into 

indoxyl,    C6H4<(' -kt'tt     "       '    which    +   ^*^2\  oK    (Potassium   hydrogen 

sulphate)   yields    S02\' qt^    ^       (potassium   indoxyl    sulphate)  4- HgO. 

The  '  pairing  '  of  these  aromatic  bodies  with  sulphuric  acid  renders 
them  innocuous  to  the  organism.  Most  of  the  compounds  are  present 
in  greater  amount  in  the  urine  of  the  horse  than  in  the  normal  urine  of 
man.  But  in  disease  the  quantity  of  indican  in  the  latter  may  be  much 
increased ;  and  to  a  certain  extent  it  must  be  looked  upon  as  an  index 
of  the  intensity  of  putrefactive  processes  in  the  intestine  and  of  absorp- 
tion from  it.  Munk  made  the  observation  that  in  the  urine  of  a  starving 
dog  the  phenol-forming  substances  are  absent,  while  in  the  urine  of  a 
starving  man  they  are  present  in  abnormally  large  amount.  The 
indigo-forming  substances  (indican),  on  the  other  hand,  are  in  hunger 
excreted  in  considerable  quantity  by  the  dog,  and  not  at  all  by  man 
(Practical  Exercises,  p.  510).  According  to  Folin,  the  indoxyl  potassium 
sulphate  or  indican  of  the  urine  is  not  to  any  appreciable  extent  related 
to  protein  metabolism,  but  for  the  most  part  to  the  putrefaction  of 
protein  in  the  intestine.  The  indoxyl-potassium  sulphate  taken  by  itself 
may  therefore  afford  a  rough  index  of  the  intensity  of  the  intestinal 
putrefactive  processes.  On  the  other  hand,  the  total  ethereal  sulphuric 
acid  cannot  be  taken  as  an  index  of  the  extent  of  the  putrefaction,  for, 
although  absolutely  diminished,  it  is  increased  relatively  to  the  total 
excretion  of  sulphur  on  a  diet  poor  in  protein,  or  even  protein-free 
(see  tables  on  p.  471). 

Phenol  and  kresol  can  easily  be  obtained  from  horse's  urine  by 
mixing  it  with  strong  hydrochloric  acid  and  distiUing.  TheS'>  aromatic 
bodies  pass  over  in  the  distillate.  Pyrocatechin  remains  behind,  and 
can  be  extracted  by  ether.  It  gives  a  green  colour  with  ferric  chloride, 
which  becomes  violet  on  the  addition  of  sodium  carbonate. 


EXCRETION  BY  THE  KIDNEYS 


479 


The  sulphur  of  the  inorganic  sulphates  is  the  fraction  of  the  total 
sulphur  which  fluctuates  in  proportion  to  the  total  protein  metabolism. 
In  this  regard  it  follows  the  variations  in  the  urea.  It  represents 
'exogenous'  metabolism.  The  neutral  sulphur  occupies  a  position 
analogous  to  that  of  the  kreatinin:  the  smaller  the  amount  of  protein 
in  the  food,  and  the  smaller  therefore  the  total  protein  decomposed,  the 
larger  is  the  fraction  which  the  neutral  sulphur  forms  of  the  total 
sulphur.  The  neutral  sulphur  accordingly  represents  endogenous 
metabolism.  The  ethereal  sulphur  takes  an  intermediate  position  in 
this  regard,  but  upon  the  whole  it  also  becomes  a  more  prominent 
fraction  of  the  total  sulphur  when  the  food  contains  little  or  no  protein. 
The  ethereal  sulphates  are  therefore  not  entirely  derived  from  the 
putrefaction  of  protein. 

Carbonates  of  sodium,  ammonium,  calcium,  and  magnesium  occur 
in  alkaline  urine.  Their  source  is  the  carbonates  and  the  vegetable 
organic  acids  of  the  food.  In  acid  urine  a  certain  amount  of  carbon 
dioxide  is  present,  although  not  firmly  united  with  bases,  so  that  m)st 
of  it  can  be  pumped  out. 

Physico-Chemical  Analysis  of  Urine. — Tho  freezing-point  of  urine  is 
often  determined  to  obtain  a  measure  of  the  molecular  concentration, 
which  with  the  total  quantity  of  urine  secreted  in  a  given  time  is  an 
index  of  the  work  of  the  kidney.  The  greater  the  volume  of  urine 
secreted  per  unit  of  time,  and  the  greater  the  number  of  molecules 
dissolved  in  unit  volume  of  it,  the  greater  is  the  work  of  the  secretory 
apparatus  in  separating  it  from  the  blood  (p.  497).  Normally,  A  has  a 
higher  value  for  urine  than  for  blood — i.e.,  the  molecular  concentration 
of  the  urine  is  higher  than  that  of  the  serum.  But  when  large  draughts 
of  water  are  taken  A  may  be  lower  for  urine  than  for  blood,  and  in 
general  it  varies  within  far  wider  limits  (from  0'ii5°  to  2-546°  C, 
according  to  Koppe).  The  following  table  from  Kovesi  and  Roth- 
Schulz  shows  the  changes  in  A  under  the  influence  of  water: 


Time. 

Urine  in  C.C. 

A 

10  to  2 

240 

I -So 

2  to  6 

255 

172 

6  to  10 

161 

1-93 

10  to  2 

131 

2-l8 

2  to  6 

160 

2-23 

6  to  10 

120 

I-9I 

II  to  12 

1-8  litres  '  Salvator  '  water  taken 

— 

12  to  12.30 

500 

0'12 

12.30  to  I 

444 

O-II 

I  to  1.30 

442 

O'lO 

1.30  to  2 

46 

078 

2  to  2.30 

45 

I -30 

1 

If  the  electrical  conductivity  is  determined,  we  obtain  an  approxi- 
mate measure  of  the  number  of  dissociated  ions  in  unit  volume,  mainly 
the  inorganic  salts.  Deducting  this  from  the  total  number  of  molecules 
per  unit  volume  (measured  by  A),  we  arrive  at  the  concentration  of 
the  urine  in  non-dissociated  molecules,  mainly  urea  and  other  organic 
constituents.  Precision  is  added  to  such  calculations  by  estimating 
also  in  the  ordinary  way  (by  titration,  e.g.)  one  or  more  of  the  inorganic 


480 


EXCRETION 


constituents,  especially  the  chlorine,  since  sodium  chloride  is  quanti- 
tatively the  most  important  of  the  salts.  Various  formulae  have  been 
deduced  from  such  determinations  connecting  the  freezing-point  and 

conductivity  with  other  physical  constants  of  the  urine.     E.g., = 

K— 75,  where  s  is  the  specific  gravity  and  K  a  constant  with  the  value 
75.  The  quotient  ,..  p.,  representing  the  ratio  of  the  total  concen- 
tration to  the  sodium  chloride  concentration,  varies  within  relatively 
narrow  limits  in  health,  according  to  Koranyi,  the  diet  exercising  no 
influence    upon    it    whatever.     Thus,    in    a    large    number   of    healthy 

individuals  ,,   „,  fluctuated  only  between  1-2^  and  I'Cq,  while  A  varied 
NaCl  ■' 

from  I -26°  to  2 •35°.  and  the  percentage  of  sodium  chloride  from  0-85 

to  I '54.     This  is  illustrated  in  the  table: 


( 

Urine  in  C.C.  in 

A 

Percentage  of 

1 

A 

Twenty-four  Hours. 

NaCl. 

NaCr 

1-365 

1-43° 

I -08 

1-32 

1.745 

I -60° 

1-24 

1*29 

1,680 

1-68= 

1-28 

1-31 

I.OI5 

1-84° 

1-15 

I -60 

865 

i-8i° 

1-26 

1-44 

1,360 

1-62° 

I -09 

1-49 

840 

2-26° 

I -50 

I-5I 

1,600 

1-46° 

I-I4 

1-28 

2,080 

1-33° 

0-85 

1-68 

The  Urine  in  Disease. — Although,  strictly  speaking,  a  truly  patho- 
logical urine  has  no  place  in  physiology,  the  line  which  separates  the 
urine  of  health  from  that  of  disease  is  often  narrow,  sometimes  invisible ; 
while  the  study  of  abnormal  constituents  is  not  only  of  great  importance 
in  practical  medicine,  but  throws  light  upon  the  physiological  processes 
taking  place  in  the  kidney,  and  upon  the  general  problems  of  metabolism. 
Even  in  health  the  quantity  of  the  urine,  its  specific  gravity,  its  "acidity, 
may  vary  within  wide  limits.  A  hot  day  may  increase  the  secretion 
of  sweat,  and  correspondingly  diminish  the  secretion  of  urine,  and  the 
deficiency  of  water  may  lead  to  a  deposit  of  brick-red  urates.  A  meal 
rich  in  fruit  or  vegetables  may  render  the  urine  alkaline,  and  its  alkalinity 
may  determine  a  precipitate  of  earthy  phosphates.  But  neither  the 
scanty  acid  urine  with  its  sediment  of  urates,  nor  the  alkaline  urine 
with  its  sediment  of  phosphates,  comes  into  the  category  of  pathological 
urines;  the  deviation  from  the  normal  does  not  amount  to  disease. 
The  maximum  deviation  from  the  line  of  health  is  the  total  suppression 
of  the  urine.  If  this  lasts  long,  a  train  of  symptoms,  of  which  con- 
vulsions may  be  one  of  the  most  prominent,  and  which  are  grouped 
under  the  name  of  uraemia,  appears.  At  length  the  patient  becomes 
comatose,  and  death  closes  the  scene.  Suppression  of  urine  may  be 
the  consequence  of  many  pathological  conditions,  but  there  is  one  case 
on  record  in  the  human  subject  which,  in  effect,  though  not  in  intention, 
belongs  to  experimental  physiology.  A  surgeon  diagnosed  a  floating 
kidney  in  a  woman.  With  a  na.tural  impatience  of  loose  odds  and 
ends  of  this  sort,  he  offered  to  remove  it,  and  in  an  evil  hour  the  patient 
consented.     The  surgeon,  a  perfectly  sldlful  man,  who  acted  for  the 


EXCRETION  BY  THE  KIDNEYS  4S1 

best,  and  to  whom  no  blame  whatever  attached,  carried  the  kidney  to 
a  well-known  pathologist  for  examination.  The  latter,  to  the  horror 
of  the  operator,  suggested,  from  the  appearance  of  the  organ,  that  it 
was  the  only  kidney  the  woman  possessed.  This  turned  out  to  be  the 
fact.  Not  a  drop  of  urine  was  passed.  Apart  from  this  ominous 
symptom,  all  went  well  for  seven  or  eight  days;  but  then  ur^emic 
troubles  came  on,  and  the  patient  died  on  the  eleventh  or  thirteenth 
day  after  the  operation.  The  necropsy  showed  that  her  only  kidney 
had  been  taken  away. 

In  disease  the  urine  may  contain  abnormal  constituents,  or  ordinary 
constituents  in  abnormal  amounts.  Of  the  normal  constituents  which 
may  be  altered  in  quantity,  the  most  important  are  the  water,  the  inor- 
ganic salts,  the  urea,  the  uric  acid,  and  the  aromatic  substances. 

Water. — A  marked  and  persistent  diminution  in  the  quantity  of 
urine — that  is  to  say,  practically  in  the  water,  with  or  without  an 
increase  in  the  specific  gravity — is  suggestive  of  disorganization  of  the 
renal  epithelium.  In  some  infective  diseases  the  kidney  is  liable  to 
be  secondarily  involved,  its  secreting  cells  being  perhaps  crippled  in  the 
attempt  to  eliminate  the  bacterial  poisons.  In  the  form  of  paren- 
chymatous or  tubal  nephritis  wliich  so  frequently  complicates  scarlet 
fever,  the  quantity  of  urine  has  in  some  cases  fallen  to  50  or  60  c.c.  in 
the  twenty -four  hours. 

In  chronic  interstitial  nephritis  ('  granular  kidney  '),  on  the  other 
hand,  where  the  structural  changes  in  the  tubules  are,  for  a  long  time 
at  least,  comparatively  circumscribed,  the  quantity  of  urine  is  often 
increased  and  of  low  specific  gravity.  In  these  cases  the  increase  in 
the  blood-pressure,  associated  with  hypertrophy  of  the  heart,  may  be 
a  factor  in  the  exaggerated  renal  secretion.  In  diabetes  mellitus  the 
quantity  of  urine  is  greatly  increased,  perhaps  in  some  cases  because 
more  urea  is  excreted  than  normal,  and  urea  acts  as  a  diuretic,  perhaps 
also  because  the  elimination  of  sugar  draws  with  it  an  increased  excretion 
of  water  to  hold  it  in  solution.  Although  a  specific  gravity  as  low  as 
1002  has  been  seen  in  healthy  persons  (after  copious  potations),  the 
persistence  of  a  density  below  loio  should  suggest  hydruria.  Watson 
mentions  the  case  of  a  boy  with  diabetes  insipidus,  who  voided  in 
twenty-four  hours  9  or  10  pints  (5  to  6  litres)  of  urine  with  a  specific 
gravity  of  1002.  On  the  other  hand,  while  the  specific  gravity  has  been 
occasionally  observed  to  mount  in  health  to  at  least  1036,  its  persistence 
at  1025  or  1030  or  anything  above  this,  especially  if  the  urine  is  pale 
and  apparently  dilute,  should  suggest  diabetes  mellitus. 

Inorganic  Salts. — The  changes  in  the  quantity  of  the  inorganic  con- 
stituents of  the  urine  in  disease  are  not,  in  the  present  state  of  our 
knowledge,  of  as  much  importance  as  the  changes  in  the  organic  con- 
stituents. The  chlorides  are  diminished  in  most  acute  febrile  diseases 
and  may  even  totally  disappear  from  the  urine,  and  their  reappearance 
after  the  crisis  is,  so  far  as  it  goes,  a  favourable  symptom.  In  most 
cases  in  which  the  quantity  of  the  urine  is  markedly  lessened,  all  the 
inorganic  substances  are  diminished  in  amount. 

Urea. — The  quantity  of  urea  is,  as  a  rule,  increased  in  fever,  either 
absolutely  or  in  proportion  to  the  amount  of  nitrogen  in  the  food.  In 
the  interstitial  varieties  of  kidney  disease  the  urea  is  usually  not 
diminished,  but  when  the  stress  of  the  change  falls  on  the  tubules 
(parenchymatous  nephritis),  it  is  distinctly  decreased — it  may  be  even 
to  one-twentieth  of  the  normal. 

Uric  acid  is  diminished  in  the  urine  in  gout  (perhaps  to  one-ninth  of 
the  normal),  not  only  during  the  paroxysms,  but  in  the  intervals.  It 
accumulates  in  the  blood  and  tissues,  and,  as  sodium  urate,  may  form 

31 


482  EXCRETION 

concretions  in  the  joints,  the  cartilage  of  the  ear,  and  other  situations, 
Watson  relates  the  case  of  a  gentleman  who  used  to  avail  himself  of  his 
resources  in  this  respect  by  scoring  the  points  at  cards  on  the  table  with 
his  chalky  knuckles.  In  leukaemia  the  quantity  of  uric  acid  and  purin 
bases  in  the  urine  is  greatly  increased,  not  only  absolutely,  but  also  in 
proportion  to  the  urea.  As  much  as  4J  grammes  of  free  uric  acid,  in 
addition  to  about  i\  grammes  of  ammonium  urate,  has  been  fovmd  in  a 
urinary  sediment  in  a  case  of  leukaemia. 

The  aromatic  bodies,  of  which  indoxyl  may  be  taken  as  the  type, 
are  increased  when  the  conditions  of  disease  favour  the  growth  of 
bacteria  in  the  intestine — e.g.,  in  cholera,  acute  peritonitis,  and  carci- 
noma of  the  stomach.  A  marked  increase  in  the  amount  of  the  indican 
in  the  urine  may,  as  far  as  it  goes,  be  taken  as  an  indication  that  the 
bacteria  are  gaining  the  upper  hand  in  the  intestinal  tract;  a  marked 
diminution  is  usually  a  sign  that  the  battle  has  begun  to  turn  in  favour 
of  the  organism  (Practical  Exercises,  p.  510).  Tryptophane,  a  sub- 
stance which  we  have  already  recognized  among  the  products  of  the 
tryptic  digestion  of  proteins,  has  been  shown  to  be  a  precursor  of  indol, 
which  is  formed  from  it  under  the  influence  of  bacteria.  When  trypto- 
phane is  injected  into  the  caecum  of  rabbits,  the  indican  in  the  urine 
is  markedly  increased.  Putrefactive  processes  in  other  parts  of  the 
body  than  the  intestine  may  also  increase  the  indican  in  the  urine — 
e.g.,  a  collection  of  putrid  pus  in  the  pleural  cavity. 

Abnormal  Substances  in  Urine. — Sugar,  proteins,  the  pigments  of  bile 
and  blood,  or  their  derivatives,  are  the  most  important  abnormal  sub- 
stances found  in  solution  in  the  urine.  Normal  urine,  as  has  been 
stated,  contains  a  trace  of  dextrose,  but  so  little  that  it  cannot  be 
detected  by  ordinary  tests,  and  for  practical  purposes  it  may  be  con- 
sidered absent.  Dextrose  is  the  sugar  found  in  the  urine  in  diabetes. 
In  the  urine  of  nursing  mothers  lactose  may  be  present.  Pentoses, 
sugars  with  five  carbon  atoms  in  the  molecule  (instead  of  six,  as  in  the 
hexoses,  of  which  group  dextrose  is  a  member),  may  also  occasionally 
occur  in  urine.  Pentoses  give  the  ordinary  reduction  tests  for  sugar, 
and  yield  osazones,  but  do  not  ferment  with  yeast.  Various  plants 
contain  pentoses,  and  when  these  are  eaten  the  pentoses  are  excreted 
in  the  urine,  but  in  cases  of  true  pentosuria  they  originate  in  the  body, 
possibly  from  nucleo-proteins.  The  condition  has  not  the  same  sinister 
significance  as  diabetes.  Specific  toxic  substances  produced  by  bac- 
terial action  have  been  demonstrated  in  the  urine  in  certain  diseases. 
Red  blood-corpuscles  and  leucocytes  (pus  corpuscles,  white  blood- 
corpuscles,  mucous  corpuscles)  are  the  chief  organized  deposits;  but 
spermatozoa  may  occasionally  be  found,  as  well  as  pathogenic  bacteria — 
e.g.,  the  typhoid  bacillus;  and  in  disease  of  the  kidney  casts  of  the  renal 
tubules  are  not  uncommon.  These  tube-casts  may  be  composed  chiefly 
of  red  blood -corpuscles,  or  of  leucocytes,  or  of  the  epithelium  of  the 
tubules,  sometimes  fattily  degenerated,  or  of  structureless  protein, 
Dr  of  amyloid  substance.  Abnormal  crystalline  substances,  such  as 
the  amino-acids,  leucin  (Fig.  186),  tyrosin  (Fig.  187),  and  cystin 
(Fig.  180),  may  be  on  rare  occasions  found  in  urinary  sediments;  but 
generally  the  unorganized  deposits  of  pathological  urine  consist  of 
bodies  actually  contained  in,  or  obtainable  from,  the  normal  secretion, 
but  present  in  excess,  either  absolutely,  or  relatively  to  the  solvent 
power  of  the  urine.  Cystin  is  of  interest  because  of  its  relations  to  the 
sulphur  of  the  protein  molecule  (p.  354).  It  is  not  found  in  the  normal 
organism.  It  very  occasionally  forms  calculi  in  the  bladder.  There 
are  individuals  who  constantly  pass  as  much  as  one -fourth  of  all  the 
sulphur  in  the  form  of  cystin,  without  any  other  symptoms. 


EXCRETION  BY  THE  KIDNEYS  483 

Various  amino-acids  are  present  in  solution  in  the  urine  in  many 
pathological  conditions.  Of  these  the  least  soluble  are  leucin  and 
tyrosin,  and  this  is  the  reason  why  they  are  most  easily  detected.  A 
general  reaction  for  amino-acids  is  their  precipitation  as  sparingly 
soluble  compounds  (/^-naphthalinsulphoncs)  by  /3-naphthalinsulpho- 
chloride  in  the  presence  of  an  alkali  (sodium  hydroxide).  In  acute 
yellow  atrophy  of  the  liver  leucin  and  tyrosin  have  been  found  in  large 
amounts  in  the  liver  itself,  as  well  as  in  the  urine.  In  phosphorus 
poisoning  these  amino-acids,  as  well  as  glycocoll,  have  been  detected  in 
the  urine,  and  there  is  no  doubt  that  other  amino-acids,  arising  from 
the  decomposition  of  proteins,  are  also  present  in  such  conditions. 

Sugar. — In  diabetes  mcllitus,  although  the  quantity  of  urine  is  usually 
much  increased,  its  specific  gravity  is  above  the  normal;  and  this  is  due 
chiefly  to  the  presence  of  sugar  (dextrose),  which  generally  amounts 
to  I  to  5  per  cent.,  but  may  in  extreme  cases  reach  10  or  even  15  per 
cent.,  more  than  half  a  kilogramme  being  sometimes  given  off  in  twenty- 
four  hours. 

The  name  of  the  tests  for  dextrose  is  legion.  They  are  mostly 
founded  on  its  reducing  action  in  alkaline  solution.  Hydrated  oxide  of 
bismuth  (Boettcher),  salts  of  gold,  platinum  and  silver,  indigo  (Mulder), 
and  a  host  of  other  substances,  are  reduced  by  dextrose,  and  may 
be  used  to  show  its  presence.     The  reduction  of  cupric  salts  (Trommer), 


Fig.   186. — Leucin  Crystals.  Fig.  187. — Tyrosin  Crystals. 

fermentation  by  yeast,  and  the  formation  of  crystals  of  phenyl-gluco- 
sazone  are  the  best  established  tests.     (See  Practical  Exercises,  p.  517.) 

Proteins. — Serum-albumin  and  serum-globulin  are  the  proteins  most 
commonly  found  in  pathological  urine.  Both  are  coagulated  by  heating 
the  urine,  slightly  acidulated  if  it  is  not  already  acid,  or  by  the  addition 
of  strong  nitric  acid  in  the  cold.  Proteoses  (albumoses)  are  also  occa- 
sionally present,  e.g.,  in  the  disease  called  '  osteomalacia  '  and  in  con- 
ditions associated  with  the  formation  and  especially  with  the  decom- 
position of  pus.  They  may  be  recognized  by  the  tests  given  in  the 
Practical  Exercises  (p.  517).  It  is  doubtful  whether  the  presence  of 
true  peptone  has  as  yet  been  satisfactorily  made  out. 

The  presence  of  bile-salts  may  be  shown  by  Hay's  test  or  Petten- 
kofer's  test  (p.  456). 

The  pigments  of  blood  and  bile  may  be  detected  by  the  characters 
described  in  treating  of  these  substances;  the  spectrum  of  oxyhaemo- 
globin,  or  methajmoglobin,  or  any  of  the  other^dcrivatives  of  haemoglobin, 
with  the  formation  of  ha^min  crystals,  would  afford  proof  of  the  presence 
of  the  former,  and  Gmelin's  test  of  the  latter.  The  red  blood-corpuscles, 
seen  with  the  microscope,  are  the  most  decisive  evidence  of  the  presence  of 
blood,  as  leucoc^-tes  in  abundance  are  of  the  presence  of  pus.  It  should 
be  remembered  that  pus  in  the  urine  of  women  has  sometimes  no  signifi- 
cance except  as  showing  that  there  has  been  an  admixture  of  leucorrheal 
discharge  from  the  vagina.     (See  Practical  Exercises,  pp.  74,  5^3-) 


484  EXCRETION 


Section  II. — The  Secretion  of  the  Urine. 

We  have  now  to  consider  the  mechanism  by  which  the  urine  is 
formed  in  the  kidney  from  the  materials  brought  to  it  by  the  blood. 
And  here  the  same  questions  arise  as  have  already  been  discussed 
in  the  case  of  the  salivary  and  other  digestive  glands:  (i)  Are  the 
urinary  constituents,  or  any  of  them,  present  as  such  in  the  blood  ? 
(2)  If  they  do  exist  in  the  blood,  can  they  be  shown  to  be  separated 
from  it  by  processes  mainly  physical  or  mainly  '  vital ' — in  other 
words,  by  ordinary  filtration,  diffusion  and  osmosis,  or  by  the  selec- 
tive action  of  living  cells  ?  In  the  case  of  the  digestive  juices  it 
has  been  seen  that  some  constituents  are  already  present  in  the 
blood,  but  that  physical  laws  alone,  so  far  as  we  at  present  under- 
stand them,  cannot  explain  the  proportions  in  which  they  occur  in 
the  secretions,  or  the  conditions  under  which  they  are  separated; 
while  other  constituents — and  these  the  more  specific  and  important 
— are  manufactured  in  the  gland-cells. 

In  the  kidneys  the  conditions  seem  at  first  sight  favourable  to 
physical  separation,  as  opposed  to  physiological  secretion.  Urine 
has  been  described  as  essentially  a  solution  of  urea  and  salts,  and 
both  are  ready  formed  in  the  blood.  The  arrangement  of  the  blood- 
vessels, too,  suggests  an  apparatus  for  filtering  under  pressure. 

Bloodvessels  and  Secreting  Tubules  of  Kidney. — The  renal  artery  splits 
up  at  the  hilus  into  several  branches,  which  pass  in  between  the  Mal- 
pighian  pyramids,  and  form  at  the  boundary  of  the  cortex  and  medulla 
vascular  arches,  from  which  spring,  on  the  one  side,  interlobular  arteries 
running  up  into  the  cortex  between  the  pyramids  of  Ferrein,  and,  on 
the  other,  vasa  recta  running  down  into  the  boundary  layer  of  the 
medulla  (Fig.  188).  The  interlobular  arteries  give  off  at  intervals 
afferent  vessels.  Each  of  these  soon  breaks  up  into  a  glomerulus  or  tuft 
of  vascular  loops,  which  gather  themselves  up  again  into  a  single 
efferent  vessel  of  somewhat  smaller  calibre  than  the  afferent.  The 
glomerulus  is  fitted  into  a  cup  or  capsule  (of  Bowman),  which  is  closely 
reflected  over  it,  except  where  the  afferent  and  efferent  vessels  pass 
through,  and  forms  the  beginning  of  a  urinary  tubule.  If  we  suppose 
the  tuft  pushed  into  the  blind  end  of  the  tubule  so  as  to  indent  it,  it  will 
be  easily  understood  that  the  single  layer  of  flattened  epithelium  reflected 
on  the  glomerulus  is  continuous  with  that  lining  the  capsule,  which  in 
its  turn  is  continuous  with  the  epithelial  layer  of  the  rest  of  the  urinary 
tubule.  This  has  been  divided  by  histologists  into  a  number  of  parts 
which  it  is  unnecessary  to  enumerate  here,  further  than  to  say  that  the 
urinary  tubule  proper  begins  in  the  cortex  in  Bowman's  capsule  and 
the  proximal  convoluted  tubule  (with  its  continuation,  the  spiral  tubule), 
and  ends  in  the  cortex  with  the  distal  convoluted  tubule,  the  connection 
between  the  two  being  made  by  a  long  loop  (Henle's)  with  a  descending 
and  an  ascending  limb  (Fig.  189).  Between  the  ascending  limb  and 
the  distal  convoluted  tube  is  interposed  the  zigzag  tubule.  The  tubule 
throughout  its  length  is  bounded  by  a  basement  membrane  lined  by  a 
single  layer  of  epithelium,  which  differs  in  its  character  in  different 
parts  of  the  tubule 


THE  SECRETION  OF  THE  URINE 


♦85 


Fig.  188. — Diagram  of  Blood- 
vessels of  Kidney  (Klein,  after 
Ludwig).  ai,  interlobular  ar- 
tery; vi,  interlobular  vein; 
g,  glomerulus,  to  wtiich  an 
afferent  artery  is  seen  coming 
from  the  interlobular  artery, 
and  from  which  an  efferent 
artery  proceeds  to  break  up 
into  a  capillary  net\vork  sur- 
rounding the  renal  tubules; 
vs,  vena  stellata;  ar,  arteriis 
rectae ;  vb,  leash  of  venae  rectae ; 
vp,  vascular  network  round 
ducts  at  ape.x  of  a  papilla. 


Fig.  189. — Diagram  of  Renal  Tubule  (Klein). 
A,  corte.x ;  a,  layer  of  cortex  immediately  under 
capsule  containing  no  Malpighian  corpuscles; 
a',  inner  layer  of  cortex  devoid  of  Malpighian  cor- 
puscles; B,  boundary  layer;  C,  papillary  zone  of 
medulla;  i.  Bowman's  capsule;  2,  neck  of  cap- 
sule; 3,  proximal  convoluted  tubule;  4,  spiral 
tubule;  5,  descending  part  of  Henle's  loop- 
tubule;  6,  the  loop;  7,  8,  and  9,  ascending  limb 
of  loop-tubule;  10,  irregular  tubule;  ir,  distal 
convoluted  tubule  ;  12.  junctional  tubule;  13, 
collecting  tubule  in  a  medullan,"  ray  ar  pyra- 
mid of  Ferrein;  14,  collecting  tubule  in  the 
boundary  layer;  15,  large  collecting  tubule 
ending  in  a  duct  of  Bellini. 


486 


EXCRETION 


The  distal  convoluted  tub:;  joins  by  means  of  the  short  connecting 
tubule  one  of  the  straight  tubules  which  form  the  pyramids  of  Ferrein 
or  medullary  rays  in  the  cortex,  and  which  run  down  into  the  medulla, 
always  unitmg  into  larger  and  larger  tubes  as  they  go,  until  at  length 
they  open  as  ducts  of  Bellini  on  the  apex  of  a  papilla.  The  two  convo- 
luted tubules  (with  the  spiral  and  zigzag  tubules)  are  lined  by  similar 
epithelial  cells  with  granular  contents,  and  the  tendency  of  the  granules 
to  be  arranged  in  rows  perpendicular  to  the  basement  membrane  gives 
them  a  striated  or  '  rodded  '  appearance  (Fig.  190).  The  granules  are 
eosinophile  (p.  17),  which  is  also  a  character  of  the  granules  of  other 
secreting  cells.     Towards  the  lumen  the  cells  may  show  a  brush  of  pro- 


Fig.  190. — From  a  Vertical  Section  of  Dog's  Kidney  to  show  the  Structure  of  Ditifereni 
Portions  of  the  Renal  Tubule  ( Klein) .  a,  B  owman's  capsule  enclosing  glomerulus, 
the  capillaries  of  which  are  arranged  in  lobules  separated  by  a  little  connective 
tissue.  The  capsule  and  glomerulus  together  constitute  a  Malpighian  body  or 
corpuscle;  n,  neck  of  capsule;  c,  c,  convoluted  tubules,  cut  in  various  directions; 
h,  irregular  or  zigzag  tubule;  d,  e,  and/ are  straight  tubules,  which  take  part  in  the 
formation  of  a  medullary  ray  or  pyramid  of  Ferrein ;  d,  collecting  tubule ;  e,  e,  spiral 
tubule;  /,  narrow  part  of  ascending  limb  of  Henle's  loop -tubule;  b,  c,  and  e  are 
lined  with  rodded  epithelium. 

cesses,  looking  like  cilia,  but  in  mammals  these  are  not  motile.  The 
ascending  part  of  Henle's  loop  also  has  cells  of  the  same  general  char- 
acter, with  numerous  granules,  although  the  '  rodding  '  may  not  be  so 
distinct.  We  shall  see  directly  that  the  morphological  resemblance  is 
the  index  of  a  functional  likeness.  The  blood-supply  of  the  tubules, 
especially  of  the  convoluted  portions,  is  exceedingly  rich,  the  efferent 
vessels  of  the  glomeruli  breaking  up  around  them  into  a  close-meshed 
network  of  capillaries,  from  which  the  blood  is  collected  into  inter- 
lobular veins  running  parallel  to  the  interlobular  arteries  between  the- 
pyramids  of  Ferrein.  The  straight  tubules  of  the  medulla  are  also 
surrounded   by  capillanes   given   off   from   straight   arteries    (arteriae 


THE  SECRETION  OF  THE  URINE  487 

rectaj)  running  down  into  it  partly  from  the  arterial  arches  and  partly 
from  efferent  ve'ssels  of  the  glomeruli  nearest  the  boundary  layer,  the 
blood  passing  away  by  straight  veins  (venas  rectaj)  which  join  the  larger 
veins  accompanying  the  arterial  arches.  The  greater  part  of  the 
blood  going  through  the  kidney  has  to  pass  through  two  sets  of  capil- 
laries, one  in  the  glomeruli,  the  other  around  the  tubules.  Even  the 
portion  of  it  which  does  not  go  through  the  glomeruli  has  for  the  most 
part  a  long  route  to  traverse  in  narrow  arterioles  and  venules  to  and 
from  its  capillary  distribution.  And  the  mean  circulation-time  through 
the  kidney  has  been  found  to  be  longer  than  that  through  most  other 
organs  (p.  137). 

Theories  of  Renal  Secretion. — To  come  back  to  our  problem  of 
the  nature  of  renal  secretion,  the  anatomical  structure  of  the  kidney 
might  be  expected  to  throw  light  upon  the  question.  And,  indeed, 
it  was  on  a  purely  histological  foundation  that  Bowman  established 
his  famous  *  vital  '  theory  of  renal  secretion.  Impressed  with  the 
resemblance  between  the  renal  epithelium  and  the  epithelial  cells 
of  other  glands,  and  with  the  distribution  of  the  bloodvessels  in  the 
kidney,  he  came  to  the  conclusion  that  the  characteristic  con- 
stituents of  urine,  including  urea,  were  secreted  from  the  blood  by 
the  tubules.  To  the  Malpighian  bodies  he  assigned  what  he  doubt- 
less considered  the  humbler  office  of  separating  water  from  the 
blood  for  the  solution  of  the  all-important  solids.  To  Ludwig,  on 
the  other  hand,  with  his  whole  attention  fastened  on  the  mechanical 
factors  by  which  the  flow  of  urine  could  be  influenced,  the  tubules 
seemed  of  secondary  importance,  while  the  glomeruli  appeared  a 
complete  apparatus  for  filtering  urine  from  the  blood  into  Bow- 
man's capsule.  He  saw  that  the  efferent  vessel  was  smaller  than 
the  afferent ;  that  it  was  therefore  easier  for  blood  to  come  to  the 
glomerulus  than  to  get  away  from  it,  and  that  the  pressure  in  the 
capillaries  of  the  tuft  must  be  higher  than  in  ordinary  capillaries, 
because  the  resistance  beyond  them  in  the  comparatively  narrow 
efferent  vessel,  and  especially  in  the  second  plexus,  is  greater  than 
the  resistance  beyond  a  single  capillary  network.  And  experi- 
mental investigation  soon  showed  him  that  the  rate  at  which  urine 
was  formed  could  be  greatly  influenced  by  changes  in  the  blood- 
pressure. 

On  such  considerations,  Ludwig  founded  the  '  mechanical  '  theory 
of  urinary  secretion,  which,  although  in  a  much  modified  form,  still 
divides  with  the  '  vital  '  theory  the  allegiance  of  physiologists. 
It  is  impossible  here  to  enter  in  detail  into  a  controversy  that  has 
extended  over  more  than  half  a  century  and  produced  an  extensive 
literature.  The  result  of  the  discussion  has  been,  in  our  opinion, 
to  estabhsh  in  its  essential  principles  the  '  vital '  theory  of  Bowman, 
or  at  least  to  show  that  no  purely  physico-chemical  theory  as  yet 
constructed  will  account  for  all  the  facts. 

Ludwig  supposed  that  the  urine,  qualitatively  complete  in  all  its 
constituents,  was  simply  filtered  through  the  glomeruli,  the  work 


488  EXCRETION 

done  in  this  filtration  being  performed  entirely  at^the  expense  of 
the  energy  of  the  heart -beat  represented  as  lateral  pressure  in  the 
vessels  of  the  tiifts.  But  as  the  proportion  of  salts,  and  especially 
of  urea,  is  very  far  from  being  the  same  in  urine  as  in  blood,  it  had 
further  to  be  assumed  that  the  liquid  which  passes  into  Bowman's 
capsule  is  exceedingly  dilute,  and  that  absorption  of  water,  and 
perhaps  of  other  constituents,  takes  place  in  its  passage  along  the 
renal  tubules.  This  process  of  reabsorption  he  pictured  as  a  purely 
physical  diffusion  between  the  dilute  urine  in  contact  with  the  free 
ends  of  the  epithelial  cells  lining  the  tubules  and  the  much  more 
concentrated  lymph  with  which  their  deep  ends  are  bathed.  The 
great  length  of  these  tubules,  as  compared  with  those  of  most  other 
glands,  might  indeed  seem  to  indicate  a  long  sojourn  of  the  urine 
in  them,  and  the  probability  of  important  changes  being  caused  in 
its  passage  along  them.  But  if  we  consider  the  immense  length 
(60  to  70  cm.)  of  the  seminal  tubules  and  of  their  gigantic  ducts 
(epididymis  6  metres);  where,  of  course,  absorption  of  water  on  a 
large  scale  is  out  of  the  question,  it  will  be  granted  that  little  can 
be  built  upon  the  mere  length  of  the  renal  tubules.  On  the  other 
hand,  the  salivary  glands,  where  there  are  no  glomeruli,  secrete  as 
much  water  as  the  kidneys  are  supposed  to  filter ;  and  the  pancreas, 
whose  capillaries  form  the  first  of  a  double  set,  and  therefore  in  this 
respect  correspond  to  the  renal  glomeruli,  secretes  less  water  than 
the  liver,  whose  capillaries  correspond  to  the  low-pressure  plexus 
around  the  convoluted  tubules  of  the  kidney.  So  that  deductions 
drawn  from  the  anatomical  relations  of  the  bloodvessels  are  not  in 
this  case  of  much  value,  unless  supported  by  physiological  results. 

It  is  somewhat  unfortunate  that  systematic  writers  have  fallen 
into  the  habit  of  discussing  the  mechanisrii  of  urinary  secretion  as 
if  the  Ludwig  theory  and  the  Bowman  theory  presented  an  exact 
antithesis,  as  if  the  one  offered  a  complete  '  mechanical  '  explana- 
tion of  a  process,  which  the  other  viewed  as  entirely  '  vital,'  and 
therefore  withdrawn  from  physical  explanation. 

We  need  not  concern  ourselves  here  with  the  historical  develop- 
ment of  this  discussion.     Three  main  questions  require  our  attention : 

1.  Is  there  any  evidence  that  reabsorption  actually  occurs  in  the 
tubules  ?  If  reabsorption  on  an  important  scale  does  take  place,  it 
follows  at  once  that  there  must  be  a  difference  of  function  between 
the  two  parts  of  the  renal  apparatus,  through  which  urinary  con- 
stituents pass  in  opposite  directions. 

2.  But  if  there  is  no  reabsorption,  or  none  of  importance,  it  may 
still  be  asked  whether,  the  direction  of  movement  of  the  urinary 
constituents  through  the  glomeruli  and  the  tubular  epithelium  being 
the  same,  some  quantitative  or  qualitative  difference  in  their 
activity  may  not  exist,  certain  constituents,  e.g.,  passing  mainly  or 
exclusively  through  the  one  or  the  other. 


THE  SECRETION  OF  THE  URINE  489 

3.  When  these  questions  have  been  settled,  we  are  in  a  position 
to  consider  the  nature  of  the  process  by  which  the  urinary  con- 
stituents find  their  way  from  the  blood  into  the  lumen  of  the 
capsules  and  the  tubules,  or,  if  there  is  reabsorption,  out  of  the 
tubules  into  the  lymph  and  blood  again,  and  to  see  whether  or  no 
it  can  be  entirely  explained  on  mechanical  and  physico-chemical 
principles. 

The  Question  of  Reabsorption  from  the  Tubules. — That  some 
absorption  can  take  place  from  the  kidney  when  the  pressure  in 
the  ureter  is  abnormally  raised  need  not  be  doubted,  and  when 
substances  like  potassium  iodide  or  strychnine  are  introduced  into 
the  ureter  or  the  pelvis  of  the  kidney  under  these  circumstances, 
they  can  speedily  be  detected  in  the  blood.  When  the  ureter 
pressure  (in  dogs)  is  only  slightl}^  increased,  instead  of  evidence  of 
reabsorption,  we  obtain  evidence  of  increased  secretion.  The 
volume  of  urine,  the  total  quantity  of  sulphate  in  the  urine  when 
sodium  sulphate  i=  injected  into  the  blood  as  a  diuretic,  and  the 
total  amount  of  reducing  sugar  when  phlorhizin  is  injected,  are  all 
greater  on  the  obstructed  than  on  the  normal  side.  These  facts  are 
quite  opposed  to  the  idea  that  filtration  and  reabsorption  are  im- 
portant factors  in  the  preparation  of  normal  urine  (Brodie  and 
CuUis).  Changes  in  the  blood- flow  through  the  kidney  have  nothing 
to  do  with  the  results,  since  the  small  increase  in  pressure  in  the 
ureter  was  shown  not  to  affect  the  rate  of  flow  of  the  blood.  The 
attempt  has  been  made  to  decide  whether  absorption  normally 
ocrurs  by  removing  as  much  of  the  tubules  as  possible,  and  seeing 
whether  the  character  of  the  urine  is  altered.  In  rabbits  the  whole 
or  a  large  portion  of  the  medulla  has  been  excised  from  one  kidney 
and  the  other  then  extirpated.  From  the  mutilated  kidney  two  or 
three  times  as  much  urine  was  said  to  flow  as  was  secreted  by  a 
control  rabbit  operated  on  in  the  same  way,  except  for  the  removal 
of  the  renal  medulla  (Ribbert).  The  conclusion  was  drawn  that 
the  greater  quantity  of  urine  escaping  was  due  to  the  smaller 
opportunity  for  reabsorption  of  the  water.  But  experiments  men- 
tioned on  p.  649  suggest  a  different  interpretation  of  these  observa- 
tions. And  Bo3^d,  who  repeated  Ribbert 's  work,  obtained  quite 
different  results  after  partial  removal  of  the  medulla.  He  found 
it  impossible  to  remove  the  whole.  So  that  hitherto  the  direct 
method  of  eliminating  the  tubules  has  left  the  matter  where  it  was. 
Some  light  has  been  thrown  on  this  question,  by  taking  advantage 
of  the  anatomical  fact  that  the  kidney  of  batrachians,  and,  indeed, 
that  of  fishes  and  ophidia  as  well,  has  a  double  blood-supply.  The 
renal  artery  gives  off  afferent  vessels  to  the  glomeruli ;  the  vena 
advehens,  or  renal  portal  vein,  breaks  up,  like  the  portal  vein  in  the 
liver,  into  a  plexus  of  capillaries  surrounding  the  tubules,  and  there 
seems  to  be  no  communication  between  the  two  vascular  svstems. 


490 


EXCRETION 


By  tying  all  the  arteries  going  to  the  kidneys  in  frogs  the  circula- 
tion through  the  glomeruli  can  be  completely  cut  off,  while  ligation 
of  the  renal  portal  vein  does  not  affect  the  blood-supply  of  the 
glomeruli,  though  markedly  interfering  with  that  of  the  tubules. 
Gurwitsch  has  found  that,  after  ligation  of  the  renal  portal  vein  of 
one  kidney  in  (male)  frogs,  the  flow  of  urine  from  that  kidney  is 
much  diminished  as  compared  with  the  other.  He  argues  that  if 
reabsorption  of  dilute  urine  filtered  through  the  glomeruli  takes 
place  in  the  tubules,  the  opposite  result  ought  to  be  obtained,  since 
the  glomeruli  are  not  affected,  while  any  absorptive  power  of  the 
tubules  must  be  crippled  or  abolished. 

Experiments  on  the  Excretion  of  Pigments  by  the  Kidney. — In 
connection  with  the  second  question,  and  also  incidentally  with  the 
first,  the  results  of  experiments  on  the  distribution  of  pigments  in 

the  kidney  after  their  injection  into 
the  blood  have  often  been  appealed  to. 
Heidenhain  injected  indigo  -  carmine 
into  the  blood  of  rabbits,  and  after  a 
variable  time  killed  them,  cut  out  the 
kidneys,  and  flushed  them  with  alcohol, 
in  which  the  pigment  is  insoluble.  His 
results  were  as  follows:  (i)  When  the 
Fig.  191.— Diagram  of  Distribu-  gpi^al  cord  was  CUt  before  the  injec- 
tion of  Pigment  m  Kidney  after  ,f  .  ,  ,  1  .1  11  J 
Injection  into  Blood.  The  cor-  tion  m  order  to  reduce  the  blood- 
tex  between  a  and  h  and  be-  pressure,  the  blue  granules  were  found 
tween  c  and  d  was  cauterized  j^  the  '  rodded  '  epithelium  of  the 
before   the   injection.      In  the                   1    j     i  j^    •■     1             i   .  i  j- 

blank  wedge-shaped  portions,  i.  convoluted  tubules  and  the  ascendmg 
there  was  no  pigment.  In  the  limb  of  Henle's  loop,  and  in  the  lumen 
zones  shaded  like  2  there  was    ^f    ^he    tubules,    but    nowhere    else. 

some  pigment,  but  not  so  much      -r-,  ,  i  1.   •       j 

as  in  the  areas  shaded  like  3.  Bowman  s  capsules  contamed  no  pig- 
ment. The  renal  cortex  was  coloured 
blue.  {2)  When  the  spinal  cord  was  not  cut,  the  pigment  was  found 
in  the  medulla  and  pelvis  of  the  kidney,  as  well  as  in  the  cortex, 
but  always  in  the  lumen  of  the  tubules,  and  not  in  the  epithelium, 
except  in  the  situations  mentioned.  (3)  If  a  portion  of  the  cortex 
of  the  kidney  had  been  cauterized  with  nitrate  of  silver  before  in- 
jection of  the  pigment,  the  spinal  cord  being  left  intact,  a  wedge  of 
the  renal  substance,  corresponding  to  this  area,  remained  coloured 
only  in  the  cortex,  although  the  rest  was  blue  in  the  medulla 
also.  The  '  rodded  '  epithelium  was  filled  with  blue  granules  as 
before  (Fig.  191). 

(i)  shows  that  the  epithelium  is  capable  of  excreting  some  sub- 
stances at  least.  (2)  appears  to  show  that  when  the  blood-pressure 
is  normal  water  is  poured  out  from  some  part  of  the  tubule,  and 
washes  the  pigment  separated  by  the  '  rodded  '  epithelium  down 
towards  the  papillae.      (3)  suggests  that  it  is  through  the  glomeruli 


THE  SECRETION  OF  THE  URINE  491 

that  most  of  the  water  passes.  For  cauterization  has  not  destroyed 
the  power  of  the  epithehum  to  excrete  pigment,  and  therefore, 
presumably,  would  not  have  destroyed  its  power  to  excrete  water 
if  it  possessed  this  power  in  any  great  degree;  and  the  glomeruh 
and  their  capsules  are  the  only  other  part  of  the  renal  mechanism 
which  can  have  been  affected.  The  fact  that  in  birds  and  serpents, 
whose  urine  is  solid  or  semi-solid,  the  glomeruli  are  smaller  than  in 
mammals  is  corroborative  evidence  that  the  glomeruli  have  to  do 
with  the  excretion  of  water. 

When  pigments  are  injected  into  the  dorsal  lymph- sac  of  a  frog 
without  interference  with  the  renal  circulation,  they  are  found 
pl(?htifully  in  the  lumen  of  the  convoluted  tubules,  and  also  in  the 
epithelial  cells  lining  them.  The  suggestion  has  been  made  that 
the  pigments  have  been  absorbed  by  the  cells  from  the  lumen,  and 
not  excreted  by  them  into  it.  And  certainly  pigments  soluble  in 
the  cytoplasm  or  in  the  substances  that  form  the  envelopes  of  cells, 
and  therefore  capable,  like  methylene  blue,  of  staining  them  during 
life,  might  be  taken  up  by  the  renal  epithelium  if  excreted  into  the 
tubules  by  the  glomeruli,  and  might  cause  staining  of  them,  par- 
ticularly, of  course,  of  the  free  ends  of  the  cells  next  the  lumen. 
But  this  suggestion  is  inadmissible,  since,  on  injection  of  the  same 
pigments  after  ligation  of  the  renal  portal  vein,  the  convoluted 
tubules  contain  little  or  no  pigment  in  their  lumen.  And  when  the 
urinary  flow  is  stopped  on  one  side  in  mammals  by  temporary  com- 
pression of  the  renal  artery,  the  corresponding  kidney  takes  up  fully 
as  much  carmine  as  its  fellow  (Carter).  There  is  no  doubt  that  not 
only  pigments  capable  of  '  vital  staining,'  like  methylene  blue,  but 
also  pigments  which  do  not  stain  living  cells,  are  taken  up  from 
the  blood  (or  lymph)  by  the  epithelial  cells,  and,  lying  in  vacuoles 
in  their  cj^toplasm,  are  transported  towards  the  lumen,  and  there 
extruded.  It  is  not  the  solubility  of  the  pigments  in  lipoids,  and 
therefore  their  solubility  in  the  supposed  lipoid  envelope  of  the  cells, 
which  determines  whether  they  shall  be  excreted.  The  degree  in 
which  they  are  capable  of  being  presented  to  the  cells  in  non-colloid 
solution  appears  to  some  extent  to  be  a  determining  factor.  The 
pigments  not  taken  up  are  highly  colloidal  (Gurwitsch,  Hober). 
Shafer  has  recently  confirmed  Heidenhain's  statements  as  to  the 
place  of  excretion  of  indigo-carmine.  When  leuco-indigo-carmine 
(a  colourless  reduction-product  of  indigo-carmine)  was  injected,  the 
blue  oxidized  substance  was  found  in  the  lumen  of  the  convoluted 
tubules  and  in  the  collecting  tubules,  but  not  at  all  in  the  Bow- 
man's capsule.  The  cells  of  the  convoluted  tubules  were  colour- 
less, because  they  kept  the  pigment  in  its  reduced  condition,  and  it 
only  became  oxidized  in  the  lumina  of  those  parts  of  the  tubules 
whose  contents,  according  to  Dreser,  show  an  acid  reaction.  On  oxi- 
dation by  peroxide  of  hydrogen  the  cells  of  the  convoluted  tubules 


492 


EXCRETION 


became  faintly  green,  but  the  Bowman's  capsule  remained  colourless. 
This  can  only  be  explained  on  the  assumption  that  the  leuco-product 
of  the  pigment  was  excreted  by  the  cells  of  the  convoluted  tubules. 

But  these  cells  are  far  from  taking  up  all  pigments  indifferently. 
Some  pigments  are  extruded  mainly  by  one  part,  others  mainly  by 
another  part,  of  the  renal  tubule,  and  some  even  by  the  glomeruli, 
as  shown  long  ago  for  ammonium  carminate.  The  glomeruli,  how- 
ever, are  in  general  far  less  active  in  this  regard  than  the  epithehal 
cells,  and  the  fact  that  the  latter  pick  out  from  the  blood  such  sub- 
stances as  these  foreign  pigments,  which  pass  through  the  Mal- 
pighian  tufts  unchallenged,  renders  it  likely  that  the  tubules  also 
exercise  a  special  function  in  the  secretion  of  the  normal  con- 
stituents of  m-ine.  More  direct  evidence  of  this  is  not  wanting, 
for  Bowman  saw  crystals  of  uric  acid  in  the  epithelium  of  the 
convoluted  tubules  of  birds.  Heidenhain  found  that  urate  of  soda 
injected  into  the  blood  of  a  rabbit  is  excreted  by  the  epithelium  of 
the  convoluted  tubules  and  the  ascending  part  of  Henle's  loop, 
just  as  is  the  case  with  indigo-carmine.  And  Nussbaum's  experi- 
ments, although  not  quite  conclusive,  have  made  it  probable  that 
in  the  frog  urea  is  actually  separated  by  the  epithelium  of  the 
tubules.  They  were  founded  on  the  anatomical  peculiarity  in  the 
renal  circulation  of  the  frog  already  mentioned.  By  tying  the  renal 
arteries  in  that  animal,  he  thought  he  could  at  will  stop  the  circula- 
tion in  the  glomeruli,  and  he  foimd  that  after  this  was  done  there 
was  no  further  spontaneous  secretion  of  urine.  But  when  urea  was 
injected  intravenously  the  secretion  of  urine  again  began,  urea 
being  eliminated  by  the  kidneys,  and  water  along  with  it.  Sugar, 
peptone,  and  egg-albumin,  injected  into  the  blood,  no  longer  passed 
into  the  urine,  even  when  the  secretion  was  excited  by  simultaneous 
injection  of  urea,  although  they  readily  did  so  when  the  arteries 
were  not  tied.  He  concluded  that  the  Malpighian  corpuscles  have 
the  power  of  excreting  water,  sugar,  peptone,  and  albumin,  while 
the  epithelium  of  the  tubules  excretes  urea  as  well  as  water. 

Beddard  has  confirmed  Nussbaum's  statement  that  when  all  the 
arteries  going  to  the  kidney  are  tied  the  glomeruli  are  completely 
and  permanently  deprived  of  blood.  The  spontaneous  secretion 
of  urine  is  totally  stopped,  as  Nussbaum  found,  but  only  in  three 
experiments  out  of  eighteen  was  it  possible  to  start  the  secretion 
by  injection  of  urea.  The  epithelium  of  the  tubules  degenerated 
and  desquamated  after  complete  ligation  of  all  the  renal  arteries, 
showing  that  it  requires  some  arterial  blood  as  well  as  the  venous 
blood  from  the  renal  portal  to  maintain  its  vitality.  The  degenera- 
tion of  the  epithelium  can  be  prevented  by  keeping  the  frogs  in  an 
atmosphere  of  oxygen  after  ligation  of  the  arteries.  In  six  such 
frogs,  in  which  the  complete  elimination  of  the  glomeruli  was  con- 
trolled by  subsequent  injection,   secretion   of   urine  followed  the 


THE  SECRETION  OF  THE  URINE  493 

injection  of  urea,  alone  or  in  combination  with  dextrose,  phlorhizin, 
or  di-sodium  hydrogen  phosphate  (Na2HP04).  In  all  the  cases  the 
urine  contained  urea,  chlorides,  and  sulphates,  and  was  acid  to 
phenolphthalein.  In  one  case  after  injection  of  urea  and  dextrose, 
and  in  another  after  urea  and  phlorhizin,  the  urine  reduced  Fehling's 
solution,  and  therefore  presumably  contained  dextrose  (Beddard 
and  Bainbridgc).  When  the  frog's  kidney  is  perfused  in  situ  with 
oxygenated  salt  solution  a  certain  flow  of  urine  takes  place.  Sub- 
stitution of  non-oxygenated  saline  markedly  slows  the  flow  (CuUis). 

Apparently,  then,  the  tubules  have  the  capacity  to  secrete  prac- 
tically all  the  constituents  of  urine,  and  when  the  flow  of  urine  is 
small,  probably  most  of  it  comes  from  the  tubules.  When,  as  in 
the  diuresis  produced  by  salt  solutions,  large  quantities  of  water 
and  salts  have  to  be  rapidly  excreted,  the  bulk  of  the  liquid  comes 
from  the  glomeruli,  but  also  by  a  process  of  secretion. 

Lindemann  has  endeavoured  to  exclude  the  glomeruli  in  mam- 
mals by  injecting  oil  through  the  renal  artery.  After  a  short  time, 
according  to  him,  the  oil  emboli  clear  away  from  practically  all 
parts  of  the  kidney  except  the  glomeruli,  which  remain  plugged. 
If  indigo-carmine  be  subsequently  injected  into  the  blood,  it  is  not 
only  taken  up  from  it  by  the  embolized  kidney  as  well  as  by  a  normal 
one,  but  is  excreted.  The  quantity  of  urine  is  much  diminished, 
and  its  specific  gravity  increased,  but  its  composition  is  not  essen- 
tially altered.  He  infers  that  the  tubules  are  in  a  high  degree 
independent  of  the  glomeruli  as  an  apparatus  for  the  secretion  of 
urine.  More  conclusive  observations  have  lately  been  reported  in 
which  the  tubules  were  eliminated  by  producing  an  artificial  nephritis 
in  rabbits  by  the  subcutaneous  injection  of  sodium  tartrate.  Tar- 
trates act  almost  specifically  upon  the  tubules,  causing  no  noticeable 
effect  upon  the  glomeruli.  After  the  intravenous  infusion  of  a 
solution  containing  sodium  chloride  and  urea  during  pronounced 
tartrate  nephritis,  all  the  chlorine  appears  in  the  urine  within  forty- 
eight  hours,  but  little,  if  any,  of  the  urea.  In  the  light  of  the 
histological  findings,  this  is  interpreted  to  mean  that  under  normal 
conditions  chlorides  and  water  are  passed  through  the  glomerular 
mechanism,  and  urea  tlirough  the  convoluted  tubules  (Underbill, 
Wells,  and  Goldschmidt).  These  results  constitute  a  direct  and 
striking  confirmation  of  the  Bowman  hypothesis. 

As  regards  our  first  two  questions,  we  may  conclude  that  there  is 
no  good  evidence  tliat  reabsorption  of  water  or  other  constituents  of  the 
urine  in  the  renal  tubules  plays  an  important  part  in  th^  preparation 
of  that  secretion.  Many  facts  favour  the  conclusion  that  the  glomeruli 
and  the  renal  epithelium  act  as  distinct,  although,  of  course,  mutually 
supplementary  mechanisms,  the  glomeruli  separating  the  larger  portion 
of  the  water  and  salts,  the  epithelium  the  larger  portion,  if  not  the 
whole,  of  the  characteristic  organic  constituents. 


494  EXCRETION 

As  regards  the  third  question,  it  is  now  generally  admitted,  even 
by  those  who  uphold  a  modified  '  mechanical '  theory,  that  if 
the  urine  is  originally  separated  from  the  blood  by  filtration  at  the 
expense  of  the  energy  of  the  heart-beat  represented  by  the  pressure 
of  the  blood  in  the  glomeruli,  the  reabsorption  in  the  tubules  cannot 
be  attributed  to  simple  diffusion,  but  must  be  a  selective  process 
analogous  to  absorption  in  the  intestine  and  entailing  the  expendi- 
ture of  a  large  amount  of  work  at  the  expense  of  the  food  materials 
or  the  protoplasm  of  the  epithelial  cells.  Every  attempt  at  a 
strictly  mechanical  explanation  breaks  down  for  the  kidney,  as  for 
other  glands. 

The  practical  absence  from  urine  of  the  proteins  and  sugar  of  the 
blood  under  normal  circumstances,  and  the  elimination  by  the 
kidney  of  egg-albumin,  peptone,  and  other  bodies  when  injected 
into  the  veins,  show  a  selective  permeability  inexplicable  by  refer- 
ence to  any  known  structural  or  physico-chemical  property  of  the 
renal  epithelium  or  the  glomeruli,  but  precisely  the  kind  of  thing 
which  the  physiologist  has,  without  being  hitherto  able  to  explain 
it,  learnt  to  associate  with  the  activity  of  living  cells.  Urea  and 
dextrose,  both  highly  diffusible  substances,  circulate  side  by  side 
in  the  bloodvessels  of  the  kidney.  The  one  is  taken  and  the  other 
left.  The  urea  is  a  waste-product  of  no  further  use  in  the  economy. 
The  sugar  is  a  valuable  food- substance.  The  kidney  selects  with 
unerring  certainty  the  urea,  of  which  only  4  parts  in  10,000  are 
present  in  the  blood,  but  rejects  the  sugar,  of  which  there  is  three 
times  as  much.  The  theory  that  the  dextrose  of  the  blood  or  a 
part  of  it  is  combined  with  substances  in  the  colloid  state,  and  not 
in  ordinary  solution,  has  been  advanced  from  time  to  time  as  an 
explanation  of  the  practical  impermeability  of  the  kidney  for  this 
sugar  under  normal  conditions.  But  no  proof  of  the  truth  of  this 
hypothesis  has  ever  been  given.  On  the  contrary,  there  is  good 
evidence  that  all  the  dextrose  which  is  estimated  in  blood  by 
analytical  methods  is  in  the  free  condition.  For  instance,  dextrose 
easily  escapes  from  blood  circulating  in  the  vivi-di0usion  apparatus 
previously  described  (p.  48) .  And  when  the  plasma  of  shed  blood  is 
placed  in  a  dialyser  tube  of  animal  membrane  surrounded  by  a  liquid 
in  which  dextrose  is  dissolved  in  exactly  the  same  concentration  as 
that  determined  in  the  plasma  by  the  ordinary  chemical  methods, 
the  contents  of  the  dialyser  neither  lose  nor  gain  dextrose.  Now, 
the  plasma  ought  to  gain  sugar  by  diffusion  if  a  portion  of  the 
dextrose  in  it  exists  in  a  combination  which  prevents  its  diffusion, 
just  as  it  does  gain  dextrose  when  the  liquid  outside  the  dialyser 
contains  sugar  in  greater  concentration  than  the  plasma  (Michaelis 
and  Rona). 

Egg-albumin  injected  into  the  blood  passes  through  the  renal 
circulation  side  by  side  with  the  serum-albumin  of  the  plasma. 


THE  SECRETION  OF  THE  URINE  495 

Both  are  indiffusible  through  membranes,  and  to  the  physical 
chemist  the  differences  between  them  may  appear  superficial  and 
minute.  But  the  kidney  does  not  hesitate  for  an  instant.  A  large 
part  of  the  egg-albumin  is  promptly  excreted  as  a  foreign  substance; 
the  serum-albumin  passes  on  untouched. 

Not  only  does  the  kidney  exercise  a  power  of  qualitative  selec- 
tion; it  also  takes  cognizance  of  the  quantitative  composition  of 
the  blood.  So  long  as  there  is  less  sugar  in  the  plasma  than  about 
1-5  to  2  parts  in  1,000,  it  is  refused  passage  into  the  renal  tubules. 
But  when  this  limit  is  passed,  and  the  proportion  of  sugar  in  the 
blood  becomes  excessive,  the  kidney  begins  to  excrete  sugar,  and 
continues  to  do  so  till  the  balance  is  redressed. 

The  advocates  of  the  theory  of  filtration  through  the  glomeruli 
under  the  influence  of  the  difference  of  hydrostatic  pressure  in  the 
capillaries  and  in  the  lumen  of  the  capsules  have  made  their  firmest 
stand  on  the  excretion  of  the  inorganic  constituents  of  the  urine. 
They  have  laid  stress  particularly  on  the  fact  that  the  hydraemic 
plethora  caused  by  intravenous  injection  of  salts  is  accompanied 
by  diuresis.  It  is  true  that  the  direct  introduction  of  water  into 
the  blood,  or  its  attraction  from  the  lymph-spaces  when  the  osmotic 
pressure  of  the  blood  is  increased  by  the  injection  of  substances  like 
urea,  sugar,  and  sodium  chloride,  may  cause  a  condition  of  hydrcemic 
plethora,  and  that  this  plethora  may  sometimes  be  associated  with 
an  increase  of  pressure  in  the  capillaries  in  general,  and  therefore 
in  the  vessels  of  the  Malpighian  tuft.  It  may  also  be  admitted  that 
such  an  increase  of  pressure  might  be  accompanied  by  an  increased 
filtration  of  water  and  salts  into  Bowman's  capsule.  Even  in  the 
excised  kidney,  after  the  vital  activity  of  its  cells  may  be  presumed 
to  have  ceased,  filtration  of  the  most  varied  solutions  occurs  when 
the  organ  is  perfused  with  them  through  the  renal  artery.  The 
liquid  which  escapes  from  the  ureter  always  has  the  same  composi- 
tion as  the  perfusion  fluid  (SoUmann).  It  would  certainly  appear 
unlikely  that  the  glomerular  epithelium  should  make  no  use  what- 
ever for  the  furtherance  of  its  task  of  the  difference  of  hydrostatic 
pressure  on  its  two  surfaces.  It  is  in  taking  advantage  of  such 
circumsta  ces  for  the  promotion  of  its  specific  work  up  to  the 
point  at  which  they  cease  to  favour  it  that  a  great  part  of  the  true 
secretory  activity  of  cells  may  be  supposed  to  consist,  ^^'hen  we 
see  a  barge  passing  through  a  lock,  and  being  gradually  lifted  to 
the  proper  level  by  the  inrush  of  water,  we  never  dream  of  saying 
that  the  whole  thing  is  an  affair  of  the  laws  of  hydrostatics.  We 
know  that  the  part  played  by  the  lock-keeper,  the  opening  and 
closing  of  the  gates  and  sluices  at  the  proper  time,  is  all-important, 
although  he  does  not  lighten  by  one  ounce  the  weight  which  the 
water  must  lift.  He  uses  the  head  of  water  for  a  specific  purpose 
— namely,  to  lift  the  barge.     In  like  manner  it  is  to  be  expected 


496  EXCRETION 

that  the  glomerular  epithelium,  when  the  difference  of  pressure 
on  its  two  surfaces  is  increased  by  hydrgemic  plethora,  will  use  the 
increased  facility  of  filtration  to  rapidly  excrete  a  portion  of  the 
water.  But  who  will  believe  that  the  addition  of  a  tumbler  of 
water,  absorbed  from  the  ahmentary  canal,  to  4  or  5  litres  of  blood 
circulating  in  a  system  of  vessels  whose  capacity  can  and  does  vary 
within  wide  limits,  should  cause  in  the  capillaries  of  the  kidney 
an  increase  of  pressure  exactly  proportional  to  the  increase  in  the 
elimination  of  water  in  the  urine,  lasting  for  the  same  time  and 
disappearing  at  the  moment  when  the  normal  composition  of  the 
blood  is  restored  ?  Nor  is  it  easier  to  explain  on  any  mechanical 
hypothesis  how  it  is  that  in  a  starving  animal  the  quantity  of 
inorganic  substances  eliminated  in  the  urine  drops  almost  to  zero, 
while  the  proportional  amount  in  the  blood  and  tissues  is  little,  if 
at  all,  affected.  In  a  rabbit  rendered  poor  in  sodium  chloride  by 
feeding  it  with  salt-free  food,  the  injection  of  a  solution  of  sodium 
chloride  isotonic  with  the  blood  produces  no  diuresis  for  a  con- 
siderable time,  but,  on  the  contrary,  a  diminished  flow  of  urine, 
while  a  similar  solution  injected  into  the  veins  of  a  rabbit  previously 
fed  with  salted  food  causes  an  immediate  and  considerable  diuresis. 
When  small  quantities  of  isotonic  solutions  of  various  salts  are 
injected,  those  not  normally  present  in  the  blood  produce  a  greater 
diuresis  than  normal  constituents.  Sodium  chloride,  which  is 
present  in  normal  plasma  in  greater  amount  than  any  other  salt, 
causes  the  smallest  diuresis  of  all  (Haake  and  Spiro). 

Such  facts  suggest  that  the  secreting  cells  of  the  kidney  are  stimu- 
lated or  inhibited  by  the  contact  of  blood  or  lymph  in  which  the 
normal  constituents  are  present  in  too  great  or  in  too  small  amount, 
and  that  the  intensity  of  the  action  is  proportional  to  the  degree  of 
deficiency  or  excess.  The  greater  the  velocity  of  the  circulation 
in  the  kidney,  the  more  effective  will  be  the  stimulation  produced 
by  any  given  substance  present  in  excess,  and  therefore  the  greater 
the  total  amount  of  it  eliminated  in  a  given  time.  For  in  making 
the  round  of  the  renal  circulation  the  concentration  of  the  sub- 
stance in  any  given  portion  of  blood  will  fall  less,  and  therefore  the 
average  stimulation  exerted  by  it  during  the  round  will  be  greater 
the  faster  the  blood  flows.  It  is  quite  in  agreement  with  this  that 
when  plethora  is  occasioned  by  transfusion  of  blood  there  is  little 
or  no  diuresis,  although  the  increase  of  arterial,  capillary,  and 
venous  pressure,  and  the  dilatation  of  the  kidney,  are  evident. 
For  the  rapid  passage  of  liquid  out  of  the  vessels  would  lead  to  a 
great  increase  in  the  relative  proportion  of  corpuscles  to  plasma — 
that  is  to  say,  to  an  abnormal  condition  of  the  blood.  On  the  other 
hand,  when  plethora  is  produced  by  injection  of  serum  diuresis 
occurs  (Cushny).  This,  again,  is  what  we  should  expect,  since  the 
elimination  of  the  superfluous  liquid  will  restore  the  normal  pro- 


THE  SECRETION  OF  THE  URINE  497 

portion.  The  diminished  viscosity  of  the  blood  (p.  23)  produced 
by  the  excess  of  serum  will  aid  the  flow  through  the  kidney  and 
therefore  increase  the  diuresis,  while  in  the  case  of  the  plethora 
produced  by  injection  of  blood  the  elimination  of  liquid  will  at  once 
increase  the  viscosity,  diminish  the  velocity  of  the  renal  flow,  and 
tend  to  lessen  diuresis. 

There  is,  then,  little  more  reason  to  assume  that  the  copious  flow 
of  urine  which  follows  the  absorption  of  a  large  quantity  of  water 
is  due  to  a  mere  process  of  filtration  than  there  is  to  believe  that 
filtration,  and  not  selective  secretion,  is  the  cause  of  the  gush  of 
saliva  which  precedes  vomiting,  or  the  sudden  outburst  of  sweat  on 
sudden  and  severe  exertion.  In  addition,  there  are  the  positive 
proofs  already  mentioned  that  the  '  rodded  '  epithelium  of  the 
tubules,  which  no  one  supposes  to  be  abandoned  more  to  mere 
physical  influences  than  the  epithelium  of  the  salivary  glands,  plays 
a  part  in  the  secretion  of  some  of  the  urinary  constituents. 

As  to  the  nature  of  the  mechanism  set  in  motion,  and  the  series 
of  events  that  take  place  as  the  constituents  of  the  urine  journey 
from  the  interior  of  the  bloodvessels  to  the  lumen  of  the  tubules, 
we  know  no  more  than  in  the  case  of  other  glands.  This  alone  is 
clear,  that  the  separation  of  the  urine  from  the  blood  implies  the 
performance  of  a  large  amount  of  work  by  the  kidney.  For  the 
osmotic  pressure  of  urine  is  several  times  as  great  as  that  of  the 
plasma  of  the  blood.  Blood-plasma  freezes  at  —0-55°  to  —0-65°  C. 
(on  the  average,  say,  —  o-6°  C).  The  osmotic  pressure  correspond- 
ing to  —0-6°  C.  is  5,662  millimetres  of  mercury  (p.  422),  or,  in  round 
numbers,  75  metres  of  water.  Human  urine  has  been  found  to 
freeze  at  —1-38°  to  —2-11°  C.  (say,  on  the  average,  — 1-8°  C),  and 
for  highly  concentrated  urines  the  depression  of  the  freezing-point 
may  be  considerably  greater.  The  osmotic  pressure  corresponding 
to  — 1-8°  C.  is  i6,g86  millimetres  of  mercury  or  225  metres  of  water. 
This  exceeds  the  osmotic  pressure  of  the  plasma  by  150  metres  of 
water.  In  separating  a  kilogramme  of  urine  from  the  blood  the 
kidney  accordingly  does  work  approximately  equivalent  to  raising 
a  weight  of  a  kilogramme  to  the  height  of  150  metres — i.e.,  150  kilo- 
gramme-metres. It  is  evident  that  the  excess  of  the  blood-pressure 
in  the  glomeruli  over  the  pressure  of  the  urine  in  the  tubules,  which, 
even  if  we  neglect  the  latter  altogether — since  there  is  only  slight 
resistance  to  the  flow  of  urine  towards  the  bladder — cannot  at  most 
be  greater  than  100  millimetres  of  mercury,  or  1-35  metres  of  water, 
wnll  account  for  only  an  insignificant  part  of  this  work.  The  rest 
must  be  done  at  the  expense  of  the  energy  of  the  food  materials 
taken  up  by,  and  transformed  in,  the  cells  concerned  with  the  secre- 
tion of  the  urine.  But  we  do  not  know  in  what  way  these  cells, 
by  applying  this  energy,  perform  the  remarkable  feat  of  perma- 
nently maintaining  a  difference  of  fifteen  atmospheres  in  the  osmotic 

32 


498  EXCRETION 

pressure  of  the  liquids  in  contact  with  their  attached  and  free  sur- 
faces. A  token  of  the  intensity  of  the  metabohc  effort  required  is 
the  marked  increase  in  the  absorption  of  oxygen  which  occurs 
during  diuresis,  although  it  is  not  in  proportion  to  the  amount  of 
the  diuresis.  In  one  experiment  the  oxygen  absorbed  by  a  dog's 
kidneys  was  ii  per  cent,  of  what  would  have  been  used  up  by  the 
entire  animal  under  normal  conditions.  There  is  no  definite  relation 
between  the  oxygen  taken  in  and  the  carbon  dioxide  given  out  at 
any  moment. 

What  is  the  significance  of  the  peculiar  arrangement  of  the  glomerular 
bloodvessels,  if  the  epithelium  of  the  capsules  has  secretive  powers  like 
that  of  ordinary  glands  ?  It  is  difficult  to  believe  that  these  unique 
vascular  tufts  have  not  a  near  and  important  relation  to  the  renal 
function ;  but  it  is  by  no  means  clear  what  that  relation  is.  The  secretion 
of  water,  and  even  its  rapid  secretion,  is  not  at  all  bound  up  with  any 
set  arrangement  of  bloodvessels.  Gland-cells  all  over  the  body  secrete 
water  under  the  most  varied  conditions  of  blood -pressure,  although  a 
comparatively  high  pressure  is  upon  the  whole  favourable  to  a  copious 
outflow. 

But  the  kidney  has  other  functions  than  mere  excretion  (p.  649). 
And  it  may  be  that  the  simplest  part  of  the  latter  process,  the 
elimination  of  water  and  salts,  is  largely  thrown  upon  the  Malpighian 
corpuscles,  as  a  physiologically  cheaper  machine  than  the  epithelium 
of  the  tubules,  which  is  left  free  for  more  complex  labours.  These  may 
include  not  only  the  separation  of  nitrogenous  metabolites,  but  also 
synthetic  processes  possibly  concerned  in  the  regulation  of  protein 
metabolism.  One  characteristic  synthesis,  the  union  of  benzoic  acid 
and  glycin  to  hippuric  acid,  has  already  been  referred  to.  As  will  be 
shown  later  (p.  571),  it  takes  place  mainly,  in  some  animals  perhaps 
exclusively,  in  the  kidney.  The  epithelium  of  the  glomerulus,  being  a 
less  highly  organized  and  less  delicately  selective  mechanism  than  that 
of  the  convoluted  tubules,  may  more  easily  respond  to  increase  of  blood- 
pressure  by  increased  secretion.  At  the  same  time,  placed  as  it  is  at 
the  last  flood-gate  of  the  circulation,  where  the  escape  of  anything 
valuable  means  its  total  loss,  the  glomerular  epithelium  may  be  endowed 
with  a  general  power  of  resistance  to  transudation,  which  renders  a 
comparatively  high  blood-pressure  a  necessary  condition  of  its  acting 
at  all.  And  as  a  matter  of  fact  water  ceases  to  be  secreted  by  the 
kidney  long  before  the  blood-pressure  in  the  glomeruli  can  have  fallen 
below  that  which  suffices  for  the  highest  activity  of  the  liver.  Perhaps, 
however,  the  high  minimum  pressure  requii^ed  (30  to  40  mm.  of  mercury 
in  the  dog)  is  merely  the  necessary  consequence  of  the  long  and  difficult 
path  which  most  of  the  blood  going  through  the  kidney  has  to  take,  and, 
that  a  sufficient  blood-flow  cannot  be  kept  up  with  less.  It  may  be, 
too,  that  the  comparatively  small  surface  of  the  glomeruli,  restricted 
in  order  to  leave  room  for  the  more  highly  organized  parts  of  the  renal 
mechanism,  entails  the  more  intense  and  concentrated  activity  which 
the  high  blood-pressure  renders  possible,  and  the  simplicity  of  work 
and  organization  renders  harmless. 

An  obvious  result,  and  perhaps  an  important  one,  of  the  peculiar 
arrangement  of  the  bloodvessels  of  the  kidney  is  that  the  renal  tubules 
proper  are  shielded  from  an  excessive  blood-pressure  by  the  inter- 
position of  the  glomeruli  as  a  block.  This  may  be  either  because  the 
epithelium  of  the  tubules  would  not  perform  its  work  so  well  under  a 


THE  SECRETION  OF  THE  URINE  499 

high  blood-prcssurc,  or  because  there  would  be  a  danger  of  substances 
which  ought  to  be  retained  being  cast  out  into  the  urine.  In  this  con- 
nection it  is  interesting  to  note  that  the  specific  constituents  of  urine 
are  separated  by  cpithehum  surrounded  by  capillaries  of  the  second 
order,  and  therefore  with  a  smaller  blood-pressure  than  exists  in  the 
capillaries  of  most  glands,  while  the  same  is  true  of  bile,  another 
(practically)  protein -free  secretion. 

The  maximum  secretory  pressure  in  the  kidney,  as  shown  by  a 
manometer  tied  into  the  divided  ureter,  is  about  60  mm.  of  mercury 
in  the  dog,  or  less  than  half  that  of  saliva.  If  the  escape  of  the 
urine  is  opposed  by  a  greater  pressure  than  this,  or  if  the  ureter  is 
tied,  the  kidney  becomes  oedematous.  Whether  the  oedema  is  due 
to  reabsorption  of  urine  or  to  the  pouring  out  of  lymph  owing  to 
the  pressure  of  the  dilated  tubules  on  the  veins  has  not  been  de- 
finitely settled.  It  has  been  already  pointed  out  that  there  is  no 
necessary  relation  between  the  blood-pressure  in  the  capillaries  of 
a  gland  and  its  secretory  pressure;  and,  so  far  as  this  goes,  water 
might  just  as  well  be  secreted  at  a  pressure  of  60  mm.  of  mercury 
from  the  low-pressure  blood  of  the  second  set  of  renal  capillaries 
as  from  the  high-pressure  blood  of  the  glomeruli.  By  obstruction 
the  molecular  concentration  of  the  urine  is  diminished  to  half  or 
three-quarters  of  the  normal. 

The  Influence  of  the  Circulation  on  the  Secretion  of  Urine. — 
Although  the  activity  of  no  organ  in  the  body  is  governed  more 
by  the  indirect  effects  of  nervous  action  than  that  of  the  kidney, 
no  proof  has  been  given  of  the  existence  of  secretory  fibres  for  it 
comparable  to  those  of  the  salivary  glands.  All  the  changes  in  the 
rate  of  renal  secretion  which  follow  the  section  or  stimulation  of 
nerves  can  be  explained  as  the  consequences  of  the  rise  or  fall  of 
local  or  general  blood-pressure,  and  of  the  corresponding  variations 
in  the  velocity  of  the  blood  in  the  renal  vessels. 

The  best  way  to  study  variations  in  the  calibre  of  the  renal  vessels  is 
the  plethysmo graphic  method,  and  the  oncometer  of  Roy  is  a  pkthysmo- 
graph  adapted  to  the  kidney  (Fig.  192).  It  consists  of  a  metal  capsule 
lined  with  loose  membrane,  between  which  and  the  metal  there  is  a 
space  filled  with  oil.  The  two  halves  of  the  capsule  open  and  shut  on  a 
hinge;  and  the  kidney,  when  introduced  into  it,  is  surrounded  on  all 
sides  by  the  membrane,  the  vessels  and  ureter  passing  out  through  an 
opening.  The  oil-space  is  connected  with  a  cylinder  also  filled  with  oil, 
above  which  a  piston,  attached  to  a  lever,  moves.  The  lever  registers 
on  a  drum  the  changes  in  the  volume  of  the  kidney — i.e.,  practically  the 
changes  in  the  quantity  of  blood  in  it,  and  therefore  in  the  calibre  of 
its  vessels.  A  still  better  oncometer  is  that  of  Schiifer,  in  which  air  is 
employed  instead  of  oil. 

Nerves  of  the  Kidney. — Both  vaso-constrictor  and  vaso-dilator  fibres 
for  the  renal  vessels,  but  most  clearly  the  former,  have  been  shown 
to  leave  the  cord  (in  the  dog)  by  the  anterior  roots  of  the  sixth  thoracic 
to  second  lumbar  nerves,  and  especially  of  the  last  three  thoracic. 
They  run  in  the  splanchnics,  and  then  through  the  renal  plexus — around 
the  renal  artery — into  the  kidney.     The  vaso-constrictors  predominate, 


500 


EXCRETION 


so  that  the  general  efiect  of  stimulation  of  the  nerve-roots,  the  splanch- 
nics,  or  the  renal  nerves  is  shrinking  of  the  kidney,  with  diminution  or 
cessation  of  the  secretion  of  urine.  But  slow  rhythmical  stimulation 
of  the  roots  causes  increase  of  volume,  the  scanty  dilators  being  by  this 
method  excited  in  preference  to  the  constrictors. 

The  renal  nerves,  entering  at  the  hilum,  branch  repeatedly,  so  as  to 
form  a  wide-meshed  plexus  around  the  arteries,  and  accompany  them 
even  to  their  finest  ramifications  in  the  cortex.  Coming  off  from  the 
nerves  surrounding  the  arteries  are  fine  fibres  which  are  distributed  to 
the  convoluted  tubules.  Some  of  them  terminate  in  globular  ends, 
others  in  fine  threads  that  pass  through  the  membrana  propria  (Berkeley) . 

Section  of  the  renal  nerves  is  followed  by  relaxation  of  the  small 
arteries  in  the  kidney,  and  consequent  swelling  of  the  organ.  The 
flow  of  urine  is  greatly  increased,  and  sometimes  albumin  appears 
in  it,  the  excessive  pressure  in  the  capillaries  (particularly  in  those 

of  the  glomeruli)  being 
supposed  to  favour  the 
escape  of  substances  to 
which  a  passage  is  refused 
under  normal  conditions. 
An  experiment  which  is 
sometimes  quoted  as  a  de- 
cisive test  of  the  relative 
importance  of  changes  in 
the  rate  of  flow,  and  in 
the  pressure  of  the  blood 
within  the  glomeruli,  is 
that  of  tying  the  renal 
vein.  This  undoubtedly 
does  not  lower  the  intra- 
glomerular  pressure  —  on 
the  contrary,  it  must  in- 
crease it — but  the  secretion  of  urine  stops.  If  the  venous  outflow 
from  the  kidney  is  only  partially  interfered  with,  the  flow  of  urine  is 
immediately  diminished,  but  the  administration  of  a  diuretic  like 
potassium  nitrate  causes  an  increase.  It  is  more  than  likely  that 
in  these  experiments  the  secretion  stops  or  slackens  not  because  a 
high  blood-pressure,  but  because  an  active  circulation  is  its  necessary 
condition.  When  the  blood  stagnates  in  the  kidney  the  natural 
stimulus  to  the  renal  apparatus  speedily  disappears  owing  to  the 
elimination  of  the  urinary  constituents  to  the  neutral  or  indifferent 
point  (p.  496).  The  experiment,  however,  is  not  perfectly  conclu- 
sive. For  few  glands  can  go  on  performing  their  function  after  the 
circulation  has  ceased.  The  kidney  must  be  able  to  feed  itself  in 
order  to  continue  its  work.  Above  all,  it  needs  oxygen;  and  it 
might  be  urged  that  if  the  blood  in  the  glomeruli  could  be  kept  at 
the  normal  standard  of  arterial  blood,  secretion  might  still  go  on 
after  ligation  of  the  renal  vein. 


Fig.  192. — Diagram  oi  Organ-Plethysmograph  or 
Oncometer.  B,  metal  box  in  two  halves  open- 
ing on  the  hinge  H ;  M,  thin  membrane ;  A,  space 
filled  with  oil;  O,  organ  enclosed  in  oncometer; 
V,  vessels  of  organ;  /,  tube  for  filling  instrument 
with  oil;  T,  tube  connected  with  D,  which  opens 
into  cylinder  C;  C  is  also  filled  with  oil;  P,  pis- 
ton attached  by  E  to  a  writing  lever. 


THE  SECRETION  OF  THE  URINE  501 

According  to  Ludwig,  indeed,  the  flow  of  urine  stops,  in  spite 
of  continued  filtration  through  the  glomeruli,  because  the  swelling 
of  the  veins  in  the  boundary  layer  compresses  the  tubules,  and  may 
even  obliterate  their  lumen.  There  is  no  conclusive  experimental 
evidence,  however,  and  no  a  priori  probability,  that  the  obstruction 
so  produced  is  sufficiently  sudden  or  sufficiently  complete  to  cause 
instant  and  total  cessation  of  the  flow.  It  is  even  less  justifiable 
to  conclude  from  the  experiment  that  the  liquid  part  of  the  urine 
is,  at  any  rate,  not  separated  by  the  epithelium  of  the  tubules,  since 
the  blood-pressure  in  the  capillaries  around  the  tubules  must  rise 
very  greatly  after  ligature  of  the  vein,  and  yet  secretion  is  stopped. 
It  might  equally  well  be  argued  that  the  renal  epithelium  normally 
secretes  water  under  a  low  blood-pressure,  but  is  disorganized  under 
the  excessive  and  entirely  unaccustomed  pressure  which  follows  the 
closure  of  the  vein. 

It  is  not  only  through  nerves  directly  governing  the  calibre  of  the 
■  vessels  of  the  kidney  that  the  rate  of  urinary  secretion  can  be 
affected.  Any  change  in  the  general  blood-pressure,  if  not  counter- 
acted by,  still  more  if  conspiring  with,  simultaneous  local  changes 
in  the  renal  vessels,  may  be  followed  by  an  increased  or  diminished 
flow  of  urine ;  and  the  law  which  explains  all  such  variations,  or  at 
least  serves  to  sum  them  up,  is  that  in  general  an  increase  in  the 
rate  of  the  blood-flow  through  the  kidney  is  followed  by  an  increase  in 
the  rate  of  secretion.  It  will  be  remarked  that  this  is  the  converse 
of  the  great  law,  of  which  we  have  already  seen  so  many  illustra- 
tions, that  functional  activity  increases  blood-flow.  It  is  probable 
that  this  law  holds  for  the  kidney  as  well  as  for  other  organs,  but 
that  the  influence  of  activity  on  blood-supply  is  subordinated  to 
that  of  blood-supply  on  activity,  while  in  most  tissues,  as  in  the 
muscles,  the  opposite  is  the  case.  It  is  evident  that  an  increase  in 
the  blood- flow  would  favour  the  secretory  activity  of  the  renal  cells, 
since  the  average  concentration  of  the  blood  presented  to  them  as 
regards  those  constituents  which  they  select  would  remain  relatively 
high  in  its  circuit  through  the  kidney.  The  '  stimulus  '  to  secretion 
would,  therefore,  be  relatively  intense. 

Destruction  of  the  medulla  oblongata  {i.e.,  of  the  vaso-motor 
centre),  or  section  of  the  cord  below  it,  diminishes  the  secretion  of 
urine,  because  the  arterial  pressure  is  lowered  so  much  as  to  over- 
compensate  the  dilatation  of  the  renal  vessels,  which  the  operation 
also  brings  about.  If  the  blood-pressure  falls  below  40  mm.  of 
mercury,  the  secretion  is  abolished.  Stimulation  of  the  medulla  or 
cord  also  lessens  the  flow  of  urine  by  constricting  the  arterioles  of 
the  kidney  so  much  as  to  over-compensate  the  rise  of  general  blood- 
pressure,  caused  by  the  constriction  of  small  vessels  throughout  the 
body. 

If  the  renal  nerves  have  been  cut,  stimulation  of  the  medulla 


502  EXCRETION 

oblongata  increases  the  urinary  secretion,  because  now  the  rise  of 
general  blood-pressure  is  no  longer  counterbalanced  by  constriction 
of  the  renal  vessels.  An  increase  in  the  urinary  flow  can  be  pro- 
duced in  the  rabbit  by  a  lesion  in  a  part  of  the  funiculi  teretes, 
which  can  be  reached  in  the  floor  of  the  fourth  ventricle  (Eckhard), 
perhaps  by  destropng  the  portion  of  the  vaso-motor  centre  govern- 
ing the  renal  nerves,  while  the  rest  remains  uninjured,  or  is  even 
stimulated,  and  thus  keeps  up  or  even  increases  the  general 
blood-pressure.  There  is  either  no  glycosuria,  or  it  is  very 
slight. 

Section  of  the  splanchnic  nerves  causes  a  fall  of  arterial  pressure, 
which  is,  however  (in  animals  like  the  dog,  in  which  compensation 
soon  takes  place),  more  than  balanced  by  the  simultaneous  dilata- 
tion of  the  renal  vessels,  and  therefore  for  some  time  the  flow  of 
urine  is  increased,  but  not  so  much  as  when  the  renal  nerves  alone 
are  cut.  In  the  rabbit  there  is  no  increase.  On  the  other  hand, 
stimulation  of  the  splanchnics  stops  the  urinary  secretion,  because 
the  general  rise  of  pressure  is  not  enough  to  make  up  for  the  con- 
striction of  the  renal  vessels. 

Diuretics  are  substances  that  increase  the  flow  of  urine.  Some  of 
them  act  mainly  on  the  circulation,  as  by  increasing  the  general  blood- 
pressure,  others  mainly  by  a  direct  influence  on  the  secreting  mechanism. 
Digitalis  is  a  representative  of  the  first  class;  urea  and  caffein  belong  to 
the  second.  The  action  of  digitalis  is  to  strengthen  the  beat  of  the 
heart,  which  is  at  the  same  time  some,what  slowed,  and  to  constrict  the 
arterioles.  Both  effects  contribute  to  the  increase  of  pressure.  But 
the  accompanying  diuresis  is  due  to  the  cardiac  factor,  the  vaso-con- 
striction  which  involves  the  renal  vessels  also,  being  over-compensated. 
The  diuretic  effect  of  digitalis  is  much  greater  in  cardiac  disease  with 
dropsical  effusions  than  in  health.  Caffein,  when  injected  into  the 
blood,  affects  the  pressure  but  little.  It  causes  dilatation  of  the  renal 
vessels  after  a  passing  constriction,  and  an  increase  in  the  flow  of  urine 
after  a  temporary  diminution.  The  vascular  dilatation  is  not  the 
chief  reason  for  the  diuretic  effect,  for  the  latter  is  still  obtained  when  the 
vaso-motor  mechanism  has  been  paralyzed  by  chloral  hydrate,  and 
even  after  the  secretion  of  urine  has  been  stopped  by  the  fall  of  pressure 
consequent  on  section  of  the  spinal  cord.  Caffein,  therefore,  acts 
directly  on  the  renal  epithelium.  The  action  of  urea,  potassium 
nitrate,  and  the  saline  diuretics  is  probably  also  a  direct  action  on  the 
secreting  structures,  although  some  have  supposed  that  their  primary 
effect  is  to  cause  vaso-dilatation  in  the  kidney,  and  a  consequent  local 
increase  in  the  capillary  pressure. 

Summary. — Our  knowledge  of  renal  secretion  may  be  thus 
summed  up:  The  water  and  salts  of  the  urine  are  chiefly  separated 
by  the  glomeruli ;  the  process  is  not  a  mere  physical  filtration,  hut 
a  true  secretion.  Substances  like  sugar,  peptone,  egg-albumin,  and 
hcemoglobin,  when  injected  into  the  blood,  are  probably  excreted  mainly 
by  the  glomeruli ;  and  so  is  the  sugar  of  diabetes.  Urea,  uric  acid, 
and  presumably  the  other  organic  constituents  of  normal  urine,  ze>ith 


EXPULSION  OF  THE  URINE  503 

a  portion  of  the  ivater  and  salts,  are  excreted  by  the  physiological 
activity  of  the  '  rodded  '  epithelium  of  the  renal  tuhides.  The  rate  of 
secretion  of  urine  rises  and  falls  with  the  pressure,  and  still  more  with 
the  velocity,  of  the  blood  in,  the  renal  vessels.  No  secretory  nerves  for 
the  kidney  have  been  found ;  the  effects  of  section  or  stimulation  of 
nerves  on  the  secretion  can  all  he  explained  by  the  changes  produced  in 
the  renal  blood-flow.  Some  diuretics  act  by  increasing  the  blood-flow, 
others  directly  on  the  epithelium  of  the  tubules  or  the  glomeruli. 

Section  III. — Expulsion  of  the  Urine. 

Micturition. — ^The  urine,  like  the  bile,  is  being  constantly  formed; 
although  secretion  varies  in  its  rate  from  time  to  time,  it  never 
ceases.  Trickling  along  the  collecting  tubules,  the  urine  reaches 
the  pelvis  of  the  kidney,  from  which  it  is  propelled  along  the  ureters 
by  peristaltic  contractions  of  their  walls,  and  drops  from  their  valve- 
like orifices  into  the  bladder.  When  this  becomes  distended,  rhyth- 
mical peristaltic  contractions  are  set  up  in  it,  and  notice  is  given 
of  its  condition  by  a  characteristic  sensation,  which  is  perhaps  aided 
by  the  squeezing  of  a  few  drops  of  urine  past  the  tonically  con- 
tracted circular  fibres  that  form  a  sphincter  round  the  neck  of  the 
bladder,  and  into  the  first  part  of  the  urethra.  The  desire  to  empty 
the  bladder  can  be  resisted  for  a  time,  as  can  the  desire  to  empty 
the  bowel.  If  it  is  yielded  to,  the  smooth  muscular  fibres  in  the 
wall  of  the  viscus  are  thrown  into  contraction.  This  is  aided  by  an 
expulsive  effort  of  the  abdominal  muscles.  The  sphincter  vesicae 
is  relaxed;  and  the  urine  is  forced  along  the  urethra,  its  passage 
being  facilitated  by  discontinuous  contractions  of  the  ejaculator 
urinse  muscle,  which  also  serve  to  squeeze  the  last  drops  of  urine 
from  the  urethral  canal  at  the  completion  of  the  act. 

Regurgitation  into  the  ureters  is  to  a  great  extent  prevented  by 
their  compression  between  the  mucous  and  muscular  coats  of  the 
bladder,  where  they  run  for  more  than  half  an  inch  before  opening 
at  the  posterior  angle  of  the  trigone.  But  it  has  been  shown  that 
a  certain  amount  of  back  flow  can  take  place.  Small  bodies  like 
diatoms  suspended  in  water  and  pigments  dissolved  in  it  have  been 
found  in  the  pelvis  of  the  kidney,  the  renal  tubules,  and  even  the 
circulation  after  being  injected  into  the  bladder. 

The  pressure  in  the  bladder  of  a  man  may  be  made  as  high  as 
10  cm.  of  mercury  during  the  act  of  micturition;  about  half  this 
amount  is  due  to  the  contraction  of  the  vesical  walls  alone,  the 
rest  to  the  contraction  of  the  abdominal  muscles.  A  pressure  of 
16  to  26  mm.  of  mercury  is  required  to  open  the  sphincter  of  a 
rabbit's  bladder  in  life. 

Although  the  whole  performance  seems  to  us  to  be  completely 
voluntary,  there  are  facts  which  show  that  it  is  at  bottom  a  reflex 


504  EXCRETION 

series  of  co-ordinated  movements,  that  can  be  started  by  impulses 
passing  to  a  centre  in  the  spinal  cord  from  above  or  from  below — 
from  the  brain  or  from  the  bladder.  In  dogs,  with  the  spinal  cord 
divided  at  the  upper  level  of  the  lumbar  region,  micturition  takes 
place  regularly  when  the  bladder  is  full,  and  can  be  excited  by  such 
slight  stimuli  as  sponging  of  the  skin  around  the  anus  (Goltz). 
Here,  of  course,  the  act  is  entirely  reflex;  and  the  centre  is  situated 
at  the  level  of  the  fifth  lumbar  nerves.  The  efferent  nerves  of  the 
bladder,  like  those  of  the  rectum,  come  partly  from  the  cord  directly 
through  the  sacral  nerves,  and  partly  through  the  lumbar  sympa- 
thetic chain  (second  to  sixth  ganglia).  The  sacral  fibres  are  con- 
nected with  nerve  cells  in  the  hypogastric  plexus,  and  the  sympa- 
thetic, partly  at  least,  in  the  inferior  mesenteric  ganglia.  This 
anatomical  coincidence  acquires  interest  in  view  of  the  striking 
physiological  similarity  between  the  processes  of  micturition  and 
defcecation,  a  similarity  which  is  emphasized  by  the  fact  that  the 
latter  is  almost  invariably  accompanied  by  the  former.  An  im- 
portant difference,  however,  is  that  the  will  can  far  more  readily 
set  in  motion  the  machinery  of  micturition  than  that  of  defaecation ; 
a  man  can  generally  empty  his  bladder  when  he  likes,  but  he  cannot 
empty  his  bowels  when  he  likes. 

Sometimes  in  disease,  and  especially  in  disease  of  the  spinal  cord, 
the  mechanism  of  micturition  breaks  down;  the  bladder  is  no 
longer  emptied;  it  remains  distended  with  urine,  which  dribbles 
away  through  the  urethra  as  fast  as  it  escapes  from  the  ureters. 
To  this  condition  the  term  incontinence  of  urine  is  properly 
applied. 

Reflex  emptying  of  the  bladder,  without  an  act  of  will  or  during 
unconsciousness,  is  not  true  incontinence.  The  involuntary  mic- 
turition of  children  during  sleep,  for  example,  is  a  perfectly  normal 
reflex  act,  although  more  easily  excited  and  less  easily  controlled 
than  in  adults.  Section  either  of  both  nervi  erigentes,  or  of  both 
hypogastrics,  is  never  followed  by  more  than  quite  temporary  dis- 
turbance of  function  of  the  bladder  in  dogs,  both  male  and  female. 
In  a  few  days  the  urine  is  normally  passed.  In  bitches  the  same 
is  true  when  both  pairs  of  nerves  are  divided.  But  in  male  dogs 
true  incontinence  of  urine  follows  section  of  the  four  nerves,  as  well 
as  intense  tenesmus  due  to  paralysis  of  the  lower  part  of  the  large 
intestine. 

Section  IV. — Excretion  by  the  Skin. 

Besides  permitting  of  the  trifling  gaseous  interchange  already 
referred  to  (p.  292).  the  skin  plays  an  important  part  in  the  elimina- 
tion of  water  by  the  sweat-glands. 

Sweat  is  a  clear  colourless  liquid  of  low  specific  gravity  (1003  to 
1006),  consisting  chiefly  of  water  with  small  quantities  of  salts, 


EXCRETION  BY  THE  SKIN  505 

neutral  fats,  volatile  fatty  acids,  and  the  merest  traces  of  proteins 
and  urea.  It  is  acid  to  litmus  except  in  profuse  sweating,  when  it 
may  become  neutral  or  even  alkaline.  It  is  secreted  by  simple 
gland-tubes,  which  form  coils  lined  with  a  single  layer  of  columnar 
epithelium,  in  the  subcutaneous  tissue,  with  long  ducts  running  up 
to  the  surface  through  the  true  skin  and  epidermis.  Unless  col- 
lected from  the  parts  of  the  skin  on  which  there  are  no  hairs,  such 
as  the  palm,  it  is  apt  to  be  m.xed  with  sebum,  a  secretion  formed 
by  the  breaking  down  of  the  cells  of  the  sebaceous  glands,  which 
open  into  the  hair  follicles,  and  consisting  chiefly  of  glycerin  and 
cholesterin  fats,  soaps,  and  salts.  Sebum  is  probably  of  consider- 
able importance  for  maintaining  the  normal  condition  of  the  hair 
and  skin. 

Although  it  is  only  occasionally  that  sweat  collects  in  visible 
amount  on  the  skin,  water  is  always  being  given  off  in  the  form  of 
vapour.  This  invisible  perspiration  leaves  behind  it  on  the  skin, 
or  in  the  glands,  the  whole  of  the  non-volatile  constituents,  which 
may  be  to  some  extent  reabsorbed ;  and  since  even  the  visible  per- 
spiration is  in  large  part  evaporated  from  the  very  mouths  of  the 
glands  in  which  it  is  formed,  the  sweat  can  hardly  be  considered  a 
vehicle  of  solid  excretion,  even  to  the  small  extent  indicated  by  its 
chemical  composition. 

The  total  quantity  of  water  excreted  by  the  skin,  and  the  relative 
proportions  of  visible  and  invisible  perspiration,  vary  greatly.  A 
dry  and  warm  atmosphere  increases,  and  a  moist  and  cold  atmo- 
sphere diminishes  the  total,  and,  within  limits,  the  invisible  per- 
spiration. Visible  sweat — given  the  condition  of  rapid  heat-produc- 
tion in  the  body  as  in  muscular  labour — is  more  readily  deposited 
on  freely  exposed  surfaces  when  the  air  is  moist  than  when  it  is  dry. 
The  air  in  contact  with  surfaces  covered  by  clothing  is  never  far 
from  being  saturated  with  watery  vapour.  Here,  accordingly,  a 
comparatively  slight  increase  in  the  activity  of  the  sweat-glands 
suffices  to  produce  more  water  than  can  be  at  once  evaporated; 
and  the  excess  appears  as  sweat  on  the  skin,  to  be  absorbed  by 
the  clothing  without  evaporation,  or  to  be  evaporated  slowly,  as 
the  pressure  of  the  aqueous  vapour  gradually  diminishes  in  con- 
sequence of  diffusion.  The  power  of  imbibition  (p.  420)  of  water 
by  the  various  layers  of  the  skin  diminishes  as  we  pass  outwards, 
and  the  cells  of  the  epidermis  are  characterized  by  the  rapidity  with 
which  they  return  from  a  condition  of  excessive  imbibition  to  their 
normal  state.  This  constitutes  a  protective  mechanism  against 
excessive  loss  of  water.  When  the  skin  is  thoroughly  moistened,  its 
degree  of  imbibition  is  three  times  the  normal. 

The  quantity  of  siveat  given  off  by  a  man  in  twenty-four  hours 
varies  so  much  that  it  would  not  be  profitable  to  quote  here  the 
numerical  results  obtained  under  different  conditions  of  tempera- 


506  EXCRETION 

ture  and  humidity  of  the  air  (but  see  p.  666).  It  is  enough  to  say 
that  the  excretion  of  water  from  the  skin  is  of  the  same  order  of 
magnitude  as  that  from  the  kidneys:  a  man  loses  upon  the  whole 
as  much  water  in  sweat  as  in  urine.  But  it  is  to  be  carefully  noted 
that  these  two  channels  of  outflow  are  complementary  to  each 
other;  when  the  loss  of  water  by  the  skin  is  increased,  the  loss  by 
the  kidneys  is  diminished,  and  vice  versa. 

The  Influence  of  Nerves  on  the  Secretion  of  Sweat. — The  sweat- 
glands  are  governed  directly  by  the  nervous  system;  and  though 
an  actively  perspiring  skin  is,  in  health,  a  flushed  skin,  the  vascular 
dilatation  is  a  condition,  and  not  the  chief  cause  of  the  secretion. 
Stimulation  of  the  peripheral  end  of  the  sciatic  nerve  causes  a 
copious  secretion  of  sweat  on  the  pad  and  toes  of  the  corresponding 
foot  of  a  young  cat,  and  this  although  the  vessels  are  generally 
constricted  by  excitation  of  the  vasomotor  nerves.  Not  only  so, 
but  when  the  circulation  in  the  foot  is  entirely  cut  off  by  compres- 
sion of  the  crural  artery  or  by  amputation  of  the  limb,  stimulation 
of  the  sciatic  still  calls  forth  some  secretion.  As  in  the  case  of  the 
salivary  glands,  injection  of  atropine  abolishes  the  secretory  power 
of  the  sciatic,  while  leaving  its  vaso-motor  influence  untouched;  and 
pilocarpine  increases  the  flow  of  sweat  by  direct  stimulation  of  the 
endings  of  the  secretory  nerves  in  the  glands. 

That  the  sweating  caused  by  a  high  external  temperature  is 
normally  brought  about  by  nervous  influence,  and  not  by  direct 
action  on  the  secreting  cells,  is  shown  by  the  following  experiments. 
One  sciatic  nerve  is  divided  in  a  cat,  and  the  animal  put  into  a  hot- 
air  chamber.  No  sweat  appears  on  the  foot  whose  nerve  has  been 
cut,  but  the  other  feet  are  bathed  in  perspiration.  Similarly,  a 
venous  condition  of  the  blood  (in  asphyxia)  causes  sweating  in  the 
feet  whose  nerves  have  not  been  divided,  but  none  in  the  other 
foot;  and  stimulation  of  the  central  end  of  the  cut  sciatic  has  the 
same  effect.  All  this  points  to  the  existence  of  a  reflex  mechanism ; 
and  it  is  certain  that  asphyxia  acts  by  direct  stimulation  of  the 
centre  or  centres.  The  vaso-motor  centre  is  at  the  same  time 
stimulated,  and  the  bloodvessels  constricted,  as  in  the  cold  sweat 
of  the  death  agony.  Fear  may  also  cause  a  cold  sweat,  impulses 
passing  from  the  cerebral  cortex  to  the  vaso-motor  and  sweat 
centres. 

It  is  probable  that  a  general  sweat  -  centre  exists  in  the  medulla 
oblongata,  but  its  position  has  not  been  exactly  determined  nor  even 
its  existence  definitely  proved.  On  the  other  hand,  it  is  known  that 
in  the  cat  there  are  at  least  two  spinal  centres,  one  for  the  fore-limbs 
in  the  lower  part  of  the  cervical  cord,  and  another  for  the  hind-limbs 
where  the  dorsal  portion  of  the  cord  passes  into  the  lumbar.  That  this 
latter  centre  does  not  exist  or  is  comparatively  inactive  in  man  is 
indicated  by  the  following  case :  A  man  fell  from  a  window  and  fractured 
his  backbone  at  the  fifth  dorsal  vertebra.  The  lower  half  of  the  body 
was  paralyzed  for  a  time,  but  recovered.     Ultimately,  however,  the 


EXCRETION  BY  THE  SKIN  507 

paralysis  returned ;  and  shortly  before  his  death  (twenty-one  years  after 
the  accident)  it  was  noticed  that  a  copious  perspiration  broke  out 
several  times  on  the  upper  part  of  the  body,  while  the  lower  portion 
remained  perfectly  dry.  If  there  is  any  fimctional  spinal  centre  in  man, 
it  appears  to  lie  above  the  fifth  spinal  segment.  For  it  was  seen  in  a 
professional  diver  who  fractured  his  neck  at  that  level,  and  lived  three 
montlis  after  the  accident,  that  sweat  frequently  appeared  on  parts  of 
the  body  above  the  lesion,  but  never  below.  At  the  autopsy  the  whole 
thickness  of  the  cord,  except  perhaps  a  small  portion  of  the  anterior 
columns,  was  found  destroyed.  Of  course,  it  may  be  that  in  man  the 
spinal  centres,  although  normally  active,  lose  their  function  for  a  long 
time  after  such  severe  injuries  to  the  cord,  owing  to  the  condition  known 
as  shock. 

The  secretory  fibres  for  the  fore-limbs  (in  the  cat)  leave  the  cord  in 
the  anterior  roots  of  the  fourth  to  ninth  thoracic  nerves.  They  pass  by 
white  rami  communicantes  to  the  sympathetic  chain,  in  which  they 
reach  the  ganglion  stellatum,  where  they  are  all  connected  with  ner\'e- 
cells.  Then,  as  non-medullatcd  fibres,  they  gain  the  brachial  plexus 
by  the  grey  rami,  and  run  in  the  median  and  ulnar  to  the  pads  of  the 
feet.  The  fibres  for  the  hind-limbs  leave  the  cord  in  the  anterior  roots 
of  the  twelfth  thoracic  to  the  third  or  fourth  lumbar  nerves;  pass  by  the 
white  rami  to  the  sympathetic  ganglia,  in  which  they  form  connections 
with  ganglion  cells;  then,  as  non-medullated  fibres,  run  along  the  grey 
rami,  and  are  distributed  to  the  foot  in  the  sciatic. 

The  evidence  of  the  direct  secretory  action  of  nerves  on  the  sweat- 
glands  is  singularly  striking  and  complete,  in  contrast  to  what  we 
know  of  the  kidney.  In  the  latter,  blood-flov;  is  the  important 
factor;  increased  blood- flow  entails  increased  secretion.  In  the 
former,  the  nervous  impulse  to  secretion  is  the  spring  which  sets 
the  machinery  in  motion;  vascular  dilatation  aids  secretion,  but 
does  not  generally  cause  it.  It  would,  however,  be  easy  to  lay  too 
much  stress  on  this  distinction,  for  in  the  horse  the  mere  dilatation 
of  the  bloodvessels  of  the  head  after  section  of  the  cervical  sympa- 
thetic has  been  found  to  be  accompanied  by  increased  secretion  of 
sweat,  and  urinary  secretion  can  certainly  be  affected  by  the  direct 
action  of  various  substances  on  the  secretory  mechanism,  indepen- 
dently of  vascular  changes.  But  the  broad  difference  stands  out 
clearly  enough,  and  the  reason  of  it  lies  in  the  essentially  different 
purpose  of  the  two  secretions.  The  water  of  the  urine  is  in  the 
main  a  vehicle  for  the  removal  of  its  solids;  the  solids  of  the  sweat 
are  accidental  impurities,  so  to  speak,  in  the  water.  The  kidney 
eliminates  substances  which  it  is  vital  to  the  organism  to  get  rid 
of;  the  sweat-glands  pour  out  water,  not  because  it  is  in  itself 
hurtful,  not  because  it  cannot  pass  out  by  other  channels,  but 
because  the  evaporation  of  water  is  one  of  the  most  important 
means  by  which  the  temperature  of  the  body  is  controlled.  In 
short,  urine  is  a  true  excretion,  sweat  a  heat-regulating  secretion. 
No  hurtful  effects  are  produced  when  elimination  by  the  skin  is 
entirely  prevented  by  varnishing  it,  provided  that  the  increased 
loss  of  heat  is  compensated.     A  rabbit  with  a  varnished  skin  dies 


5o8 


EXCRETION 


of  cold,  as  a  rabbit  with  a  closely-clipped  or  shaven  skin  does; 
suppression  of  the  secretory  function  of  the  skin  has  nothing  to  do 
with  death  in  the  first  case  any  more  than  in  the  second  (p.  293). 


PRACTICAL  EXERCISES  ON  CHAPTER  IX. 

Urine, 

For  most  of  the  exp:riments  human  urine  is  employed — in  the 
quantitative  work  the  mixed  urine  of  the  twenty-four  hours.  Urine  may 
also  be  obtained  from  animals.  In  rabbits  pressure  on  the  abdomen 
will  usually  empty  the  bladder.  Dogs  may  be  taught  to  micturate  at 
a  set  time  or  place,  or  kept  in  a  cage  arranged  for  the  collection  of  urine. 
Or  a  catheter  may  be  used  (p.  690). 

I.  Specific  Gravity, — Pour  the  urine  into  a  glass  cylinder,  and  remove 
froth,  if  necessary,  with  filter-paper.     Place  a  urinometer  (Fig.   193) 
in  the  urine,  and  see  that  it  does  not  come  in  contact 
with  the  side  of  the  vessel.     Read  off  on  the  graduated 
ro  stem  the  division  which  corresponds  with  the  bottom 

o  of  the  meniscus.     This  gives  the  specific  gravity. 

,g  2.  Reaction. — (a)  Test  with  litmus-paper.    Generally 

^  the  litmus  is  reddened,  but  occasionally  in  health  the 

urine  first  passed  in  the  morning  is  alkaline.  Some- 
times urine  has  an  amphicroic  reaction — i.e.,  affects 
both  red  and  blue  litmus-paper.  This  is  the  case  when 
there  is  such  a  relation  between  the  bases  and  acids 
that  both  acid  and  '  neutral  '  (dibasic)  phosphates  are 
present  in  certain  proportions.  The  acid  phosphate 
reddens  blue  litmus,  and  the  '  neutral  '  phosphate 
turns  red  litmus  blue. 

(6)   Titratahle  Acidity. — To  25  c.c.  of  urine  add  15 
to  20  grammes  of  powdered  potassium  oxalate,  and 
one  or  two  drops  of  a  i  per  cent,  solution  of  phenol- 
phthalein.     Shake  the  mixture  rapidly  for  a  minute 
Fig.    193. — Urin-     or  two,  and  then  titrate  with  decinormal  sodium  hy- 
ometer.  droxide  at  once  (while  still  cold  from  the  solution  of  the 

oxalate)  till  a  faint  pink  colour  remains  permanent  on 
shaking.  The  potassium  oxalate  is  added  to  counteract  the  tendency 
of  the  calcium  present  in  urine  to  form  basic  phosphates,  which  would 
be  precipitated,  and  the  acidity  of  the  urine  thus  increased  (Folin). 

3.  Chlorides — (a)  Qualitative  Test. — Add  a  drop  of  nitric  acid  and  a 
drop  or  two  of  silver  nitrate  solution.  The  nitric  acid  is  added  to 
prevent  precipitation  of  silver  phosphate.  A  white  precipitate  soluble 
in  ammonia  shows  the  presence  of  chlorides.  The  precipitate  appears 
to  be  incompletely  soluble  in  ammonia,  since  the  ammonia  brings  down 
a  small  precipitate  of  earthy  phosphates. 

{b)  Quantitative  Estimation. — The  quantitative  estimation  of  the 
chlorine  in  urine  without  previous  evaporation  and  incineration  is  best 
made  by  one  of  the  modifications  of  Volhard's  method.  It  depends  upon 
the  complete  precipitation  of  the  chlorine  combined  with  the  alkaline 
metals,  and  also  of  sulphocyanic  acid,  by  silver  from  a  solution  con- 
taining nitric  acid  in  excess ;  and  avoids  the  error  introduced  into  simpler 
methods,  like  Mohr's,  by  the  union  of  some  of  the  silver  with  other 
substances  than  chlorine.     A  given  quantity  of  a  standard  solution  of 


PRACTICAL  EXERCISES  509 

silver  nitrate  (more  than  sufficient  to  combine  with  all  the  chlorine)  is 
added  to  a  given  volume  of  urine.  The  excess  of  silver  is  now  estimated 
by  means  of  a  standard  solution  of  ammonium  sulphocyanide,  which 
precipitates  the  silver  as  insoluble  silver  sulphocyanide.  A  fairly  strong 
solution  of  the  double  sulphate  of  iron  and  ammonium  (known  as  iron- 
ammonia-alum)  is  taken  as  the  indicator,  since  a  ferric  salt  does  not 
give  the  usual  red  colour  with  a  sulphocyanide  so  long  as  any  silver  in  the 
solution  is  uncombined  with  sulphocyanic  acid.  The  iron-ammonia- 
alum  forms  the  red  salt,  ferric  sulphocyanide,  when  any  excess  of 
ammonium  sulphocyanide  is  present,  but  it  does  not  react  with  silver 
sulphocyanide. 

The  standard  solution  of  silver  nitrate  can  be  made  by  dissolving 
29'o63  grammes  of  pure  fused  silver  nitrate  in  distilled  water  and  making 
up  the  volume  of  the  solution  accurately  to  i  litre.  The  solution  should 
be  kept  in  the  dark.  One  c.c.  of  this  solution  corresponds  to 
o-oi  gramme  NaCl  or  o '00607  gramme  CI. 

The  standard  solution  of  ammonium  sulphocyanide  is  prepared  as 
follows:  Dissolve  13  grammes  of  pure  ammonium  sulphoc^^anide 
(NH4CNS)  in  a  litre  of  distilled  water.  Measure  with  a  pipette  into 
a  beaker  20  c.c.  of  the  standard  silver  nitrate  solution,  and  add  5  c.c. 
of  the  iron  alum  solution  and  4  c.c.  of  pure  nitric  acid  (specific  gravity 
I '2).  Fill  a  burette  with  the  sulphocyanide  solution,  and  run  it  into 
the  silver  nitrate  solution  until  a  faint  permanent  red  tinge  is  obtained. 
Note  the  number  of  c.c.  of  the  sulphocyanide  solution  required,  and 
then  dilute  the  solution  till  2  c.c.  of  the  sulphocyanide  solution  corre- 
spond exactly  to  i  c.c.  of  the  silver  solution,  so  as  just  to  allow  of  the 
end  reaction  with  the  iron  solution  being  seen,  and  no  more. 

To  carry  out  the  method,  put  10  c.c.  of  urine,  which  must  be  free 
from  albumin,  in  a  stoppered  flask,  with  a  mark  corresponding  to  100  c.c. 
or  a  graduated  cylinder.  Add  50  c.c.  of  water,  4  c.c.  of  pure  nitric  acid 
(specific  gravity  1-2),  and  15  c.c.  of  the  standard  silver  solution;  shake 
well,  fill  with  water  to  the  mark,  and  again  shake.  After  the  precipitate 
has  settled,  filter  it  off.  Take  50  c.c.  of  the  filtrate,  add  5  c.c.  of  the 
solution  of  iron-ammonia-alum,  and  run  in  from  a  burette  the  standard 
solution  of  ammonium  sulphocyanide  until  a  weak  but  permanent  red 
coloration  appears. 

Suppose  X  c.c.  of  the  sulphocyanide  solution  are  required,  then  the 
chlorine  in  10  c.c.  of  urine  evidently  corresponds  to  (15  —  x),  o'oi  gramme 
NaCl 

4.  Phosphates — (i)  Qualitative  Tests. — [a)  Render  the  urine  alkaUne 
with  ammonia.  A  precipitate  of  earthy  phosphates  (calcium  and  mag- 
nesium phosphates)  falls  down.  Filter.  The  filtrate  contains  the 
alkaline  phosphates.  To  the  filtrate  add  magnesia  mixture.*  The 
alkaline  phosphates  (sodium,  potassium,  or  ammonium  phosphates) 
are  precipitated  as  ammonio-magnesic  or  triple  phosphate,  (b)  Add  to 
urine  half  its  volume  of  nitric  acid  and  a  little  molybdate  of  ammonium, 
and  heat.  A  yellow  precipitate  of  ammonium  phospho-molybdate 
shows  that  phosphates  are  present.  This  test  is  given  both  by  alkaline 
and  earthy  phosphates. 

(2)  Quantitative  Estimation. — The  quantitative  estimation  of  phos- 
phoric acid  in  urine  is  best  done  volumetrically,  by  titration  with  a 
standard  solution  of  uranium  nitrate,  using  ferrocyanide  of  potassium 
as  the  indicator.  Uranium  nitrate  gives  with  phosphates,  in  a  solution 
containing  free  acetic  acid,  a  precipitate  with  a  constant  proportion  of 

*  Magnesium  chloride  no  grammes,  ammonium  chloride  140  grammes, 
ammonia  (specific  gravity  0*91)  250  c.c,  and  water  1,750  c.c. 


510  EXCRETION 

phosphoric  acid.  As  soon  as  there  is  more  uranium  in  the  solution  than 
is  required  to  combine  with  all  the  phosphoric  acid,  a  brown  colour  is 
given  with  potassium  ferrocyanide,  due  to  the  formation  of  uranium 
ferrocyanide.  In  carrying  out  the  method,  5  c.c.  of  a  mixture  of  acetic 
acid  and  sodium  acetate  (there  are  10  grammes  of  sodium  acetate  and 
10  grammes  of  glacial  acetic  acid  in  100  c.c.  of  the  mixture)  are  added 
to  50  c.c.  of  urine,  which  is  then  heated  in  a  beaker  on  the  water-bath 
almost  to  boiling.  The  standard  uranium  solution  (which  contains 
35'5  grammes  of  uranium  nitrate  in  the  litre,  and  i  c.c.  of  which  corre- 
sponds to  0-005  gramme  P2O5)  is  now  run  in  from  a  burette,  until  a  drop 
of  the  urine  gives,  with  a  drop  of  potassium  ferrocyanide  solution,  on  a 
porcelain  slab,  a  brown  colour.  Uranium  acetate  may  be  used  instead 
of  uranium  nitrate,  but  the  latter  keeps  best.  When  uranium  acetate 
is  employed  it  is  not  necessary  to  add  the  sodium  acetate  mixture. 

5.  Sulphates — (i)  Qualitative  Test. — Add  to  urine  a  drop  of  hydro- 
chloric acid  and  then  a  few  drops  of  barium  chloride.  A  white  pre- 
cipitate comes  down,  showing  that  inorganic  sulphates  are  present. 
The  hydrochloric  acid  prevents  precipitation  of  the  phosphates. 

(2)  Quantitative  Estimation  of  the  Sulphates  (Inorganic  and  Ethereal). 
— Add  to  50  c.c.  of  albumin-free  urine  in  a  200-c.c.  Erlenmeyer  flask 
5  c.c.  of  a  4  per  cent,  potassium  chlorate  solution  and  5  c.c.  of  strong 
hydrochloric  acid,  and  boil  the  mixture  to  break  up  the  ethereal  sul- 
phates. In  five  to  ten  minutes  it  becomes  perfectly  colourless.  While 
it  continues  to  boil,  25  c.c.  of  a  10  per  cent,  solution  of  barium  chloride 
are  added  by  drops,  at  such  a  rate  that  it  takes  about  five  minutes  to 
add  this  quantity.  The  flask  is  now  put  on  the  water-bath  for  one-half 
to  one  hour,  till  the  precipitate  has  settled.  Then  filter  through  an 
ash-free  filter.  Wash  the  precipitate  on  the  filter  for  half  an  hour  with 
hot  water.  During  the  first  twenty  minutes  of  the  washing,  at  intervals 
of  a  few  minutes,  substitute  hot  5  per  cent,  ammonium  chloride  solution 
for  the  water.  At  the  end  of  the  half -hour's  washing,  as  soon  as  the 
water  has  run  through  the  filter,  fold  up  the  latter  and  press  it  gently 
between  dry  filter-papers  to  remove  a  portion  of  the  water.  Then  place 
the  filter  in  a  weighed  porcelain  crucible.  Pour  into  the  crucible  3  or  4 
c.c.  of  alcohol,  and  ignite  it,  to  dry  and  partially  bum  the  filter-paper. 
Then  incinerate  till  all  the  carbon  is  burned  off,  cool,  and  weigh.  From 
the  weight  of  the  barium  sulphate,  the  sulphuric  acid  in  50  c.c.  of  urine 
is  easily  calculated  (SO4  in  i  gramme  of  barium  sulphate,  0'4ii87 
gramme)  (Folin). 

(3)  Quantitative  Estimation  of  the  Sulphuric  Acid  united  with  Aromatic 
Bodies  [Aromatic  or  Ethereal  Sulphates) . — Put  200  c.c.  of  the  same  urine 
as  used  in  (2)  into  a  beaker.  Add  100  c.c.  of  10  per  cent,  barium 
chloride  solution  in  the  cold.  Let  stand  for  twenty-four  hours.  Then 
decant  off  the  clear  supernatant  liquid,  and  filter  it.  Measure  150  c.c. 
of  the  clear  filtrate,  corresponding  to  100  c.c.  of  the  urine,  into  a  400-c.c. 
Erlenmeyer  flask.  Add  10  or  15  c.c.  of  concentrated  hydrochloric  acid 
and  10  to  15  c.c.  of  4  per  cent,  potassium  chlorate.  Heat  the  mixture 
to  boiling,  and  proceed  as  in  (2).  From  the  weight  of  the  barium  sul- 
phate, the  ethereal  sulphuric  acid  in  100  c.c.  of  urine  can  be  calculated. 
Deducting  this  from  the  quantity  per  100  c.c.  of  urine  obtained  in  (2), 
we  get  the  amount  of  inorganic  sulphuric  acid  per  100  c.c.  (Folin). 

6.  Indoxyl  (contained  in  the  urine  as  indican,  the  potassium  salt  of 
indoxyl-sulphuric  acid)  can  be  oxidized  into  indigo,  and  so  detected 
and  estimated. 

A  qualitative  test  is  the  following:  Ten  c.c.  of  horse's  urine  is  mixed 
with  10  c.c.  of  Obermayer's  reagent  (pure  concentrated  hydrochloric 
acid  containing  2  to  4  parts  of  ferric  chloride  in  1,000),  and  shaken  well 


PRACTICAL  EXERCISES  511 

for  a  minute  or  two ;  a  bluish  colour  appears  if,  as  is  generally  the  case, 
indoxj-I  is  present,  indigo  (CigHjoNg'^a)  being  formed  by  the  oxidizing 
action  of  the  ferric  chloride  on  the  indoxjd,  the  compound  of  which 
with  sulphuric  acid  has  been  broken  up  by  the  hydrochloric  acid.  The 
urine  must  be  free  from  albumin.  In  performing  the  test  in  human 
urine,  which  contains  a  smaller  quantity  of  the  indigo-forming  sub- 
stance, the  faint  blue  liquid  should  be  shaken  up  with  a  few  drops  of 
chloroform.  The  latter  takes  up  the  colour,  which  is  thus  rendered 
more  evident.  If  there  is  difficulty  in  obtaining  the  reaction,  the  urine 
may  first  be  decolorized  by  precipitating  it  with  acetate  of  lead, 
avoiding  excess.  The  precipitate  is  filtered  off,  and  the  test  then 
applied  to  the  clear  filtrate.  The  skatoxyl  of  urine  can  also  be  oxidized 
to  indigo,  but  it  is  present  in  far  smaller  amount.  The  average  quantity 
of  indigo  obtained  from  a  litre  of  horse's  urine  is  about  150  milligrammes ; 
from  a  litre  of  human  urine,  not  a  twentieth  of  that  amount. 

For  comparative  quantitative  determinations  the  method  of  Folin 
may  be  used.  One-hundredth  of  the  twenty-four  hours'  urine  is  taken. 
In  this  the  indigo  is  developed  by  the  addition  of  an  equal  volume  of 
Obermayer's  reagent  (p.  510),  and  the  indigo-blue  dissolved  by  means 
of  5  c.c.  of  chloroform.  The  chloroform  solution  is  then  compared 
colorimetrically  with  Fehling's  solution.  This  can  be  done  by  putting 
the  indigo  solution  and  5  c.c.  of  the  Fehling's  solution  respectively  into 
small  test-tubes  of  equal  calibre,  and  comparing  the  depth  of  tint. 
If  the  Fehling's  solution  is  stronger  than  the  indigo  solution,  run  water 
into  the  former  from  a  pipette,  graduated  in  tenths  of  a  c.c,  shaking 
up  after  each  addition,  till  equality  of  tint  has  been  reached.  If  the 
indigo  solution  has  a  stronger  blue  colour  than  the  Fehling's  solution, 
dilute  a  measured  amount  of  it  first  of  all  with  such  a  quantity  of 
chloroform  (say  an  equal  volume)  as  will  make  its  tint  distinctly  weaker 
than  that  of  the  Fehling's  solution.  Then  dilute  the  Fehling's  sclu-ion 
with  water,  as  before,  till  the  tint  is  the  same.  From  the  amou-it  of 
dilution  the  quantity  of  indigo  can  be  expressed  in  arbitral y  units, 
taking  Fehling's  solution  as  100.  Thus,  if  i  c.c.  of  water  must  be 
added  to  the  5  c.c.  of  Fehling's  solution,  the  indican  can  be  expressed 

as  ——  =  ^—==83.     The  comparison  can  be  made  more  accurately  by 

5 
a  colorimeter,  if  one  is  available.     To  determine  the  absolute  amount 
of  indigo  obtained,  comparison  must  be  made  with  a  standard  solution 
of  indigo. 

7.  Urea — (i)  Decomposition  of  Urea. — Heated  dry  in  a  test-tube,  it 
gives  off  ammonia.  The  residue  contains  biuret,  which,  when  dissolved 
in  water,  gives  a  rose  colour  with  a  trace  of  cupric  sulphate  and  excess 
of  sodium  hydroxide  (or  of  the  hydroxides  of  certain  other  metals  of 
the  alkalies  and  alkaline  earths  (p.  8).  Some  proteins — peptones  and 
albumoses — in  the  presence  of  the  same  reagents,  give  a  similar  colour, 
the  so-called  biuret  reaction. 

(2)  Quantitative  Estimation — Folin's  Method. — Put  3  c.c.  of  urine, 
20  grammes  of  magnesium  chloride,  and  2  c.c.  of  concentrated  hydro- 
chloric acid  into  an  Erlenmcycr  flask  of  200  c.c.  capacity  fitted  with  a 
short  backflow  tube  (200  mm.  long  and  10  mm.  in  diameter).  Add  a 
small  piece  of  paraffin  to  prevent  foaming.  Boil  briskly,  and  then 
continue  boiling  moderatily  for  fo:ty-five  to  sixty  minutes.  Now 
cautiously  dilute  the  mixture  with  water  and  wash  it  into  a  litre  flask. 
Add  about  7  c.c.  of  a  20  per  cent,  solution  of  sodium  hydroxide,  and 
distil  off  into  decinormal  acid.     Usually  about  350  c.c.  of  water  should 


512 


EXCRETION 


be  distilled  off,  which  takes  about  sixty  minutes.  Then  titrate  the 
acid  with  decinormal  alkali  (sodium  hydroxide).  Deduct  from  the 
number  of  c.c.  of  acid  taken  the  number  of  c.c.  of  the  decinormal  alkali 
needed  to  neutralize  it.  The  difference  gives  the  number  of  c.c.  of 
decinormal  ammonia  which  passed  into  the  acid.  Each  c.c.  of  deci- 
normal ammonia  contained  in  the  distillate  corresponds  to  3  mg.,  or 
o-i  per  cent,  of  urea.  Corrections  for  the  ammonia  content  of  the  mag- 
nesium chloride  used,  as  well  as  for  preformed  ammonia  in  the  urine, 
are  made  separately. 

A  less  exact  method  which  is  very  rapid,  and 
is  therefore  much  used  in  clinical  determinations,  is 
the  Hypohromite  Method.  The  urea  is  split  up  by 
sodium  hypobromite  (p.  474),  and  the  carbon  dioxide 
being  absorbed  by  the  excess  of  sodium  hydroxide  used 
in  preparing  the  hypobromite,  the  nitrogen  is  collected 
ovjr  water  in  an  inverted  burette.  It  is  easy  to  cal- 
cu'ate  the  weight  of  urea  corresponding  to  a  given 
volume  of  nitrogen  measured  at  a  given  temperature 
and  pressure.  The  nitrogen  of  urea  is  f§,  or  ^  of  the 
whole  molecular  weight.  Now,  i  c.c.  of  N  weighs,  at 
760  millimetres  of  mercury  and  0°  C,  0'00i25  gramme. 
Therefore,   i  c.c.  of   N  corresponds  to  o-ooi25x^^  = 


0-00268  gramme  urea.  Suppose,  now,  that  i  c.c.  of 
urine  was  found  to  yield  10  c.c.  of  N  measured  at  17°  C. 
and  750  millimetres  barometric  pressure. 
Since  a  gas  expands  ^^  part  of  its 
volume  at  0°  for  every  degree  above  o", 
we  must  correct  the  apparent  volume  of 
nitrogen  by  multiplying  by  ||^^.  Since 
the  volume  of  a  gas  is  inversely  propor- 
tional to  the  pressure,  we  must  further 
multiply  by  \^%.  Thus  we  get  10  x  'ilf^ 
xlf^%='^.f^^-^=g'2g  c.c.  as  the  volume 
of  the  nitrogen  reduced  to  0°  C.  and 
760  millimetres  of  mercury.  Multiplying 
this  by  0-00268,  we  get  0-0249  gramme 
urea  for  i  c.c.  urine,  which  for  a  daily 
yield  of  1,200  c.c.  would  correspond  to 
29-88  grammes  urea. 

As  a  matter  of  fact,  however,  it  has 
been  found  that  there  is  always  a  de- 
ficiency of  nitrogen — that  is,  a  given 
quantity  of  urea  yields  less  than  the 
estimated  amount  of  gas.  A  gramme  .of 
urea  in  urine,  insteadof  giving  off  373  c.c. 
of  nitrogen,  gives  only  354  c.c.  at  0°  C. 
and  760  millimetres  pressure..  We  must 
therefore  take  i  c.c.  of  Nas  correspond- 
ing to  0-00282  gramme,  instead  of  0-00268  gramme  urea.  But  it  is 
affectation  to  make  this  correction  if,  as  is  seldom  done  in  hospitals,  the 
temperature  is  not  taken  into  account. 

A  convenient  apparatus  is  shown  in  Fig.  194.  In  B  place  10  c.c. 
of  a  solution  made  by  adding  bromine  to  ten  times  its  volume  of  40  per 
cent,  sodium  hydroxide  solution.  Mix  5  c.c.  of  urine  with  5  c.c.  of 
water.  Put  5  c.c.  of  the  mixture  into  the  thimble  A,  which  is  then  set 
in  the  small  bottle  B.  The  cork  is  now  carefully  fixed  in  B,  and  the 
tube  F  being  open,  the  level  of  the  water  in  the  burette  is  read  off. 


Fig.  194. — Hypobromite  Method 
of  estimating  Urea.  A,  glass 
thimble;  B,  bottle,  through  the 
rubber  cork  of  which  pass  two 
short  glass  tubes,  one  connected 
by  the  rubber  tube  C  with  a 
burette  D,  and  the  other  armed 
with  a  short  piece  of  rubber  tube 
F.  F  is  provided  with  a  pinch- 
cock.  The  burette  is  supported 
on  a  stand,  and  immersed  in 
water  contained  in  the  glass 
cylinder  E. 


PRACTICAL  EXERCISES 


513 


The  pinchcock  having  been  closed,  the  bottle  B  is  now  tilted  so  that 
the  urine  in  the  thimble  is  gradually  mixed  with  the  hypobroraite 
solution,  and  the  nitrogen  given  off  is  added  to  the  air  in  the  burette 
and  its  connections.  The  level  of  the  water  in  the  burette  is  therefore 
depressed.  When  gas  ceases  to  be  given  off,  and  a  short  time  has  been 
allowed  for  the  whole  to  cool,  the  tube  is  raised  till  the  level  of  the 
water  is  once  more  the  same  inside  and  out.  The  level  is  again  read 
off;  the  difference  of  the  two  readings  gives  the  volume  of  nitrogen  at 
the  temperature  of  the  air  and  the  barometric  pressure.  In  order  that 
the  temperature  of  the  water  may  be  the  same  as  that  of  the  air,  the 
cylinder  should  be  filled  a  considerable  time  before  the  observations 
are  begun. 

For  most  clinical  purposes  sufficiently  accurate  results  may  be  very 
easily  obtained  with  the  so-called  ureometer  of  Doremus  (Fig.  195). 
A  little  urine  is  poured  into  the  side-tube  A,  the  stopcock  C  being  closed. 
The  stopcock  is  then  opened  for  an  instant,  so  as  to  fill  its  bore,  and 
then  closed  again.  Any  urine  which  has  passed  into  the  tube  B  is 
washed  out  with  water,  and  B  is  then  filled  with  hypobromite  solution. 
A  is  now  filled  up  with  urine  to  the  top  of  the 
graduation.  By  opening  the  stopcock,  i  c.c.  of 
urine  (or  less  if  the  urine  is  concentrated)  is  per- 
mitted to  pass  into  B  and  to  mix  with  the  hypo- 
bromite solution.  The  nitrogen  collects  in  B,  and 
when  it  has  ceased  to  come  off,  the  meniscus  of 
the  liquid  is  read  off.  The  corresponding  degree 
on  the  scale  gives  the  amount  of  urea  in  grammes 
contained  in  the  quantity  of  urine  employed. 

8.  Estimation  of  the  Ammonia  in  Urine  (Folin's 
Method). — Ammonia  is  liberated  by  addition  of  a 
weak  alkali  (sodium  carbonate).  Then  the  am- 
monia is  driven  out  at  ordinary  temperature  by  a 
strong  current  of  air  and  taken  up  in  decinormal 
acid,  which  is  then  titrated  with  decinormal  alkali. 

The  apparatus  employed  consists  of  —  (i)  A 
cylinder  of  about  45  cm.  height  and  5  cm.  diam- 
eter, with  a  rubber  stopper  through  which  pass 
two  glass  tubes.  One  of  the  tubes  goes  nearly  to 
the  bottom  of  the  cylinder,  and  the  other  end  is  connected,  through  a 
U-tube  filled  with  cotton,  with  a  tube  containing  sulphuric  acid.  The 
s-cond  tube  is  cut  off  short  below  the  rubber  cork,  and  its  other  end  is 
connected,  through  a  U-tube  containing  cotton,  with  a  sulphuric  acid 
tube  (or  with  two  in  series).  (2)  A  water-pump  to  draw  or  force  air 
through  the  apparatus  (600  to  700  litres  in  an  hour). 

Put  into  the  first  sulphuric  acid  tube  25  c.c,  into  the  second  10  c.c. 
decinormal  acid  and  some  water;  into  the  cylinder  2-,  c.c.  of  filtered 
urine,  8  to  10  grammes  sodium  chloride,  5  to  10  c.c.  of  petroleum  or 
toluol  to  prevent  foaming,  and  last  of  all  i  gramme  dried  sodium 
carbonate.  At  once  close  the  cylinder  and  allow  a  strong  stream  of  air 
to  pass  through  the  apparatus.  At  a  temperature  of  20°  to  25°  (room 
temperature),  and  using  6.00  to  700  litres  of  air  an  hour,  all  the  ammonia 
is  in  the  sulphuric  acid  in  one  to  one  and  a  half  hours.  The  contents 
of  the  sulphuric  acid  tubes  are  put  into  a  beaker  and  titrated  with 
decinormal  alkali,  using  lacmoid  (litmoid)  or  rosolic  acid  as  indicator. 
Deduct  the  number  of  c.c.  of  alkali  used  from  the  numb?r  of  c.c.  of  the 
decinormal  acid  originally  taken,  and  multiply  the  remainder  by  1*7034 
to  get  the  quantity  of  ammonia  in  milligrammes.  The  method  can  be 
employed  also  for  albuminous  urine. 

33 


Fig.  195. — Doremus 
Ureometer. 


514  EXCRETION 

9.  Estimation  of  the  Total  Nitrogen. — It  is  sometimes  more  important 
to  determine  the  total  nitrogen  of  the  urine  than  the  urea  alone.  This 
is  conveniently  done  by  Kjeldahl's  method  (or  some  modification  of 
it),  which  can  also  be  applied  to  the  estimation  of  the  nitrogen  in  the 
faeces,  or  in  any  of  the  solids  or  liquids  of  the  body.  It  depends  on  the 
oxidation  of  the  nitrogenous  matter  (or,  rather,  in  the  case  of  urine, 
mainlj,  its  hydrolysis)  in  such  a  way  that  the  nitrogen  is  all  represented 
as  ammonia.  The  ammonia  is  then  distilled  over,  collected  and  esti- 
mated, and  from  its  amount  the  nitrogen  is  easily  calculated.  In  urine 
the  method  can  be  carried  out  by  adding  to  a  measured  quantity  of  it 
(say  5  c.c.)  four  times  its  volume  of  strong  sulphuric  acid,  and  boiling 
in  a  long-necked  flask  (capacity  200  c.c),  after  the  addition  of  a  globule 
of  mercury  (about  o-i  c.c),  which  hastens  oxidation  and  obviates 
bumping.  A  parr  of  the  mercuric  sulphate  formed  remains  in  solution  ; 
the  rest  forms  a  crystalline  deposit.  The  heating  should  continue  for 
half  an  hour,  or  until  the  liquid  is  decolourized.  It  should  be  kept 
gently  boiling.  This  completes  the  process  of  oxidation ;  and  the  next 
step  is  to  liberate  the  ammonia  from  the  substances  with  which  it  is 
united  in  the  solution,  and  to  distil  it  over.  Dilute  the  liquid  with 
water,  after  cooling,  up  to  about  150  c.c,  and  pour  into  a  larger  long- 
necked  flask.  Add  enough  of  a  solution  of  sodium  hydroxide  (specific 
gravity  about  1*25)  to  render  the  liquid  alkaline,  avoiding  excess,  as 
this  favours  bumping.  The  proper  quantity  can  be  found  by  deter- 
mining beforehand  how  much  of  the  alkali  is  needed  to  neutralize  the 
acid  used  for  oxidation,  and  a  little  more  than  this  amount  should  be 
added.  Twenty  c.c.  of  strong  sulphuric  acid  needs  about  75  c.c.  of 
40  per  cent,  sodium  hydroxide  to  neutralize  it.  Bumping  may  further 
be  prevented  by  the  addition  of  a  little  granulated  zinc.  Shake  the 
flask  two  or  three  times.  Add  also  about  12  c.c.  of  a  concentrated 
solution  of  potassium  sulphide  (i  part  to  i^  parts  water),  which  favours 
the  setting  fiee  of  the  ammonia  from  the  amino-compounds  of  mercury 
that  have  been  formed  during  oxidation .  Commercial '  liver  of  sulphur  ' 
will  do  quite  well.  Immediately  connect  the  distilling-flask  with  a 
worm  or  Liebig's  condenser,  and  distil  the  ammonia  over  into  50  c.c. 
of  standard  (decinormal)  sulphuric  acid  (see  footnote,  p.  473)  con- 
tained in  a  flask  into  which  a  glass  tube  connected  with  the  lower  end 
of  the  worm  dips.  Heat  the  distilling-flask  at  first  gently,  then  strongly, 
and  boil  for  three-quarters  of  an  hour,  or  until  about  two-thirds  of  the 
liquid  has  passed  over.  Then  lift  the  tube  out  of  the  standard  acid,  and 
continue  the  distillation  for  two  or  thiee  minutes  longer.  The  ammonia 
is  now  all  united  with  the  standard  acid,  a  certain  amount  of  which  is 
left  over.  By  determining  this  amount  we  arrive  at  the  quantity  com- 
bined with  ammonia,  and  therefore  at  the  quantity  of  ammonia.  Fill 
a  burette  with  a  decinormal  solution  of  potassium  or  sodium  hydroxide. 
Add  a  little  methyl-orange  solution  to  the  standard  sulphuric  acid,  to 
serve  as  indicator.  Then  run  in  the  potassium  or  sodium  hydroxide 
till  the  pink  tinge  gives  place  to  a  permanent  but  just  recognizable 
yellow.  Let  x  be  the  number  of  c.c.  run  in.  Since  i  c.c.  of  any  deci- 
normal solution  is  equivalent  to  i  c.c.  of  any  other,  x  represents  also  the 
number  of  c.c.  of  the  standard  sulphuric  acid  left  uncombined  with 
ammonia;  and  50— at,  the  quantity  combined  with  ammonia.  Then, 
I  c.c.  of  decinormal  sodium  or  potassium  hydroxide  being  equivalent 
to  I  c.c.  of  decinormal  ammonium  hydroxide,  and  i  c.c.  of  decinormal 
ammonium  hydroxide  containing  0-0014  gramme  nitrogen,  we  get 
(50  —  x)x  0-0014  ^■s  the  quantity  of  nitrogen  in  5  c.c.  of  urine. 

Instead  of  mercury,  potassium  sulphate  and  copper  sulphate  may  be 
added  to  the  sulphuric  acid  in  order  to  aid  the  decomposition  in  the 


PRACTICAL  EXERCISES  515 

first  stage  of  the  estimation.  About  3  grammes  of  potassium  sulphate 
and  I  gramme  of  copper  sulphate  arc  added  to  5  c.c.  of  urine,  and  then 
5  c.c.  of  sulphuric  acid.  The  liquid  is  gently  boiled  for  an  hour,  or  until 
it  is  quite  clear.  The  neutralization  and  distillation  are  conducted  as 
before,  the  proper  quantity  of  sodium  hydroxide  being  determined  in 
advance.  No  potassium  sulphide  is  added,  but  a  small  quantity  of 
tile  may  be  put  in  to  prevent  bumping.  Instead  of  methyl  orange, 
'  alizarin  red,'  which  is  bright  red  in  the  presence  of  the  slightest  trace 
of  alkali,  may  be  used. 

10.  Uric  Acid — (i)  Qualitative  Test  for  Uric  Acid — Murexide  Test. — 
A  small  quantity  of  uric  acid  or  one  of  its  salts  is  heated  with  a  little 
dilute  nitric  acid.  The  colour  of  the  residue  left  by  evaporation 
b.'comcs  yellow,  and  then  red,  and  on  the  addition  of  ammonia  changes 
to  deep  purple-red.  Potassium  or  sodium  hydroxide  changes  the 
yellow  to  violet.  In  the  reaction  alloxantin  is  formed  by  oxidation  of 
the  uric  acid.  When  ammonia  acts  on  alloxantin  it  is  changed  into 
purpuric  acid,  and  this  into  its  ammonium  purpurate,  the  purple-red 
substance  called  murexide.     Thus: 

C8HeN408+  NH3  =C8H5N506  +  2H2O. 

Alloxantin.  Purpuric  Acid. 

The  reaction  is  also  given  by  theobromine  (dimethylxanthin),  an  alkaloid 
in  cocoa,  and  thcinc  or  caffeine  (trimethylxanthin),  an  alkaloid  in  tea 
and  coffee,  which  are  also  purin  derivatives  (p.  475). 

(2)  Quantitative  Estimation  —  Folin's  Modification  of  Hopkins's 
Method. — The  chief  reagent  is  a  solution  of  500  grammes  ammonium 
sulphate,  5  grammes  uranium  acetate,  and  60  c.c.  10  per  cent,  acetic 
acid,  in  650  c.c.  of  water. 

One  hundred  and  fifty  c.c.  of  urine  is  measured  into  a  tall,  narrow 
beaker  or  a  cylinder,  and  370-  c.c.  of  the  reagent  added.  If  enough 
urine  is  available,  200  c.c.  of  urine  and  50  c.c.  of  reagent  are  to  be  used. 
Allow  the  mixture  to  stand  without  stirring  for  about  half  an  hour. 
The  uranium  precipitate  has  then  settled,  and  the  clear  supernatant 
liquid  is  removed  by  siphoning  or  decantation.  One  hundred  and 
twenty-five  c.c.  of  this  liquid  is  measured  into  another  beaker,  5  c.c. 
of  strong  ammonia  added,  and  the  mixture  set  aside  till  next  day.  The 
precipitate  is  then  filtered  off,  and  washed  with  10  per  cent,  ammonium 
sulphate  solution  until  the  filtrate  is  t]^uite  or  nearly  free  from  chlorides. 
The  filter  is  then  removed  from  the  funnel,  opened,  and  the  precipitate 
rinsed  back  into  the  beaker.  Enough  water  to  make  about  100  c.c.  is 
added,  and  the  precipitate  is  then  dissolved  by  means  of  15  c.c.  con- 
centrated sulphuric  acid,  and  at  once  titrated  with  -J^jj  (one-twentieth 
normal)  potassium  permanganate  solution  (made  by  dissolving 
I -581  grammes  of  the  permanganate  in  a  litre  of  water),  each  c.c.  of 
which  corresponds  to  3-75  milligrammes  of  uric  acid.  The  very  first 
pink  coloration,  extending  through  the  entire  liquid  on  the  addi- 
tion of  two  drops  of  permanganate  solution,  marks  the  end  point. 
A  correction  of  3  milligrammes,  owing  to  tlie  solubility  of  ammonium 
urato,  is  added  to  the  result. 

11.  Kreatinin. — Qualitatively,  kreatinin  may  be  recognized  in  very 
small  amounts  by  Weyl's  test.  A  few  drops  of  a  dilute  solution  of 
sodium  nitro-prusside  are  added  to  urine,  and  then  dilute  sodium 
hydroxide  drop  by  drop.  A  ruby-red  colour  appears,  which  soon  turns 
yellow.  If  the  urine  is  now  strongly  acidified  with  acetic  acid  and 
heated,  it  becomes  first  greenish  and  then  blue.  Enough  acid  must  be 
added  to  more  than  neutralize  the  alkali. 

Another  test  which  has  been  made  the  basis  of  a  quantitative  method 


5i6  EXCRETION 

by  Folin  is  Jaffe's  test.  A  little  urine  (say  5  c.c.)  is  put  in  a  test-tube, 
and  then  a  solution  of  picric  acid  in  water.  The  mixture  is  rendered 
alkaline  by  the  addition  of  potassium  or  sodium  hydroxide  solution, 
and  a  reddish  colour  is  produced,  which  turns  yellow  on  .the  addition  of 
acid.  A  similar  red  colour  is  given  by  dextrose,  but  not  unless  the 
solution  is  heated. 

Quantitative  Estimation  of  Kreatinin  by  Folin' s  Method. — It  depends 
upon  the  comparison  of  the  colour  which  kreatinin  gives  with  picric 
acid  in  an  alkaline  solution  with  that  of  a  standard  solution  of  potassium 
bichromate.  Ten  c.c.  of  urine  is  measured  into  a  500  c.c.  measuring- 
flask;  15  c.c.  of  a  saturated  picric  acid  solution  (containing  about 
12  grammes  per  litre)  and  5  c.c.  of  a  10  per  cent,  solution  of  sodium 
hydroxide  are  added.  The  mixture  is  allowed  to  stand  for  five  minutes. 
Then  water  is  added  up  to  the  500  c.c.  mark,  and  the  flask  shaken  to 
mix  unifomily.  Samples  of  the  liquid  are  then  at  once  compared 
colorimetrically  with  a  half-normal  solution  of  potassium  bichromate 
containing  24'55  grammes  per  litre.  The  colour  of  the  urine  does  not 
introduce  a  sensible  error  on  account  of  the  great  dilution.  For  exact 
work  the  comparison  must  be  made  with  a  good  colorimeter.  It  has 
been  foimd  experimentally  that,  when  10  milligrammes  of  kreatinin 
are  present  in  500  c.c.  of  a  solution  made  as  described,  a  layer  of  the 
solution  8-1  millimetres  in  thickness  has  the  same  depth  of  tint  as  8  milli- 
metres of  the  bichromate  solution.  Suppose  it  takes  9  millimetres  of 
the  urine-picrate  solution  to  equal  8  millimetres  of  the  bichromate, 

8*1 
then    the    10    c.c.    of    urine    contains    10  x  —  =q'0    milligrammes    of 

9 
kreatinin. 

12.  Hippuric  Acid. — From  horse's  or  cow's  urine  hippuric  acid  is 
prepared  by  evaporating  to  a  small  bulk,  and  adding  strong  hydrochloric 
acid.  The  crystalline  precipitate  is  washed  with  cold  water,  then 
dissolved  in  hot  water,  and  filtered  hot.  Hippuric  acid  separates  out 
from  the  filtrate  in  the  cold  in  the  form  of  long  four-sided  prisms  with 
pyramidal  ends.  Heated  dry  in  a  test-tube,  the  crystals  melt,  and 
benzoic  acid  and  oily  drops  of  benzonitrile,  a  substance  with  a  smell 
like  that  of  oil  of  bitter  almonds,  are  formed. 

ABNORMAL    SUBSTANCES    IN    URINE. 

13.  Proteins — (i)  Qualitative  Tests. — (a)  Boil  and  add  a  few  drops 
of  nitric  acid.  A  precipitate  on  boiling,  increased  or  not  affected  by 
the  acid,  shows  the  presence  of  coagulable  proteins  (serum-albumin  or 
globulin).  A  precipitate  of  earthy  phosphates  sometimes  forms  on 
boiling.  It  is  distinguished  from  a  precipitate  of  proteins  by  dissolving 
on  the  addition  of  acid. 

{b)  Heller's  Test. — Put  some  nitric  acid  in  a  test-tube.  Pour  care- 
fully on  to  the  surface  of  the  acid  a  little  urine.  A  white  ring  at  the 
junction  of  the  liquids  indicates  the  presence  of  albumin  or  globulin. 
If  much  albumose  is  present,  a  white  precipitate,  which  disappears  on 
heating,  may  be  formed.  When  this  test  is  performed  with  undiluted 
urine,  uric  acid  may  be  precipitated  and  cause  a  brown  colour  at  the 
junction.  A  similar  ring  may  be  found  in  the  absence  of  proteins  when 
the  test  is  made  on  the  urine  of  a  patient  who  has  been  taking  copaiba. 
In  very  concentrated  urine  a  white  ring  of  nitrate  of  urea  may  be 
formed.  A  coloured  ring  is  frequently  seen,  owing  to  the  oxidation  of 
certain  chromogens  of  urine. 

[c)  Filter  some  urine,  and  add  to  the  filtrate  its  own  volume  of  acetic 
acid      A  precipitate  may  indicate  mucin  or  nucleo-albumin.     If  any  is 


PRACTICAL  EXERCISES  517 

formed,  filter  it  off,  and  add  to  the  filtrate  a  few  drops  of  potassium 
ferrocyanide.     A  white  precipitate  shows  the  presence  of  proteins. 

{d)  Test  for  Globulin  in  Urine.  —  Serum-globulin  probably  never 
occurs  in  urine  apart  from  serum-albumin.  It  may  be  detected  thus: 
Make  the  urine  alkaline  with  ammonia,  let  it  stand  for  an  hour,  and 
filter.  Half  saturate  the  filtrate  with  ammonium  sulphate — i.e.,  add 
to  it  an  equal  volume  of  a  saturated  solution  of  ammonium  sulphate. 
Serum-globulin  is  precipitated,  serum-albumin  is  not. 

{e)  Test  for  Alburnose  in  Urine  {Albumosuria). — Coagulable  proteins 
are  removed  by  boiling  the  urine  (acidulated  if  necessary),  and  filtering 
off  the  precipitate  if  any.  The  filtrate  is  neutralized.  If  a  further 
precipitate  falls  down  it  is  filtered  off,  the  clear  filtrate  is  heated  in  a 
beaker  placed  in  a  boiling  water-bath,  and  there  saturated  with  crystals 
of  ammonium  sulphate.  A  precipitate  indicates  that  albumoses 
(proteoses)  are  present.  A  slight  precipitate  might  possibly  be  due  to 
the  formation  of  ammonium  urate.  A  further  test  may  be  performed 
on  the  original  urine  if  it  is  free  from  coagulable  proteins,  or  on  the 
filtrate  after  their  removal.  Add  a  drop  or  two  of  pure  nitric  acid. 
If  albumoses  are  present,  a  precipitate  is  thrown  down  which  disappears 
on  heating,  and  reappears  on  cooling  the  test-tube  at  the  cold-water  tap. 

(2)  Quantitative  Estimation  of  Coagulable  Proteins  [Serum-Albumin 
and  Globulin) — (a)  Gravimetric  Method. — Heat  50  to  100  c.c.  of  the 
urine  to  boiling,  adding  a  dilute  solution  (2  per  cent.)  of  acetic  acid  by 
drops  as  long  as  the  precipitate  seems  to  be  increased.  Filter  through 
a  weighed  filter.  Wash  the  precipitate  on  the  filter  with  hot  water, 
then  with  hot  alcohol,  and  finally  with  ether.  Dry  in  an  air-bath  at 
110°  C,  and  weigh  between  watch-glasses  of  known  weight. 

(6)  Esbach's  Method. — Esbach's  reagent  is  made  by  dissolving 
10  grammes  r  f  picric  acid  and  20  grammes  of  citric  acid  in  boiling 
water  (800  or  900  c.c),  and  then  making  up  the  volume  to  a  litre.  The 
so-called  albuminimetcr  is  simply  a  strong  glass  tube  graduated  and 
marked  in  a  certain  way.  Fill  the  tube  up  to  the  mark  U  with  the 
urine.  Then  add  the  reagent  up  to  the  mark  R.  Close  the  tube  with 
the  rubber  cork,  and  invert  it  a  dozen  times  without  shaking.  Set  the 
tube  aside  for  twenty -four  hours,  then  read  off  the  graduation  on  the 
tube  which  corresponds  with  the  top  of  the  precipitate.  The  figures 
indicate  the  number  of  grammes  of  dry  protein  in  a  litre  of  the  urine. 
Suppose  the  top  of  the  sediment  is  at  4 ,  this  will  indicate  4  grammes  per 
litre,  or  0*4  per  cent.  The  method  is  of  some  clinical  importance,  owing 
to  its  simplicity,  althc  ugh  it  is,  of  course,  not  very  accurate. 

14.  Sugar — (i)  Qualitative  Tests — (a)  Trammer's  Test  (p.  10). — It  is  to 
be  remarked  that  some  substances  present  in  small  amount  in  normal 
urine  reduce  cupric  sulphate — e.g.,  uric  acid  (present  as  urates)  and 
kreatinin — but  although  a  normal  urine  may  thus  decolourize  the 
copper  solution,  it  rarely  causes  so  much  reduction  that  a  yellow  or  red 
precipitate  is  formed,  as  is  the  case  in  diabetic  urine.  Glycuronic  acid 
(p.  47O)  also  reduces  cupric  salts,  as  docs  alcapton  or  homogentisinic 
acid,  a  substance  found  in  rare  cases  in  disease  (p.  477). 

(6)  Fehling's  Test. — Fehling's  solution  (p.  518)  is  brought  to  the  boil  ill 
a  test-tube,  a  little  of  the  urine  then  added,  and  the  change  of  colour 
noted.  Benedict's  modification  of  Fehling's  solution  may  also  be  used. 
It  has  the  advantage  that  it  keeps  indefinitely,  and  therefore  is  always 
ready  for  use,  and  is  also  said  to  be  more  delicate. 

(c)  Phenyl-Hydrazine  Test. — This  test  depends  upon  the  fact  that 
phenyl-hydrazine  forms  with  sugars  such  as  glucose  (dextrose),  maltose, 
isomaltose,  etc.,  but  not  with  cane-sugar,  characteristic  crj-stalline 
substances   (phenyl-glucosazone,   phenyl-maltosazone,  etc.)  which  Ccin 


5i8 


EXCRETION 


be  recognized  under  the  microscope,  and  are  distinguished  from  each 
other  by  melting  at  different  temperatures.  Phenyl-glucosazone 
(C18H22N4O4)  melts  at  205°  C.  To  perform  the  test  for  dextrose  in  the 
urine,  proceed  thus:  Put  5  c.c.  of  urine  in  a  test-tube,  add  i  decigramme 
of  hydrochlorate  of  phenyl-hydrazine  and  2  decigrammes  of  sodium 
acetate.  It  is  sufficiently  accurate  to  add  as  much  phenyl-hydrazine 
as  will  lie  on  a  sixpence  (or  a  dime)  and  twice  as  much  sodium  acetate. 
Heat  the  test-tube  in  a  boiling  water-bath  for  half  an  hour.  Then  cool 
at  the  tap  and  examine  the  deposit  under  the  microscope  for  the  yellow 
phenyl-glucosazone  crystals  (Fig.  196).  Sometimes  the  osazone  pre- 
cipitate is  amorphous.  If  this  should  be  the  case,  the  precipitate,  if  no 
crystals  can  be  seen,  must  be  dis.solved  in  hot  alcohol.  The  solution  is 
then  diluted  with  water  and  the  alcohol  boiled  off,  when  the  osazone, 

if  any  be  present,  will  crystallize  out. 
Very  minute  traces  of  sugar  can  be 
detected  in  this  way  (as  little  as  o-i  per 
cent,  in  urine).  Often  in  normal  urine 
yellow  crystals  are  deposited  during 
the  first  fifteen  minutes'  heating. 
They  must  not  be  mistaken  for  gluco- 
sazone.  They  probably  consist  of  a 
compound  of  glycuronic  acid  and 
phcn3d-hydrazine.  They  are  changed 
as  the  heating  goes  on  into  an  amor- 
phous brownish  -  yellow  precipitate 
(Abel). 

[d)  The  Yeast  Test  is  an  important 
confirmatory  test  for  distinguishing 
the  fermentable  sugars  from  other  re- 
ducing substances,  but  it  is  not  very 
delicate ,  and  will  with  difficulty  detect 
sugar  when  less  than  0-5  per  cent,  is 
present.  It  can  be  performed  thus: 
A  little  yeast  (the  tablets  of  com- 
pressed yeast  do  very  well)  is  added 
to  a  test-tube  half  filled  with  urine. 
The  test-tube  is  then  filled  up  with 
mercury,  closed  with  the  thumb,  and 
inverted  over  a  dish  containing  mer- 
cury. The  dish  may  be  placed  on  the 
top  of  a  water-bath  whose  temperature 
is  about  40°  C.  After  twenty-four 
hours  the  sugar  will  have  been  broken 
up  into  alcohol  and  carbon  dioxide.  The  latter  will  have  collected 
above  the  mercury  in  the  test-tube,  and  the  former  will  be  present  in 
the  urine.  The  tests  for  sugar  will  either  be  negative  or  will  be  less 
distinct  than  before.  A  control  test-tube  containing  water  and  yeast 
should  also  be  set  up,  as  impurities  in  the  yeast  sometimes  yield  a  small 
amount  of  carbon  dioxide.  Specially-constructed  tubes  are  also  often 
used  for  performing  the  test. 

(2)  Quantitative  Estimation  of  Sugar  in  Urine. — (a)  V olumetrically , 
the  sugar  can  be  estimated  by  titration  with  Fehling's  solution.  As 
this  does  not  keep  well,  two  solutions  containing  its  ingredients  should 
be  kept  separately  and  mixed  when  required.  Solution  I.:  Dissolve 
34-64  grammes  pure  cupric  sulphate  in  distilled  water,  and  make  up  the 
volume  to  500  c.c.  Solution  II.:  Dissolve  173  grammes  Rochelle  salt 
in  400  c.c.  of  water,  add  to  this  51 -6  grammes  sodium  hydroxide,  and 


Fig.  196. — Phenyl-Glucosazone  and 
Phenyl-Maltosazone  Crystals  (Mac- 
leod).  The  phenyl  -  glucosazone 
crystals  are  in  the  upper  part  of 
the  figure,  the  phenyl-maltosazone 
in  the  lower. 


PRACTICAL  EXERCISES  5I9 

make  up  the  volume  with  water  to  500  c.c.  -K'^cp  in  wcll-stoppcrcd 
bottles  in  the  dark.  For  use,  mix  together  equal  volumes  of  the  two 
solutions.  Ten  c.c.  of  this  mixture  is  reduced  by  0-05  gramme  dextrose. 
To  estimate  the  sugar  in  urine,  put  10  c.c.  of  the  mixture  into  a  porcelain 
capsule  or  glass  flnsk,  and  dilute  it  four  or  five  times  with  distilled  water. 
Dilute  some  of  the  urine,  say  ten  or  twenty  times,  according  to  the 
quantity  of  sugar  indicated  by  a  rough  determination.  Run  the 
diluted  urine  from  a  burette  into  the  Fehling's  solution,  bringing  it  to 
the  boil  each  time  urine  is  added,  until,  on  allowing  the  precipitate 
to  settle,  the  blue  colour  is  seen  to  have  entirely  disappeared  from  the 
supernatant  liquid.  The  observation  of  the  colour  must  be  made  while 
the  liquid  is  still  hot.  Benedict's  modification  of  Fehling's  solution* 
may  also  be  employed. 

Suppose  that  10  c.c.  of  Fehling's  solution  is  decolourized  by  20  c.c. 
of  the  ten-times  diluted  urine.  Then  2  c.c.  of  the  original  urine  contains 
0-5  gramme  dextrose.  If  the  urine  of  the  twenty-four  hours  (from 
which  thi.s  sample  is  assumed  to  have  been  taken)  amounts  to  4.000  c.c, 
the  patient  will  have  passed  0-05x2,000=100  grammes  sugar,  in 
twenty-four  hours. 

[b)  The  polayimeter  affords  a  rapid  and,  with  practice,  a  delicate 
means  of  estimating  the  quantit}-  of  sugar  in  pure  and  colourless  solu- 
tions, but  diabetic  urine  must  in  general  be  first  decolourized  by  adding 
lead  acetate  and  filtering  off  the  precipitate.  What  is  measured  is  the 
amount  by  which  the  plane  of  polarization  of  a  ray  of  polarized  light  of 
given  wave-length  (say  sodium  light)  is  rotated  when  it  passes  through 
a  layer  of  the  urine  or  other  optically  active  solution  of  knowTi  thickness. 
Let  a  be  the  observed  angle  of  rotation,  /  the  length  in  decimetres  of 
the  tube  containing  the  solution,  w  the  number  of  grammes  of  the 
optically  active  substance  per  c.c.  of  solution,  and  {a)n  the  specific 
rotation  of  the  substance  for  light  of  the  wave-length  of  the  part  of  the 
spectrum  corresponding  to  the  D  line  {i.e.,  the  amount  of  rotation 
expressed  in  degrees  which  is  produced  by  a  layer  of  the  substance 
I  decimetre  thick,  when  the  solution  contains  i  gramme  of  it  per  c.c). 

Then   {a)a=±—..     In  this  equation  a  and  /  are   known   from  direct 

measurement;  {a)o  has  been  determined  once  for  all  for  most  of  the 
important  active  substances,  and  therefore  w  is  easily  calculated.  For 
dextrose  {a)a  may  be  taken  as  52-6°.  It  varies  somewhat  with  the 
concentration,  but  for  most  investigations  on  the  urine  these  variations 
may  be  neglected. 

It  is  net  possible  to  describe  here  the  numerous  forms  of  polarimeter 
that  are  in  use.  Those  constructed  on  what  is  called  the  '  half-shadow  ' 
system  (Fig.  197)  give  sufficiently  satisfactory  results.  A  half-shadow 
polarimeter  consists,  like  other  polarimeters,  of  a  fixed  Nicol's  prism 
(the  polarizer),  and  a  nicol  capable  of  rotation  (the  analyzer).  In 
addition,  there  is  an  arrangement  which  rotates  by  a  definite  angle  the 
plane  of  polarization  in  one-half  of  the  field,  but  not  in  the  other — 
e.g.,  a  small  nicol  occupying  only  half  of  the  field.  In  the  zero  position 
of  the  analyzer,  both  halves  of  the  field  arc  equally  dark.  The  solution 
to  be  investigated  is  placed  in  a  tube  of  known  length,  the  ends  of  which 

*  It  contains  ij'^  grammes  of  cup  i':  sulphate,  17.V0  grammes  of  sodium 
citrate,  1000  grammes  of  anhydrous  sodium  carbonate  made  up  with 
distilled  water  exactly  to  one  litre.  In  making  the  solution  the  citrate  and 
carbonate  are  dissolved  with  the  aid  of  heat  in  about  600  c.c.  of  water,  and 
then  made  up  to  about  800  c.c.  The  cupric  sulphate  is  dissolved  in  about 
100  or  150  c.c.  of  water  and  added  to  the  other  solution,  the  whole  be-rg  tlicn 
made  up  to  a  litre. 


520 


EXCRETION 


are  closed  by  glass  discs'sccurcd  by  brass  screw  caps.  The  glass  discs 
must  be  slid  on,  so  as  to  exclude  all  air.  The  tube  having  b?cn  intro- 
duced between  the  polarizer  and  analyzer,  the  sharp  vertical  line  which 
indicates  the  division  between  the  two  half-fields  is  focussed  with  the 
eye-piece,  and  then  the  analyzer  is  rotated  till  the  two  halves  are  again 
equally  shadowed.  The  angle  of  rotation,  a.  is  read  off  on  the  graduated 
arc,  which  is  provided  with  a  vernier. 

Pentoses  reduce  Fehling's  solution,  but  do  not  give  the  yeast  test. 
They  give  the  following  characteristic  tests,  which  may  be  performed 
with  gum  arable,  a  substance  containing  arabinose,  one  of  the  pentoses: 

(i)  Phloroglucin  Reaction. — Warm  in  a  test-tube  some  pure  concen- 
trated hj'drochloric  acid  to  which  an  equal  volume  of  distilled  water 
has  been  added.     Add  phloroglucin  tmtil  a  little  remains  undissolved. 


Fig.  197. — Mitscherlich's  Polarimeter.      (Half  shadow  instrument.)     (Simple  f or. n.) 


Add  a  small  quantity  of  gum  arable,  and  keep  the  test-tube  in  a  water- 
bath  at  100°  C.  The  solution  becomes  cherry-red,  and  a  precipitate 
gradually  separates,  which  may  be  dissolved  in  amyl  alcohol.  The 
solution  shows  with  the  spectroscope  a  band  between  D  and  E. 

(2)  Orcin  Reaction. — Use  orcin  instead  of  phloroglucin  in  (i).  The 
solution  becomes  reddish-blue  on  warming,  and  shows  a  band  between 
C  and  D,  near  D.  The  colour  quickly  changes  from  violet  to  blue,  red, 
and  finally  green.  A  bluish-gr^en  precipitate  separates,  which  is 
soluble  in  amyl  alcohol.  Glycuronic  acid  gives  all  the  above  reactions 
of  pentoses. 

Bile-Salts  {Hay's  Test). — Put  a  little  finely-divided  sulphur,  in  the 
form  of  flowers  of  sulphur,  on  the  top  of  a  glass  of  urine.  If  bile-salts 
are  present  the  sulphur  will  sink  to  the  bottom.     If  there  are  no  bile- 


PRACTICAL  EXERCISES  521 

salts  it  will  float  on  the  top.  The  difference  is  du2  to  an  alteration  in 
the  surface  tension  of  the  urine  produced  by  the  bile-salts.  We  must 
exclude  the  presence  of  acetic  acid,  alcohol,  ether,  chloroform,  turpen- 
tine, benzine  and  its  derivatives,  phenol  and  its  derivatives,  anilin  and 
soaps,  all  of  which  also  cause  such  an  alteration  in  the  surface  tension 
of  urine  tliat  the  sulphur  sinks  to  the  bottom.  The  urine  should  be 
fresh,  and  if  it  has  to  be  kept  it  should  be  preserved  from  decomposition 
by  cyanide  of  mercury,  which  does  not  alter  the  surface  tension.  The 
reaction  has  the  great  advantage  over  other  tests  of  being  easily  carried 
out  at  the  bedside. 

Acetone — (i)  LegaVs  Test  (Rothera's  modification). — To  5  to  10  c.c. 
of  the  acetone-containing  urine  add  enough  ammonium  sulphate  crystals 
to  form  a  layer  at  the  bottom  of  the  test-tube,  then  2  or  3  drops  cf 
a  fresh  5  per  cent,  solution  of  sodium  nitro-prusside  and  i  to  2  c.c.  of 
strong  ammonia.  The  development  of  a  colour  like  that  of  perman- 
ganate of  potassium,  often  in  the  form  of  a  ring  a  little  above  the 
undissolved  salt,  indicates  the  presence  of  acetone.  The  reaction  must 
not  be  declared  negative  till  half  an  hour  has  elapsed.  The  colour 
slowly  fades. 

(2)  Where  there  is  doubt  as  to  the  presence  of  acetone,  it  is  best  first 
to  distil  it  over.  Put  250  to  500  c.c.  of  the  urine  suspected  to  contain 
acetone  into  a  litre  flask.  Add  a  few  c.c.  of  phosphoric  acid;  connect 
the  flask  with  a  worm,  and  distil  over  the  urine  into  a  small  flask. 
For  qualitative  tests  it  is  best  to  collect  only  the  first  20  to  30  c.c, 
as  most  of  the  acetone  is  contained  in  this.  Test  the  distillate  for 
acetone  by  (i)  or  by 

Lieben's  Test. — To  a  few  c.c.  of  the  distillate  in  a  test-tube  add  a  few 
drops  of  solution  of  iodine  in  potassium  iodide,  and  then  sodium  or 
potassium  hydroxide.  A  precipitate  of  yellow  iodoform  crystals  (six- 
sided  tables)  is  thrown  down  if  acetone  be  present.  Examine  them 
under  the  microscope.  On  heating,  the  odour  of  iodoform  may  be 
recognized.  If  the  precipitate  is  amorphous  it  may  be  dissolved  in 
ether  (free  from  alcohol),  which  is  allowed  to  evaporate  on  a  slide, 
when  crj'stals  may  be  obtained. 

Determination  of  the  Freezing-Point  of  Urine. — Study  Beckmann's 
apparatus  shown  in  Fig.  171,  p.  421.  Note  the  large  thermometer  D 
graduated  in  hundredths  of  a  degree  centigrade.  It  is  inserted  through 
a  rubber  cork  into  the  inner  thick  test-tube  A.  A  platinum  wire  F,  bent 
at  the  lower  end  into  a  circle  or  a  spiral,  which  passes  easily  up  and 
down  between  the  bulb  of  the  thermometer  and  the  tube,  serves  to  stir 
the  urine.  The  thermometer  must  be  so  supported  by  the  rubber 
cork  that  the  bulb  is  in  the  axis  of  the  tube  and  a  centimetre  or  two  from 
the  bottom  of  it.  The  side-piece  E  on  the  tube  A  is  not  absolutely 
necessary,  but  it  is  convenient  for  'inoculating '  the  urine  with  a  crj-st^d 
of  ice  at  the  proper  time.  A  passes  through  a  rubber  cork  into  a  shorter 
and  wider  outer  glass  tube  B.  The  space  between  A  and  B  serves  as  a 
badly  conducting  mantle,  which  prevents  too  rapid  cooling  of  the 
contents  of  A.  B  passes  through  a  hole  in  the  metal  or  wooden  cover 
of  a  strong  glass  jar  C,  which  contains  the  freezing  mixture.  B  should 
fit  the  hole  so  tightly  that  it  docs  not  bob  up  out  of  the  mixture  when 
A  is  removed.  In  C  is  a  stirrer,  G,  of  strong  copper  wire,  the  end  of 
which  passes  through  the  lid.  This  serves  to  stir  up  the  freezing 
mixture  from  time  to  time. 

Pulverize  some  ice  by  pounding  it  in  a  strong  wooden  box  with  a 
heavy  piece  of  wood.  Take  the  inner  tube  with  the  thermometer  out 
of  the  apparatus.  It  is  convenient  to  take  the  thermometer  out  of  the 
tube,  and  to  hang  it  up  carefully  on  a  stand  by  means  of  a  fine  flexible 


522  EXCRETION 

copper  wire  passing  through  the  eye.  The  rubber  cork  can  be  taken 
out  witli  the  thermometer,  and  the  platinum  wire  also,  the  bent  free 
end  of  the  latter  supporting  it  in  the  cork,  or  it  may  be  fastened  tempor- 
arily to  the  thermometer  stem  by  a  small  rubber  band,  which  is  slid 
up  over  the  cork  when  the  thermometer  is  reinserted.  Tube  A  can  be 
set  temporarily  in  a  specially  heavy  test-tube  rack.  Remove  the  lid 
of  C,  and  with  it  tube  B.  Now  put  ice  and  salt  alternately  into  C  until 
it  is  nearly  full,  mixing  them  up  well.  Add  some  cold  water  from  the 
tap  till  the  stirrer  G  can  move  freely  up  and  down  in  the  mixture.  For 
very  exact  work  the  temperature  of  the  freezing  mixture  must  not  be 
more  than  a  few  degrees  below  the  freezing-point  of  the  liquid  which  is 
being  examined.  Put  on  the  lid,  and  immerse  tube  B.  Into  A,  which 
must  be  perfectly  clean,  put  enough  pure  distilled  water  to  fully  covet 
the  bulb  of  the  thermometer,  and  introduce  the  latter.  For  ordinary 
purposes  distilled  water  previously  boiled  to  expel  the  carbon  dioxide, 
and  then  cooled  in  a  stoppered  flask,  is  sufficiently  pure.  Immerse  A 
directly  in  the  freezing  mixture  through  the  hole  by  which  G  comes  out, 
or  through  a  separate  hole  (not  shown  in  the  figure)  till  some  ice  has 
formed  in  the  water.  Take  A  out  of  the  mixture,  wipe  it  with  a  cloth, 
and  hold  the  lower  part  of  it  in  the  hand  till  nearly  the  whole  of  the 
ice  has  melted.  If  there  is  a  cake  of  ice  at  the  bottom,  see  that  it  is 
displaced  by  the  platinum  stirrer.  A  trace  of  ice  being  still  left  floating 
in  the  water,  place  A  in  B,  and  allow  the  temperature  to  fall  to  a  few 
tenths  of  a  degree  below  the  freezing-point  you  expect  to  get,  as  deter- 
mined by  a  previous  rough  experiment.  The  freezing  mixture  is 
stirred  up  occasionally.  The  meniscus  of  the  thermometer  is  to  be 
carefully  followed,  as  it  goes  on  falling,  by  means  of  a  weak  hand  lens. 
Now  stir  the  water  in  A  briskly.  Suddenly  it  will  be  seen  that  the 
mercury  begins  to  rise.  Keep  stirring  with  the  platinum  wire,  and 
read  off  the  maximum  height  of  the  mercury,  at  which  it  is  stationary 
for  some  time.  The  temperature  can  be  estimated  between  the  gradu- 
ations to  thousandths  of  a  degree.  Take  out  A,  and  observe  the  fine 
ice  crystals  in  the  water.  Heat  A  in  the  hand  as  before  till  nearly  all 
the  ice  has  disappeared;  then  replace  A  in  B,  and  make  another  freezing- 
point  determination.  A  third  one  may  also  be  made,  and  the  mean 
of  the  three  readings  taken. 

Take  out  the  thermometer,  and  dry  it  and  the  platinum  wire  with 
clean  filter-paper,  or  dip  them  in  some  of  the  urine,  which  is  then  thrown 
away.  Dry  A  or  rinse  it  with  urine.  Then  make  a  determination  of 
the  freezing-point  of  the  urine  in  the  same  way  as  was  done  with  the 
water.     The  freezing-point  of  the  urine  will  lie  much  lower  on  the  scale. 

Instead  of  freezing  the  liquid  first  and  then  leaving  a  little  ice  in  it 
when  A  is  placed  in  B,  A  may  be  put  into  B  before  any  ice  has  formed. 
Cooling  is  then  allowed  to  go  on  with  gentle  stirring  to  a  few  tenths  of 
a  degree  below  the  anticipated  freezing-point.  A  small  crystal  of 
clean  dry  ice  is  then  introduced  through  the  side-piece  on  a  clean 
splinter  of  wood  or  the  loop  of  a  cooled  platinum  wire,  the  end  of  which 
passes  through  a  piece  of  cork,  by  which  it  is  held  to  prevent  conduction 
of  heat.  The  platinum  stirrer  can  be  raised  to  receive  the  crystal.  The 
liquid  is  now  vigorously  stirred ;  freezing  occurs,  and  the  observation  is 
made  as  before. 

Instead  of  the  above  method,  the  liquid  may  first  be  cooled  directly 
in  the  freezing  mixture,  but  not  so  much  that  ice  forms.  A  is  then  put 
in  B,  and  cooling  allowed  to  go  on  while  it  is  being  stirred.  When  it 
has  been  undcrcooled  to  a  certain  extent — i.e.,  cooled  below  its  freezing- 
point — the  vigour  of  the  stirring  is  increased.  Ice  forms  suddenly,  as 
before,  and  the  temperature  rises  to  the  freezing-point.     With  urine 


PRACTICAL  EXERCISES 


523 


this  method  is  sufficiently  satisfactory,  but  it  is  not  usually  easy  to  get 
freezing  of  the  distilled  water  till  the  undercooling  is  considerable,  and' 
it  has  been  shown  that  this  introduces  some  error. 

Suppose  the  freezing-point  of  the  distilled  water  on  the  scale  of  the 
thermometer  was  5-245  and  that  of  the  urine  3-625°,  the  value  of  A 
for  the  urine  is  1-620°.  Since  for  most  purposes  it  is  sufficient  to  fix 
the  second  decinial  point,  much  smaller  and  less  expensive  thermometers 
than  the  ordinary  Bcckmann  may  be  employed. 

In  the  same  way  the  freezing-point  of  blood-serum  (or  blood),  bile, 
and  other  phy.siological  liquids  can  be  determined. 

Systematic  Examination  of  Urine. — In  examining  urine,  it  is  con- 
venient to  adopt  a  regular  plan,  so  as  to  avoid  the  risk  of  overlooking 
anything  of  importance.  The  following  simple  scheme  may  serve  as 
an  example;  but  no  routine  should  be  slavishly  followed,  the  object 
being  to  get  at  the  important  facts  with  the  minimum  of  labour.  ]\Iore 
extensive  information  must  be  sought  in  the  treatises  on  examination 
of  the  urine  for  clinical  purposes. 

1.  Anything  peculiar  in  colour  or  smell  ?  If  the  colour  suggests 
blood,  examine  with  spectroscope,  hsemin  test,  guaiacum  tc-  (pp.  76, 
267) ;  if  it  suggests  bile,  test  for  bile-pigments  by  Gmelin's  test  (p.  456), 
and  for  bile-salts  by  Pettenkofer's  test  (p.  456)  and  by  Hay's  test 
(PP-  456,  520). 

2.  Reaction. 

3.  Sediment  or  not  ?  Sediment  may  be  procured  by  letting  the 
urine  stand  in  a  conical  glass,  or  in  a  few  minutes  by  the  centrifuge. 
If  the  appearance  of  the  sediment  suggests  anything  more  than  a  little 
mucus,  examine  with  the  microscope.  The  sediment  may  contain 
organized  or  unorganized  deposits. 

Organized  Sediments.— (a)  Red  blood-corpuscles  (considerably  altered 
if  they  have  come  from  the  upper  part  of  the  urinary  tract). 

(6)  Leucocytes.  A  few  are  present  in  health.  A  large  number 
indicates  pus.  When  pus  is  present  the  sediment  may  be  white  to  the 
naked  eye. 

(c)  Epithelium  from  the  bladder,  ureters,  pelvis  of  the  kidney  or  the 
renal  tubules.  A  few  squamous  epithelial  cells  from  the  urethra  are 
always  present  in  normal  urine. 

{d)  Tube  casts. 

(e)   Spermatozoa  (occasional). 

(/)  Bacteria. 

(§■)  Parasites  (rare). 

{h)  Portions  of  tumours  (rare) . 

Unorganized  Sediments. 


IN    ACID    URINE. 

Uric  Acid.— Cry ^i^\s  coloured 
brownish  -  yellow  with  urinary 
pigment.  Various  shapes,  espe- 
cially oval  '  whetstones,'  rhom- 
bic tables,  and  elongated  cr^-stals, 
often  in  bundles  (Fig.  177). 

Urates. — Usually  amorphous,  in 
the  form  of  fine  granules,  often 
tinged  with  urinary  pigment, 
sometimes  brick-red.  Soluble  on 
heating.  On  addition  of  acids 
(including  acetic   acid)   they  dis- 


IN    ALKALINE    URINE. 

Triple  Phosphate. — Clear,  col- 
ourless, coffin  -  lid  or  knife  -  rest 
crystals.  Also  deposited  in  the 
form  of  feathery  stars  (Fig.  179). 

Calcium  Hvdrogen  Phosphate 
('  stellar  '  phosphate),  CaHPOj.— 
Cny'stals  often  wedge-shaped  and 
arranged  in  rosettes.  Alay  also 
occur  in  a  dumb-beU  form.  (A 
phosphate  of  calcium  is  al«o  occa- 
sionally seen  in  weakly  acid  urine.) 
(Fig.  181.  p.  473.) 


524 


EXCRETION 


Unorganized  Sediments  {continued) — 


IN    ACID    URINE. 

solve  and  uric  acid  cystals  appear 
in  their  place.  Acid  urate  of 
sodium  and  of  ammonium  occa- 
sionally found  in  the  crystalline 
form  (rosettes  of  needles). 

Calcium  Oxalate. — Octahedral, 
'  envelope  '  crystals,  not  coloured. 
Insoluble  in  acetic  acid.  Soluble 
in  hydrochloric  acid  (Fig.  178, 
p.  472). 

Cystin.  —  Hexagonal  plates. 
Rire  (Fig.  180,  p.  473). 

Leucin  and  Tyrosin  (Figs.  186, 
187,  p.  483). — Rare.  Also  found 
in  alkaline  urine,  but  rarely. 

Triple  Phosphate.  —  Sometimes 
found  in  weakly  acid  urine. 


IN    ALKALINE    URINE. 

Calcium  Phosphate,  Ca3(P04)2. — 
Amorphous. 

Magnesium  Phosphate.  —  Long 
rhombic  tablets,  which  are  dis- 
solved at  the  edges  by  ammonium 
carbonate  solution,  unlike  triple 
phosphate.  All  the  above  are 
soluble  in  acetic  acid  without 
effervescence. 

Calcium  Carbonate. — Small 
spherical  or  dumb  -  bell  -  shaped 
bodies  soluble  in  acetic  acid  with 
effervescence. 

Ammonium  Urate. — Dark  balls, 
often  covered  with  spines.  Soluble 
in  acetic  or  hydrochloric  acid, 
with  formation  of  uric  acid  crys- 
tals (Fig.  182,  p.  473). 

4.  Specific  gravity. 

5.  Quantity  of  urine  in  twenty-four  hours.  If  the  quantity  is 
abnormally  large  and  the  specific  gravity  high,  test  for  sugar. 

6.  Inorganic  constituents  not  generally  of  clinical  importance,  but 
in  special  diseases  they  should  be  examined — e.g.,  chlorides  in  pneu- 
monia. 

7.  Normal  organic  constituents.  Sometimes  quantitative  estima- 
tion of  urea  or  total  nitrogen  in  fever,  and  in  diabetes  and  Bright's 
disease. 

8.  Chemical  examination  for  abnormal  organic  constituents,  especi- 
ally albumin  and  sugar. 

Albumin. — (i)  Heat  to  boiling  some  of  the  urine  in  a  test-tube.  A 
precipitate  insoluble  on  addition  of  a  f-w  drops  of  acetic  acid  consists 
of  coagulable  protein.  A  precipitate  soluble  in  acetic  acid  consists  of 
earthy  phosphates. 

(2)  Heller's  test.  Put  some  strong  nitric  acid  in  a  test-tube  and 
run  on  to  it  some  urine.     A  white  ring  indicates  protein. 

A  quantitative  estimation  may  be  made  by  the  method  of  Roberts 
and  Stolnikow  or  Esbach  (p.  517). 

Sugar. — (i)  Trommer's  test.  (Fehling's  solution  may  be  used.)  If 
the  result  is  indecisive — 

(2)  Phenyl-hydrazine  test  (p.  518). 

(3)  In  case  of  doubt  confirm  by  yeast  test. 

A  quantitative  estimation  may  be  made  with  Fehling's  solution  or 
the  polarimeter. 


CHAPTER  X 

METABOLISM,  NUTRItlON  AND  DIETETICS 

We  return  now  to  the  products  of  digestion  as  they  are  absorbed 
from  the  alimentary  canal,  and,  still  assuming  a  typical  diet  con- 
taining carbo-hydrates,  fats,  and  proteins,  we  have  to  ask,  What 
is  the  fate  of  each  of  these  classes  of  proximate  principles  in  the 
body  ?  what  does  each  contribute  to  the  ensemble  of  vital  activity  ? 
It  will  be  best,  first  of  all,  to  give  to  these  questions  what  roughly 
qualitative  answer  is  possible,  then  to  look  at  metabolism  in  its 
quantitative  relations,  and  lastly  to  focus  our  information  upon 
some  of  the  practical  problems  of  dietetics. 

Section  I. — Metabolism  of  Carbo-Hydrates — Glycogen. 

The  carbo-hydrates  of  the  food,  passing  into  the  blood  of  the 
portal  vein  in  the  form  of  dextrose,  are  in  part  arrested  in  the  liver, 
and  stored  up  as  glycogen  in  the  hepatic  cells,  to  be  gradually  given 
out  again  as  sugar  in  the  intervals  of  digestion.  The  proof  of  this 
statement  is  as  follows : 

Sugar  is  arrested  in  the  liver,  for  during  digestion,  especially  of  a 
meal  rich  in  carbo-hydrates,  the  blood  of  the  portal  contains  more 
sugar  than  that  of  the  hepatic  vein.  Popielski,  on  the  basis  of 
experiments  in  which  he  fed  with  known  quantities  of  sugar  dogs 
whose  inferior  vena  cava  and  portal  vein  had  been  united  by  an 
Eck's  fistula,  and  determined  the  amount  of  sugar  which  passed 
into  the  urine,  estimates  the  quantity  of  sugar  kept  back  by  the 
liver  at  from  12  to  20  per  cent,  of  the  whole.  In  the  liver  there 
exists  a  store  of  sugar-producing  material  from  which  sugar  is 
gradually  given  off  to  the  blood,  for  in  t4ie  intervals  of  digestion  the 
blood  of  the  hepatic  veins  contains  more  dextrose  (2  parts  per  1,000) 
than  the  mixed  blood  of  the  body  or  than  that  of  the  portal  vein 
(about  I  part  per  1,000).  When  the  circulation  through  the  liver 
is  cut  off  in  the  goose,  the  blood  rapidly  becomes  free,  or  nearly  free, 
from  sugar  (Minkowski).  And  a  similar  result  follows  such  inter- 
ference with  the  hepatic  circulation  as  is  caused  by  the  ligation  of 
the  three  chief  arteries  of  the  intestine  in  the  dog,  even  when  the 

5^5 


526  METABOLISM,  NUTRITION  AND  DIETETICS 

animal  has  been  previously  made  diabetic  by  excision  of  the  pancreas 
(p.  622). 

The  nature  of  the  sugar-forming  substance  is  made  clear  by  the 
following  experiments:  (i)  A  rabbit  after  a  large  carbo-hydrate 
meal,  of  carrots  for  instance,  is  killed  and  its  liver  rapidly  excised, 
cut  into  small  pieces,  and  thrown  into  acidulated  boiling  water. 
After  being  boiled  for  a  few  minutes,  the  pieces  of  liver  are  rubbed 
up  in  a  mortar  and  again  boiled  in  the  same  water.  The  opalescent 
aqueous  extract  is  filtered  off  from  the  coagulated  proteins.  No 
sugar,  or  only  traces  of  it,  are  found  in  this  extract;  but  another 
carbo-hydrate,  glycogen,  a  polysaccharide  giving  a  port-wine 
colour  with  iodine  and  capable  of  ready  conversion  into  sugar  by 
amylolytic  ferments,  is  present  in  large  amount.  (See  Practical 
Exercises,  p.  689.) 

{2)  The  liver  after  the  death  of  the  animal  is  left  for  a  time  in 
situ,  or,  if  excised,  is  kept  at  a  temperature  of  35°  to  40°  C,  or  for 
a  longer  period  at  a  lower  temperature;  it  is  then  treated  exactly 
as  before,  but  no  glycogen,  or  comparatively  little,  can  now  be 
obtained  from  it,  although  sugar  (dextrose)  is  abundant.  The 
inference  plainly  is  that  after  death  the  hepatic  glycogen  is  con- 
verted into  dextrose  by  some  influence  which  is  restrained  or  de- 
stroyed by  boiling.  This  transformation  might  theoretically  be 
due  to  an  unformed  ferment  or  to  the  direct  action  of  the  liver-cells, 
for  both  unformed  ferments  and  living  tissue  elements  are  destroyed 
at  the  temperature  of  boiling  water.  It  has  been  clearly  shown 
that  the  action  is  brought  about  by  a  diastatic  enzyme,  which  some 
writers  call  glycogenase,  for  it  readily  occurs  when  the  minced  liver 
is  mixed  \\dth  chloroform  water,  and  chloroform  kills  all  living 
tissues.  Although  blood  contains  a  diastase  in  small  amount,  the 
change  does  not  depend  essentially  upon  this,  since  the  glycogen 
also  undergoes  hydrolysis  (glycogenolysis)  to  dextrose  when  all  the 
blood  has  been  washed  out  of  the  organ.  Lymph  also  contains  a 
diastase,  but  there  is  evidence  that  the  post-mortem  glycogenolysis 
is  chiefly  due  to  an  enzyme  contained  in  the  hepatic  cells  (an  endo- 
enzyme)  (Macleod).  The  diastases  in  the  blood  and  lymph  seem 
to  be  '  discards  '  of  the  tissues  which  are  on  the  way  to  destruction 
or  elimination  (Carlson).  The  post-mortem  change  is  to  be  regarded 
as  an  index  of  a  similar  action  which  goes  on  during  life:  sugar  in 
the  intact  body  is  changed  into  glycogen;  glycogen  is  constantly 
being  changed  into  sugar.  There  is  no  reason  to  doubt  that  here, 
too,  the  hydrolysis  is  effected  by  the  endo-enzyme.  It  might  be 
supposed,  indeed,  that  the  adjustment  of  the  two  processes  glyco- 
gonesis  and  glycogenolysis  is  simply  a  matter  of  the  alteration  of 
the  equilibrium  in  a  reversible  reaction  (p.  332),  according  to 
whether  the  dextrose  content  of  the  blood  tends  to  rise  or  fall.  If 
the  concentration  of  dextrose  in  the  blood  is  increased,  more  dex- 


METABOLISM  OF  CARBO-HYDRATES— GLYCOGEN  527 

trose  might  be  expected  to  '  diffuse  '  into  the  hepatic  cells,  whose 
content  of  dextrose  in  proportion  to  glycogen  would  increase  till 
the  equilibrium  was  restored  by  the  conversion  of  the  excess  of 
sugar  into  glycogen.  Contrariwise,  a  diminution  in  the  dextrose 
content  of  the  blood  might  be  expected  to  lead  to  diffusion  of 
dextrose  out  of  the  liver-cells,  and  a  consequent  acceleration  of  the 
hydrolysis  of  the  glycogen.  We  have  already  learnt,  however,  that 
in  physiology — above  all,  perhaps,  in  the  physiology  of  the  glands 
— '  simple  '  explanations  are  usually  suspect.  And  when  we  come  to 
study  those  conditions  in  which,  as  a  consequence  of  the  derange- 
ment of  the  mechanisms  which  regulate  the  carbo-hydrate  metabo- 
lism, sugar  appears  in  the  urine,  it  will  be  seen  that  the  matter  is 
more  complicated.  For  one  thing,  the  nervous  system  seems  to 
take  a  hand  in  the  regulation,  and  where  the  nervous  system  takes 
a  hand  things  are  generally  doing  which  the  experienced  physiologist 
does  not  expect  to  be  simple.  We  may  be  certain,  as  in  the  case  of 
the  intracellular  proteolytic  ferments,  that  the  vital  action  of  the 
hepatic  cells  is  a  most  important  factor  in  controlling  the  rate  of 
production  of  the  ferment,  and  therefore  its  concentration  in  rela- 
tion to  that  of  the  substrate  and  the  rate  at  which  it  works. 

(3)  With  the  microscope,  glycogen,  or  at  least  a  substance  which 
is  very  nearly  akin  to  it,  which  very  readily  yields  it,  and  which 
gives  the  characteristic  port-wine  colour  with  iodine,  can  be  actually 
seen  in  the  liver-cells.  The  liver  of  a  rabbit  or  dog  which  has  been 
fed  on  a  diet  containing  much  carbo-hydrate  is  large,  soft,  and  very 
easily  torn.  Its  large  size  is  due  to  the  loading  of  the  cells  wdth  a 
hyaline  material,  which  gives  the  iodine  reaction  of  glycogen,  and 
is  dissolved  out  by  water,  leaving  empty  spaces  in  a  network  of  cell- 
substance.  If  the  animal,  after  a  period  of  starvation,  has  been 
fed  on  protein  alone,  less  glycogen  is  found  in  the  shrunken  liver- 
cells;  if  the  diet  has  been  wholly  fatty,  little  or  no  glycogen  at  all 
may  be  found,  (jlycogen  can  even  be  formed  by  an  excised  liver 
when  blood  containing  dextrose  is  circulated  through  it. 

Formation  of  Glycogen  from  Protein. — In  the  liver-cells  of  the 
frog  in  winter-time  a  great  deal  of  this  hyaline  material — this 
glycogen,  or  perhaps  loose  glycogen  compound — is  present;  in 
summer,  much  less.  The  difference  is  remarkable  if  we  con- 
sider that  in  winter  frogs  have  no  food  for  months,  while  summer 
is  their  feeding-time;  and  at  first  it  seems  inconsistent  with  the 
doctrine  that  the  hepatic  glycogen  is  a  store  laid  up  from  surplus 
sugar,  which  might  otherwise  be  swept  into  the  general  circulation 
and  excreted  by  the  kidneys.  It  has  been  found,  however,  that 
the  quantity  of  glycogen  is  greatest  in  autumn  at  the  beginning  of 
the  winter-sleep,  and  slowly  diminishes  as  the  winter  passes  on, 
to  fall  abruptly  with  the  renewal  of  the  activity  of  the  animal  in 
the  spring.     The  glycogen  present  at  any  moment  is,  therefore. 


528  METABOLISM,  NUTRITION  AND  DIETETICS 

believed  to  be  a  residue,  which  represents  the  excess  of  glycogen 
formed  over  glycogen  used  up;  and  the  amount  is  larger  in  winter, 
not  because  more  is  manufactured  than  in  summer,  but  because 
less  is  consumed.  It  is  possible,  indeed,  to  produce  the  '  summer  ' 
condition  of  the  hepatic  cells  merely  by  raising  the  temperature  of 
the  air  in  which  a  winter  -frog  lives;  at  20°  or  25°  C.  glycogen  dis- 
appears from  its  liver.  Conversely,  if  a  summer  frog  is  artificially 
cooled,  a  certain  amount  of  glycogen  accumulates  in  the  liver.  The 
meaning  of  this  seems  to  be  that  at  a  low  temperature,  when  the 
wheels  of  life  are  clogged  and  metabolism  is  slow,  some  substance, 
probably  dextrose,  is  produced  in  the  body  from  proteins  in  greater 
amount  than  can  be  used  up,  and  that  the  surplus  is  stored  as 
glycogen;  just  as  in  plants  starch  is  put  by  as  a  reserve  which  can 
be  drawn  upon — which  can  be  converted  into  sugar — when  the 
need  arises.  That  carbo-hydrates  may  be  formed  from  proteins 
(or  their  constituent  amino-acids)  has  been  shown  in  various  ways— 
for  example,  by  feeding  dogs  with  almost  pure  protein  (casein)  after 
the  production  of  permanent  glycosuria  by  removal  of  the  pancreas 
(p.  622).  To  induce  the  animal  to  take  the  casein  it  had  to  be 
mixed  with  a  certain  amount  of  butter,  or  serum,  or  meat  extract. 
The  amount  of  sugar  excreted  was  much  more  than  could  possibly 
have  come  from  the  glycogen  originally  present  in  the  animal's  body, 
computing  it  on  the  most  generous  scale  (41  grammes  per  kilo- 
gramme of  body- weight,  according  to  Pfliiger),  or  from  free  carbo- 
hydrate present  in  traces  in  the  food,  or  as  prosthetic  groups  (p.  2) 
in  the  ingested  protein.  That  the  source  of  the  sugar  was  protein 
and  not  fat  was  indicated  by  the  fact  that  when  the  amount  of 
protein  food  was  increased,  the  dextrose  and  the  nitrogen  excreted 
increased  proportionally  (see  also  p.  530). 

Glycogen-Formers. — As  true  glycogen-formers  in  the  higher 
animals — that  is,  compounds  whose  elements  (particularly  the 
carbon)  actually  enter  into  the  composition  of  the  glycogen  mole- 
cule— may  be  mentioned  such  substances  as  proteins  (including 
gelatin),  the  fermentable  sugars,  and  glycerin.  In  the  case  of 
proteins  it  is,  of  course,  not  the  entire  molecule  which  is  transformed 
bodily  into  glycogen,  but  amino-acids  yielded  by  them,  or  dextrose 
derived  from  the  amino-acids.  The  liver  is  of  itself  capable  of 
dealing  only  with  the  dextrose,  and  not  with  the  amino-acids.  At 
least,  when  the  isolated  liver  (of  the  tortoise)  is  perfused  with 
blood  containing  amino-acids  no  increase  in  the  glycogen  of  the 
liver  occurs.  When  glycerin  is  added  to  the  blood  the  glycogen 
content  of  the  liver  is  very  distinctly  increased.  Glycerin  is  a  tri- 
valent  alcohol  (CgHgOg)  whose  aldehyde,  obtained  from  it  by  gentle 
oxidation,  is  glycerose  (CgHgOg),  a  substance  with  the  typical 
properties  of  a  sugar.  In  the  laboratory  it  has  been  shown  that 
two  molecules  of  glycerose  can  be  combined  to  form  one  molecule  of 


METABOLISM  OF  CARBO-HYDRATES— GLYCOGEN         529 

sugar  of  the  hexose  type  with  six  carbon  atoms  (CeHiaOe)  ■  A  similar 
transformation  is  accomplished  in  the  liver,  and  then  a  number  of 
the  monosaccharide  molecules  (CeHigOg)  are  condensed  with  loss  of 
water  to  form  glycogen.  Thus,  wlCgH^aOg) -«H20=  (CeHioOs)^. 
Since  glycerin  is  a  normal  product  of  the  hydrolysis  of  fats,  the 
possibility  that  the  fats  of  the  food  may  contribute  through  their 
glycerin  component  to  glycogen  formation  must  be  admitted.  The 
monosaccharides  dextrose,  levulose,  and  galactose  gave  a  similar 
result,  while  the  disaccharides  cane-sugar  and  lactose  caused  no 
increase  in  the  glycogen  of  the  perfused  liver,  since  the  liver  contains 
no  ferment  capable  of  splitting  them  into  monosaccharides.  And 
although  the  first  step  in  the  linking  of  the  monosaccharide  mole- 
cules would  seem  to  be  the  formation  of  a  disaccharide  such  as 
maltose,  the  glycogen  molecule  must  apparently  be  built  up  from 
single  '  bricks,'  the  monosaccharides,  and  cannot  be  constructed 
from  bricks  which  are  already  coupled  in  pairs,  the  disaccharides. 
Of  course,  since  the  disaccharides  are  hydrolysed  in  the  digestive 
tube  to  simple  sugars,  they  are  to  be  reckoned  with  the  true  glycogen- 
formers,  for  in  the  intact  body  they  are  presented  to  the  hepatic 
cells  in  the  form  of  monosaccharides.  It  is  probable  that  levulose 
and  galactose  are  first  changed  into  dextrose. 

By  the  action  of  alkalies  such  structurally  related  sugars  can  easily 
be  transformed  into  each  other.  Thus  dextrose  is  an  aldehyde  of  an 
alcohol  with  six  carbon  atoms,  and  levulose  the  corresponding  keto- 
hexose . 

By  oxidizing  the  alcohol  we  get  an  aldehyde  or  a  ketone,  according 
to  whether  a  primary  alcohol  group  (CH2.OH)  or  a  secondary  group 
(CH.OH)  is  oxidized,  with  the  loss  of  two  atoms  of  hydrogen.     The 

aldehyde   is  characterized  by  the  presence  of  the   group  C^"  pj,  the 

ketone  by  the  group  CO.  Both  the  aldehyde  and  the  ketone  arc 
sugars,  and  since  each  contains  six  carbon  atoms,  they  are  both  sugars 
of  the  group  known  as  '  hcxoses.'  Dextrose,  being  not  only  a  hexose 
but  an  aldehyde,  may  be  called  an  '  aldohexose,'  and  levulose,  being 
not  only  a  hexose  but  a  ketone,  a  '  keto hexose.' 

CHo.OH  c/2  CHa.Ofi 

I  1^  I 

CH.OH        CH.OH        CO 
CH.OH        CH.OH        CH.OH 

CH.OH        CH.OH        CH.OH 

I  I  I 

CH.OH        CH.OH        CH.OH 

I  i  I 

CH2.OH        CHg.OH        CH2.OH 

6-valent  alcohol.  Aldehyde.  Ketone. 

That  levulose  can  be  changed  into  dextrose  in  the  body  is  indi- 
cated by  the  observation  that  after  extirpation  of  the  pancreas  in 

34 


530  METABOLISM.  NUTRITION  AND  DIETETICS 

dogs  the  administration  of  levulose  is  followed  by  an  increase  in 
the  excretion  of  dextrose  nearly  equal  to  the  amount  of  levulose 
ingested.  It  is  also  stated  that,  when  the  surviving  hver  of  a 
normal  dog  is  perfused  with  a  suspension  of  washed  blood-corpuscles 
to  which  levulose  has  been  added,  dextrose  accumulates  in  the  blood 
and  levulose  disappears  from  it. 

It  has  not  hitherto  been  proved  that  the  fatty  acid  component  of 
the  food  fats  can  be  converted  into  glycogen.  But  a  fatty  acid, 
propionic  acid,  is  capable  of  complete  transformation  into  dextrose 
when  given  either  by  the  mouth  or  subcutaneously  to  dogs  under 
the  influence  of  phlorhizin  (Ringer).  Many  other  bodies  are  known 
to  influence  the  formation  of  glycogen  by  '  sparing  '  substances 
which  are  true  glycogen-producers,  but  their  carbon  does  not  actu- 
ally take  its  place  in  the  glycogen  molecule.  It  has  been  shown  that 
proteins  can  directly  form  glycogen  or  sugar  apart  from  carbo- 
hydrate groups  contained  in  the  protein  molecule.  For  the  proteins 
of  meat,  gelatin,  and  casein  are  capable  of  forming  60  per  cent,  of 
their  own  weight  of  dextrose  in  diabetic 
metabolism,  and  even  the  end  products  of 
pancreatic  digestion  of  meat  yield  so  much 
sugar  that  the  greater  part  of  it  must  have 
come  from  the  amino-bodies,  and  not  from  a 
sugar-group  in  the  protein.  When  given  to 
dogs  with  total  phlorhizin  glycosuria  (p.  542), 
gl3/cin  and  alanin  are  completely,  glutamic  and 
aspartic  acids  in  great  part  (corresponding  to 
""  riaceuta  "containing  ^bout  three  carbon  atoms  of  their  respective 
Glycogen.  molecules),  converted  into  dextrose  (Lusk  and 

Ringer),  and  there  is  no  reason  to  doubt 
that  when  such  substances  are  produced  by  hydrolysis  of  protein 
in  the  normal  body,  and  are  not  all  utilized  in  rebuilding  the  bio- 
plasm, a  portion  of  the  surplus,  after  deamidization,  can  be  trans- 
formed into  glycogen. 

Extra-Hepatic  Glycogen. — While  the  liver  in  the  adult  (containing 
as  it  does  from  2  to  10  per  cent,  of  glycogen,  or  even,  with  a  diet 
rich  in  sugar  or  starch,  more  than  18  per  cent.)  may  be  looked 
upon  as  the  main  storehouse  of  surplus  carbo-hydrate,  depots  of 
glycogen  are  formed,  both  in  adult  and  foetal  life,  in  other  situations 
where  the  strain  of  function  or  of  growth  is  exceptionally  heavy — 
in  the  muscles  of  the  adult  (03  to  0-5  per  cent,  of  the  moist  skeletal 
muscle,  or  on  a  carbo-hydrate  regimen  0.7  to  3.7  per  cent.),  in  the 
placenta,  in  many  developing  organs  in  the  embryo  (muscles,  lungs, 
epithelium  of  the  trachea,  oesophagus,  intestine,  ureter,  pelvis  of 
kidney,  and  renal  tubules).  The  foetus,  however,  is  not,  compared 
with  the  adult,  especially  rich  in  glycogen."  In  the  adult  under 
favourable  circumstances  the  absolute  amount  of  glycogen  in  the 


METABOLISM  OF  CARBO-HYDRATES—GLYCOGEN  531 

muscles  may  be  several  times  greater  than  that  in  the  liver,  and 
usually  the  hepatic  glycogen  makes  up  considerably  less  than  half 
the  total  glycogen  of  the  body.  That  the  muscles  do  not  derive 
their  glycogen  by  the  migration  of  hepatic  glycogen,  but  can  them- 
selves form  it  from  dextrose,  has  been  shown  by  injecting  that  sugar 
subcutaneously  into  frogs  after  excision  of  the  liver.  The  muscle 
glycogen  was  found  to  be  increased. 

Function  and  Fate  of  the  Glycogen. — The  glycogen  store  of  the 
hver  fulfils  a  different  function  from  that  of  the  muscles.  This  is 
indicated  by  the  fact  that  when  dogs,  after  being  put  on  a  given  diet 
for  two  or  three  days,  are  starved  for  a  time,  and  then  put  again  on 
the  original  diet,  the  hepatic  and  the  muscular  glycogen  behave 
differently  at  first  during  the  period  of  re-alimentation.  While 
glycogen  accumulates  in  the  liver  in  greater  quantity  than  under 
normal  conditions  of  nutrition,  in  the  mu  cles  it  at  first  accumulates 
much  less  rapidl}'  than  normally.  This  is  entirely  in  accordance 
with  the  view  that  the  hepatic  glycogen  store  has  for  its  great  func- 
tion the  regulation  of  the  sugar  content  of  the  blood  in  the  interest 
of  all  the  tissues,  while  the  glycogen  store  of  the  muscles  and  other 
tissues  is  mainly  in  the  interest  of  their  own  nutrition  and  a  source 
of  energy  for  their  own  work.  This  does  not  imply  that,  when  sugar 
is  being  absorbed  in  quantities  too  great  for  the  liver  to  deal  with 
after  the  current  needs  of  the  tissues  have  been  satisfied,  they  do 
not  add  to  their  glycogen  reserves.  There  is  every  reason  to  suppose 
that  they  do  so,  and  thus  act  as  a  subsidiary  regulating  mechanism, 
although  a  less  elastic  one  than  that  supplied  by  the  liver.  A  third 
way  in  which  a  portion  of  the  surplus  sugar  can  be  stored  is  in  the 
form  of  fat. 

When  a  fasting  dog  is  made  to  do  severe  muscular  work,  the 
greater  part  of  the  glycogen  soon  disappears  from  its  liver.  When 
a  dog  is  starved,  but  allowed  to  remain  at  rest,  the  glycogen  still 
markedly  diminishes,  although  it  takes  a  longer  time;  and  at  a 
period  when  there  is  still  plenty  of  fat  in  the  body,  there  may  be 
only  a  trace  of  hepatic  glycogen  left.  The  glycogen  which  is  usually 
contained  in  the  skeletal  muscles  also  diminishes  very  rapidly  in  the 
first  days  of  hunger,  but  the  heart  contains  the  normal  amount  of 
glycogen  at  a  time  when  the  proportion  in  the  skeletal  muscles  has 
sunk  to  ^  to  ^ij  of  the  normal. 

These  facts  have  been  taken  to  indicate  that  glycogen  and  the  sugar 
formed  from  it  are  the  readiest  resources  of  the  starving  and  working 
organism,  for  the  transformation  of  chemical  cnerg}^  into  heat  and 
mechanical  work.  To  borrow  a  financial  simile,  tlie  fat  of  the  body 
has  sometimes  been  compared  to  a  good,  but  rather  inactive  security, 
which  can  only  be  gradually  realized;  its  organ-proteins  to  long-date 
bills,  which  will  be  discounted  sparingly  and  almost  with  a  grudge; 
its  glycogen,  its  carbo-hydrate  reserves,  to  consols,  which  can  be  tumcd 
into  money  at  an  hour's  warning.     Glycogen,  on  this  view,  is  especially 


532  METABOLISM.  NUTRITION  AND  DIETETICS 

drawn  upon  for  a  sudden  demand,  fat  for  a  steady  drain,  tissue -protein 
for  a  life-and-death  struggle.  While  there  may  be  some  such  difterence 
in  the  tenacity  with  which  the  different  kinds  of  reserve  material  are 
held  back  from  consumption  when  the  floating  supplies  are  wearing 
low,  modern  investigation  tends  to  the  conclusion  that  the  interchange- 
ability  of  the  various  groups  of  nutritive  substances  is  greater  than 
had  been  supposed,  and  that  in  the  long-run  the  cells — in  normal  cir- 
cumstances at  least — ^never  work  without  dextrose,  even  after  the 
glycogen  store  has  been  practically  all  consumed,  but  secure  it  from 
other  sources. 

Pavy  has  put  forward  the  heterodox  view  that  the  glycogen  formed 
in  the  liver  from  the  sugar  of  the  portal  blood  is  never  reconverted 
into  sugar  under  normal  conditions,  but  is  changed  into  some  other 
substance  or  substances,  and  he  denies  that  the  post-mortem  formation 
of  sugar  in  the  hepatic  tissue  is  a  true  picture  of  what  takes  place 
during  life.  But  in  spite  of  the  brilliant  manner  in  which  he  has 
defended  this  thesis,  both  by  argument  and  by  experiment,  it  must  be 
said  that  the  older  doctrine  of  Bernard,  which  in  the  main  we  have 
followed  above ,  is  attested  by  such  a  cloud  of  modem  witnesses  that  it 
seems  to  be  firmly  and  finally  established. 

Fate  of  the  Sugar — Glycolysis. — ^What,  now,  is  the  fate  of  the 
sugar  which  either  passes  right  through  the  portal  circulation  from 
the  intestine  without  undergoing  any  change  in  the  liver,  or  is 
gradually  produced  from  the  hepatic  glycogen  ?  When  the  pro- 
portion of  sugar  in  the  blood  rises  above  a  certain  low  limit  (about 
1-5  or  2  parts  per  1,000),  some  of  it  is  excreted  by  the  kidneys 
(Practical  Exercises,  p.  691). 

A  large  meal  of  carbo-hydrates  is  frequently  followed  by  a 
temporary  glycosuria,  but  much  depends  upon  the  form  in  which 
the  sugar-forming  material  is  taken.  We  have  seen  that  poly- 
saccharides are  quite  incapable  of  absorption  as  such,  and  that  they 
must  be  very  completely  hydrolysed  in  the  lumen  of  the  alimentary 
canal  before  their  constituent  sugars  have  any  chance  of  reaching  the 
blood.  It  is  therefore  not  to  be  expected  that  the  rapid  absorption 
of  such  considerable  quantities  of  sugar  as  would  lead  to  its  excretion 
should  easily  occur  when  the  carbo-hydrate  is  in  this  form.  Miura 
for  example,  after  an  enormous  meal  of  rice  (equivalent  to  64 
grammes  of  ash-  and  water-free  starch  per  kilo  of  body- weight), 
which,  as  he  mentions,  tasked  even  his  Japanese  powers  of  digestion 
for  such  food  to  dispose  of,  found  not  a  trace  of  sugar  in  the  urine. 
Dextrose,  cane-sugar  and  lactose,  on  the  other  hand,  when  taken  in 
large  amount,  were  in  part  excreted  by  the  kidneys,  as  was  also 
the  case  with  levulose  and  maltose  in  a  dog  (Practical  Exercises, 
p.  690).*    The  amount  of  any  carbo-hydrate  which  can  be  eaten 

*  Twenty-four  healthy  students,  whose  urine  had  previously  been  shown 
to  be  free  from  sugar,  ate  quantities  of  cane-sugar  varying  from  250  grammes 
to  750  grammes.  The  urine  was  collected  in  separate  portions  for  twelve 
to  twenty-four  hours  after  the  meal.  In  only  three  cases  was  reducing  sugar 
found  in  the  urine  (by  Fehling's  and  the  phenyl-hydrazine  test),  and  then 
merely  in  traces.  In  eight  cases  cane-sugar  was  found,  and  estimated  by  the 
polarimeter,  and,  after  boiling  with  hydrochloric  acid,  by  Fehling's  solution. 


METABOLISM  OF  CARBO-H\  DRATES  533 

without  the  appearance  of  sugar  in  the  urine  is  sometimes  called  the 
assimilation  limit  for  that  carbohydrate.  The  attCimpt  has  been 
made  to  fix  the  limit  of  tolerance  of  dextrose  for  normal  persons 
and  persons  suffering  from  incipient  diabetes,  with  the  object  of 
aiding  in  early  diagnosis  of  that  condition.  But  the  limit  varies  with 
so  many  conditions,  only  some  of  which  can  be  controlled,  that  such 
observations  are  not  easily  interpreted. 

Except  as  an  occasional  phenomenon,  glycosuria  other  than  ali- 
mentary is  inconsistent  with  health;  and  therefore  in  the  normal 
body  the  sugar  of  the  blood  must  be  either  destroyed  or  transformed 
into  some  more  or  less  permanent  constituent  of  the  tissues.  The 
transformation  of  sugar  into  fat  we  have  already  mentioned,  and 
shall  have  again  to  discuss;  it  only  takes  place  under  certain  con- 
ditions of  diet,  and  no  more  than  a  small  proportion  of  the  sugar 
which  disappears  from  the  body  in  twenty-four  hours  can  ever,  in 
the  most  favourable  circumstances,  be  converted  into  fat.  The 
dextrose  which  is  taken  up  from  the  blood  by  the  tissues  and  there 
condensed  to  glycogen  suffers  sooner  or  later  the  converse  change, 
in  all  probability  under  the  influence  of  diastases  or  glycogenases 
produced  in  the  cells,  and  reappears  as  dextrose  to  take  its  place 
in  the  cellular  katabolism  and  begin  the  series  of  cleavages  and 
oxidations  by  which  its  chemical  energy  is  set  free.  Accordingly, 
it  is  the  destruction  of  sugar  which  concerns  us  here,  and  there  is 
every  reason  to  believe  that  this  takes  place,  not  in  any  particular 
organ,  but  in  all  active  tissues,  especially  in  the  muscles,  and  to  a 
less  extent  in  glands. 

It  has  been  asserted  that  the  blood  which  leaves  even  a  resting 
muscle,  or  an  inactive  salivary  gland,  is  poorer  in  sugar  than  that 
coming  to  it ;  and  the  conclusion  has  been  drawn  that  in  the  metabo- 
lism of  resting  muscle  and  gland  sugar  is  oxidized,  the  carbon 
passing  off  as  carbon  dioxide  in  the  venous  blood.  This  is  indeed 
extremely  likely,  for  we  know  that,  when  the  skeletal  muscles  of  a 
rabbit  or  guinea-pig  are  cut  off  from  the  central  nervous  system  by 
curara,  the  production  of  carbon  dioxide  falls  much  below  that  of 
an  intact  animal  at  rest ;  and  the  carbon  given  off  by  such  an  animal 
on  its  ordinary  vegetable  diet  can  be  shown,  by  a  comparison  of 
the  chemical  composition  of  the  food  and  the  excreta,  to  come 
largely  from  carbo-hydrates.  But,  considering  the  relatively  feeble 
metabolism  of  muscles  and  glands  when  not  functionally  excited, 
the  large  volume  of  blood  which  passes  through  them,  the  difficulty 
of  determining  small  differences  in  the  proportion  of  sugar  in  such 
a  liquid,  the  possibility  that  even  in  the  blood  itself  sugcu:  may  be 

The  greatest  quantity  of  cane-sugar  recovered  from  the  urine  was  8  grammes 
(7-92  grammes  by  Fehling's  method  and  8-29  grammes  by  the  polarimeter) ; 
the  highest  proportion  of  the  quantity  taken  which  appeared  in  the  urine  was 
2'3  per  cent.  When  dextrose  was  found,  cane-sugar  was  always  present  as 
well. 


534  METABOLISM,  NUTRITION  AND  DIETETICS 

destroyed,  or  that  it  may  pass  from  the  blood,  without  being  oxi- 
dized, into  the  lymph,  too  much  weight  may  be  easily  given  to  the 
results  of  direct  analysis  of  the  in-coming  and  out-going  blood. 
And  although  the  results  of  Chauveau  and  Kaufmann,  obtained  in 
this  way,  fit  in  fairly  well  with  what  we  have  already  learnt  by  less 
direct,  but  more  trustworthy,  methods,  such  as  the  study  of  the 
respiratory  exchange,  they  cannot  be  accepted  as  yielding  exact 
quantitative  information.  They  found  that  in  one  of  the  muscles 
of  the  upper  lip  of  the  horse  the  quantity  of  dextrose  used  up  during 
activity  (feeding  movements)  was  3-5  times  as  much  as  in  the  same 
muscle  at  rest,  and  this  corresponded  with  the  deficit  of  oxygen  in 
the  blood  entering  the  muscle,  and  with  the  excess  of  carbon  dioxide 
in  the  blood  leaving  it.  More  dextrose  was  also  destroyed  in  the 
active  than  in  the  passive  parotid  gland  of  the  horse,  but  the  excess 
per  unit  of  weight  of  the  organ  was  far  less  than  in  muscle.  In  dogs 
whose  abdominal  viscera  have  been  removed,  so  that  they  constitute 
practically  preparations  composed  of  skeletal  muscles  it  has  been 
found  that  the  amount  of  dextrose  which  disappears  from  100  grammes 
of  blood  per  minute  varies  from  o  47  to  i  -8  milligrammes,  the  irregu- 
larities probably  depending  largely  upon  the  irregular  consumption 
by  the  muscles  of  the  glycogen  stored  in  them  (Macleod  and 
Pearce). 

Intermediary  Metabolism  of  Carbo- Hydrates. — Concerning  the  pro- 
cesses and  the  stages  by  which  dextrose  is  destroyed  in  the  tissues, 
we  have  no  very  exact  information,  and  it  cannot  be  definitely  stated 
at  present  what  share  is  taken  by  cleavage  and  what  by  oxidation, 
or  rather  through  what  intermediate  products,  formed,  it  may  be, 
now  by  simple  cleavage,  now  by  oxidation,  again  by  a  combination 
of  cleavage  and  oxidation,  the  dextrose  molecule  is  finally  resolved 
into  carbon  dioxide  and  water.  It  must  be  remembered  that  the 
synthetic  powers  of  animal  cells  are  now  known  to  be  very  extensive. 
They  build  carbo-hydrates,  fats,  phosphatides,  and  proteins,  as 
well  as  destroy  them,  and  at  any  of  the  earlier  stages  at  any  rate 
the  degradation  products  of  dextrose,  or  some  of  them,  may  be 
utilized  in  the  construction  of  new  compounds — for  example,  of  fat — 
either  in  the  cells  where  they  arise  or  elsewhere  in  the  body.  In 
like  manner  the  decomposition  of  a  molecule  of  dextrose  begun  in 
one  cell  or  in  one  tissue  may  be  consummated  in  another  to  which 
intermediate  products  are  conveyed  in  the  blood.  In  such  ways 
it  is  obvious  that  the  katabolic  processes  may  be  finely  regulated 
both  qualitatively  and  quantitatively  in  accordance  with  the 
specific  wants  of  different  organs  and  the  intensity  of  their  func- 
tional activity  from  time  to  time.  It  must  be  said,  however,  that 
at  present  there  are  few  definitely  ascertained  facts  to  guide  us  in 
trjdng  to  form  a  scheme  of  the  actual  changes  which  occur  in  the 
intermediate  kataboUsm  of  carbo-hydrates,  and  the  sequence  which 


METABOLISM  OF  CARBO-HYDRATES 


535 


H— C— OH 
1 

H— C— OH 

1 

Oil— C— H 
1 

OH— C— H 

H— C— OH 

1 

H— C— OH 

H— C— OH 
1 

H— C— OH 

1 

CH2OH 

CH2OH 

d-dextrose. 

d-glyconic  acid. 

they  normally  follow.  Glycuronic  acid  has  been  previously  men- 
tioned as  a  substance  occurring  even  in  normal  urine  in  small 
amount.  It  is  very  closely  related  to  dextrose,  as  a  comparison  of 
their  constitutional  formulae  shows: 

COH  COOH  COH 

I  I  I 

H— CO— H 

I 
OH— C— H 

1 
H— C— OH 

I 
H— C— OH 

I 
COOH 

«i-glycuronic  acid. 

Glycuronic  acid  agrees  with  dextrose  in  containing  the  character- 
istic aldehyde  group  C^^tt,  but  differs  in  that  by  oxidation  two 

atoms  of  hydrogen  in  the  primary  alcohol  group  CHgOH  have  been 
replaced  by  one  atom  of  oxygen.  There  is  reason  to  believe  that 
in  the  tissues  glycuronic  acid  can  be  formed  from  dextrose  in  the 
same  way,  possibly  through  the  mediation  of  an  enzyme,  and  it 
may  therefore  represent  a  stage  in  the  katabolism  of  sugar.  But 
it  is  not  known  whether  this  is  a  normal  transformation  through 
which  the  whole  or  the  greater  part  of  the  dextrose  passes,  or  only 
a  transformation  involving  a  small  part  of  the  sugar  under  normal 
conditions.  The  appearance  in  the  urine  of  large  quantities  of 
glycuronic  acid,  paired  as  already  explained  with  various  com- 
pounds, in  certain  pathological  states  or  after  the  administration 
of  certain  drugs  (p.  476),  might  be  explained  either  as  the  result  of 
an  increased  production  of  that  substance  through  a  deflection  of  the 
normal  trend  of  carbo-hydrate  degradation,  or  as  the  result  of  a  failure 
on  the  part  of  the  cells  to  further  transform  the  glycuronic  acid  in 
the  quantities  normally  produced. 

Lactic  acid  is  the  one  intermediate  stage  in  the  decomposition  of 
dextrose  in  the  tissues  whose  importance  seems  to  be  definitely 
ascertained.  The  muscles  and  the  liver  have  been  proved  to  possess 
the  power  of  producing  lactic  acid  from  dextrose  obtained  directly 
from  the  blood  or  from  the  hydrolysis  of  their  own  store  of  glycogen, 
and  there  is  little  doubt  that  this  power  is  shared  by  many,  perhaps 
by  all,  of  the  other  organs.  There  is  also  good  evidence  that  the 
lactic  acid  thus  formed  can  be,  and  under  normal  conditions  is,  in 
large  part  oxidized  so  as  eventually  to  yield  carbon  dioxide  and 
water,  although  there  is  reason  to  believe  that  a  portion  of  it  may 
be  utilized  for  the  synthesis  of  more  complex  bodies. 

The  chemistry  of  the  change  or  series  of  changes  by  which  lactic 
acid  is  produced  from  dextrose  and  the  end-products,  carbon  dioxide 


^ 


530 


METABOLISM.  NUTRITION  AND  DIETETICS 


and  water,  from  lactic  acid  has  given  rise  to  much  discussion,  and  is 
not  yet  clearly  knowTi-.  The  following  scheme,  based  on  the  researches 
of  Embden  and  others,  and  quoted  from  Abderhalden,  illustrates  one 
suggestion  as  to  the  course  of  the  series  of  transformations,  although 
it  must  be  taken  only  as  a  diagram  of  the  sequence  of  some  of  the 
possible  stages.  A  molecule  of  dextrose  is  represented  as  giving  rise 
to  two  molecules  of  glyceric  aldehyde,  each  of  which  then  5-ields  a  mole- 
cule of  lactic  acid.  Each  molecule  of  lactic  acid,  losing  two  atoms  of 
hydrogen,  becomes  converted  into  a  molecule  of  pyruvic  acid,  which 
by  the  loss  of  the  elements  constituting  a  molecule  of  carbon  dioxide 
becomes  acetaldehyde  or  acetic  aldehyde,  and  this  by  oxidation  acetic 
acid,  which  is  then  oxidized  to  carbon  dioxide  and  water.     Thus — 


,\H 
H— C— OH 

HO— C— H 

I 
H— C— OH 

I 
H— C— OH 

I 
CHgOH 

d-dextrose. 


COOH 


c^o 

[\H 
H— C— OH 


\ 


--^ 


CH2OH 

|\H 
H— C— OH 


CH2OH 

2  molecules 
glyceric  aldehyde. 


COOH 

H— C— OH    -H2     -> 

I 
CH, 


d-\3,ct\c  acid. 


.H 


COOH 


CO        -CO.,  -> 


+  0 


+  4O 


CH3 

Pyruvic  acid. 


CH, 


Acetaldehyde. 


CH3 

Acetic  acid. 


2CO2 

2H2O 

Carbon  dioxide 
and  water. 


It  has  been  shown  that  acetaldehyde  and  carbon  dioxide  are  formed 
from  pyruvic  acid  by  the  action  of  a  ferment  contained  in  yeast, , and 
there  is  some  evidence  that  a  similar  transformation  may  occur  in  the 
liver. 

It  is  to  be  particularly  remarked  that  according  to  this  scheme 
the  whole  of  the  dextrose  molecule  is  still  represented  in  the  lactic 
acid  formed  from  it.  Up  to  this  stage  no  part  of  the  molecule  has 
been  burnt.  Nearly  the  whole  of  the  chemical  energy — i.e.,  all  but 
about  3  per  cent,  of  it — is  still  available.  For  a  gramme  of  lactic 
acid  yields  3,661,  and  a  gramme  of  dextrose  3,762,  small  calories  on 
complete  combustion.  The  intermediate  products  of  the  decom- 
position may  therefore  be  transported  from  the  place  of  origin  and 
utilized  elsewhere  with  scarcely  any  loss  of  energy.  Further,  it  is 
'indicated  in  the  scheme  that  the  degradation  process  is  not  merely 
a  series  of  cleavages  and  oxidations,  but  that  these  may  be  inter- 
spersed with  stages  of  reduction.  It  is  also  clearly  suggested  that 
at  certain  points  the  metabolism  may  become  recessive  and  syn- 


METABOLISM  OF  CARBO-HYDRATES 


537 


theses  be  started,  which  may  go  far  to  retrace  the  steps  of  the  pre- 
ceding katabolism  in  respect  to  a  portion  of  the  dextrose. 

Thus,  lactic  acid  can  be  rctransformed  into  dextrose,  and  this,  of 
course,  into  glycogen.  The  formation  of  fat  from  sugar  may  also 
start  from  some  of  the  stages  displayed  in  the  scheme,  for  it  is 
only  a  short  step  to  obtain  by  the  reduction  of  glyceric  aldehyde  its 
alcohol  glycerin.  And  from  acetaldehyde  fatty  acids  can  be 
derived. 

Not  only  does  lactic  acid  afford  a  point  of  contact  between  the 
metabolism  of  carbo-hydrates  and  that  of  fats — a  junction,  so  to 
speak,  where  these  two  great  metabolic  currents  cross  each  other, 
and  where  material  originating  in  the  one  may  be  shunted  into  the 
other — but  it  also  affords  a  point  of  junction  and  interchange  with 
the  current  of  protein  metabolism.  For  example,  certain  of  the 
amino-acids,  such  as  alanin,  yield  as  a  decomposition  product  a 
compound  called  methylglyoxal  (CHg.CO.CHO),  which  by  the 
assumption  of  a  molecule  of  water  can  be  changed  into  lactic  acid. 
It  may  also  be  one  of  the  intermediate  stages  in  the  decomposition 
of  dextrose  as  a  precursor  of  lactic  acid,  and  one  of  the  ways  in 
which  the  conversion  of  amino-acids  into  dextrose  is  accomplished 
may  be  through  this  link. 

Pyruvic  acid  is  another  possible  link.  As  has  just  been  mentioned, 
it  probably  forms  a  stage  in  the  decomposition  of  dextrose,  and  has,  in 
addition,  chemical  relations  on  the  one  hand  to  certain  of  the  amino- 
acids,  especially  to  alanin,  and  on  the  other  to  glycerin  and  even  to 
fatty  acids.     Thus — 


Clio  CHo 

I  I 

CH.NH2  +  O   =  CO  -t-NHg 


COOH 

Alanin  (aamlno-pro- 
pionic  acid. 


COOH 

Pyruvic  acid. 


CH2.OH 


CH3 

I 


CH.OH-f-20     =      CO-I-2H2O 
I  I 

CHo.OH  COOH 


Glycerin. 


Pyruvic  acid. 


The  more  completely  the  various  steps  in  the  metabolism  of  the 
three  great  groups  of  food  substances  are  unveiled,  the  more 
clearly  does  it  appear  that,  far  from  being  independent  circuits, 
the  three  currents  are  constantly  exchanging  materials  with  each 
other. 

It  is  to  be  supposed  that  in  many  of  these  transformations  enzymes 
are  concerned,  although  comparatively  little  is  definitely  known  as 
to  this.  Normal  blood  itself  has  been  credited  with  a  ferment 
which  has  the  power  of  destroying  sugar  (glycolysis).  But  with 
rigid  aseptic  precautions  the  loss  of  sugar,  even  in  several  hours,  is 
small,  and  it  is  doubtful  whether  such  a  ferment  exists.  On  the 
other  hand,  Cohnheim  stated  that  while  no  glycolytic  ferment  can 
be  demonstrated  in  the  pancreas,  and  only  an  exceedingly  weak 
glycolytic  action  in  muscular  tissue  (Brunton),  by  combining  ex- 


538  METABOLISM,  NUTRITION  AND  DIETETICS 

tracts  of  pancreas  and  extracts  of  muscles,  distinct  glycolysis,  due 
to  a  ferment  action,  could  be  produced.  He  suggested  that  the 
glycolytic  ferment  is  activated  by  another  substance,  as  trypsinogen 
is  activated  by  enterokinase  (p.  366).  This  announcement  aroused 
great  interest,  since  it  is  known  that  the  pancreas  is  intimately 
concerned  in  the  metabolism  of  sugar.  That  sugar  disappears 
under  the  conditions  of  Cohnheim's  experiments  has  been  confirmed 
by  a  number  of  observers.  But  his  interpretation  of  his  results  has 
not  been  generally  accepted.  According  to  Levene  and  Meyer, 
the  dextrose,  far  from  being  burnt,  seems  to  be  condensed  to  a  poly- 
saccharide, and  can  be  recovered  by  hydrolysing  this  compound 
when  the  mixture  is  acted  on  by  dilute  acid.  The  action  of  the 
pancreas-muscle  mixture  is,  therefore,  not  a  true  glycolysis.  In- 
deed, of  all  the  tissues  investigated  by  Levene,  leucocytes  alone  can 
be  credited  with  a  real  glycolytic  action.  Excision  of  the  pancreas 
in  dogs  causes  permanent  glycosuria  (pancreatic  diabetes)  (v.  Mering 
and  Minkowski),  which  is  prevented  if  a  portion  of  the  pancreas  be 
left  (p.  622).  Diabetes  in  man  is  known  to  be  frequently  associated 
with  pancreatic  lesions.  Although  much  still  remains  obscure,  the 
study  of  this  pathological  form  of  glycosuria  and  of  the  experimental 
glycosurias  has  thrown  light  upon  the  normal  metabolism  of  carbo- 
hydrates and  upon  those  regulative  mechanisms  whose  breakdown 
is  responsible  for  the  excretion  of  sugar.  It  will  be  best  to  discuss 
the  experimental  glycosurias  first,  and  to  begin  with  the  form  which 
probably  is  better  understood  than  any  other,  the  so-called  punc- 
ture glycosuria. 

Puncture  Glycosuria — Sugar-Regulating  Mechanism. — An  arti- 
ficial and  temporary  glycosuria,  in  which  the  sugar  in  the  urine  un- 
doubtedly arises  from  the  hepatic  glycogen,  can  be  caused  by  punc- 
turing the  medulla  oblongata  in  a  rabbit — for  example,  at  a  level 
between  the  origins  of  the  auditory  nerves  and  the  vagi.  It  is  stated 
that  a  puncture  of  the  thalamencephalon,  or  'tween-brain  (p.  822), 
produces  the  same  effect.  If  the  animal  has  been  previously  fed  with 
a  diet  rich  in  carbo-hydrates — that  is,  if  it  has  been  put  under  con- 
ditions in  which  the  liver  contains  much  glycogen — the  quantity  of 
sugar  excreted  by  the  kidneys  will  be  large.  The  immediate  cause 
of  the  glycosuria  is  an  increase  in  the  sugar  content  of  the  blood 
(hyperglycsemia),  an  increase  which  is  most  pronounced  in  the  blood 
of  the  hepatic  vein.  If,  on  the  other  hand,  the  animal  has  been 
starved  before  the  operation,  so  that  the  liver  is  free,  or  almost  free, 
from  glycogen,  the  puncture  will  cause  little  or  no  sugar  to  appear 
in  the  urine,  and  the  proportion  of  sugar  in  the  blood  will  remain 
normal.  That  nervous  influences  are  in  some  way  involved  in  the 
mobilization  of  the  glycogen  reserve  of  the  liver  is  shown  by  the 
absence  of  glycosuria  if  the  splanchnic  nerves,  or  the  spinal  cord 
above  the  third  or  fourth  dorsal  vertebra,  be  cut  before  the  puncture 


METABOLISM  OF  CARBO-HYDRATES— GLYCOSURIAS        539 

is  made.  But  sometimes  these  operations  are  themselves  followed 
by  temporary  glycosuria,  due,  it  is  believed,  to  irritation  of  the 
same  efferent  nervous  path  whose  elimination  when  the  splanchnics 
are  divided  prevents  the  glycosuria.  The  simplest  explanation  of 
the  phenomena  is  that  a  '  sugar  centre  ' — that  is  to  say,  a  centre 
which  has  the  important  office  of  regulating  the  sugar  content  of  the 
blood  by  governing  the  rate  at  which  glycogen  is  built  up  and  de- 
composed in  the  liver,  as  the  salivary  centre  regulates  the  rate  at 
which  the  constituents  of  saliva  are  formed  and  discharged — has 
been  injured  or  irritated  by  the  puncture.  If  a  nervous  centre  does 
in  fact  preside  over  this  internal  secretion  of  the  liver,  it  will,  of 
course,  be  connected  with  efferent  and  afferent  nerves.  The  former, 
as  defined  by  the  experiments  alluded  to,  seem  to  be  confined  to 
the  splanchnic  nerves;  the  latter  are  believed  to  run  especially, 
though  not  exclusively,  in  the  vagus.  Section  of  the  vagi  has  no 
effect  either  in  causing  glycosuria  of  itself  or  in  preventing  the 
'  puncture  '  glycosuria,  but  stimulation  of  the  central  ends  of  these 
and  of  other  afferent  nerves  may  cause  sugar  to  appear  in  the 
urine,  although  not,  it  is  said,  if  precautions  are  taken  to  prevent 
any  degree  of  asphyxia.  Asphyxia  produces  an  increase  in  the 
sugar  content  of  the  blood,  an  increase  in  the  flow  of  urine  and 
glycosuria. 

It  has  usually  been  assumed  that  this  action  of  asphyxia  is  due  to 
the  effect  upon  the  centre  of  blood  over-rich  in  carbon  dioxide  (and 
other  metabolic  products)  or  impoverished  as  regards  oxygen.  But 
there  is  some  evidence  that  the  altered  blood  may  also  affect  the 
liver-cells  directly,  or,  what  comes  to  the  same  thing  in  the  long-run, 
that  interference  with  the  internal  respiration  of  the  hepatic  tissue, 
operating,  it  may  be,  through  an  increase  in  the  concentration  of  the 
hydrogen  ions,  upsets  the  equilibrium  of  those  intracellular  reactions 
by  which  glycogen  is  formed  from  dextrose  and  dextrose  from 
glycogen.  In  like  manner  it  may  be  supposed  that  under  normal 
conditions  the  rate  of  transformation  of  the  hepatic  glycogen  into 
dextrose  is  adjusted  to  the  dextrose  content  of  the  blood,  not  only 
by  reflex  nervous  impulses  passing  through  the  sugar-regulating 
centre,  but  also  by  the  direct  influence  of  the  dextrose  itself  circu- 
lating in  the  blood,  upon  whose  concentration  the  reaction  of  the 
centre  on  the  one  hand  and  of  the  liver-cells  on  the  other  may  in 
part  depend.  So  that  when  the  proportion  of  sugar  in  the  blood 
tends  to  sink  we  may  perhaps  picture  the  centre  as  sending  impulses 
to  the  liver  which  increase  the  rate  at  which  the  glycogen  is  hydro- 
lysed ;  and  when  the  proportion  tends  to  rise,  we  may  think  of  it  as 
sending  impulses  which  inhibit  the  hydrolysis,  both  effects  being 
accentuated  by  the  direct  influence  of  the  changes  of  concen- 
tration on  the  hepatic  cells.  Whatever  the  mechanism  may  be 
through  which  the  puncture  hastens  the  transformation  of  glycogen 


540  METABOLISM.  NUTRITION  AND  DIETETICS 

into  dextrose  in  the  liver,  there  is  evidence  that  the  amount  of  the 
enzyme  which  hydrolyses  the  glycogen  is  increased.  Whether  the 
action  of  the  enzyme  is  favoured  in  some  other  way — e.g.,  by  the 
production  of  a  co-ferment  or  by  some  change  in  the  condition  of 
the  glycogen  which  renders  it  more  open  to  attack— is  unknown. 
Certain  facts  have  recently  been  brought  forward  which  go  to 
show  that  the  action  of  the  splanchnic  fibres  on  the  liver  is  not 
a  direct  action,  but  that  in  some  way  or  other  the  concomitant 
activity  of  the  adrenal  glands  is  essential.  For  if  the  adrenals  have 
been  previously  extirpated,  the  puncture  does  not  cause  glycosuria. 
It  was  at  first  thought  that  the  reason  for  this  was  that  the  removal 
of  the  adrenals  is  itself  followed  by  the  disappearance  of  glycogen 
from  the  fiver,  and,  as  has  been  pointed  out,  the  presence  of  glycogen 
in  the  liver  is  essential  to  the  success  of  the  puncture  experiment. 
The  matter,  however,  is  not  so  simple.  For  although  in  certain 
animals — e.g.,  the  dog — the  liver  does  lose  all  its  glycogen  when  the 
adrenals  have  been  taken  away,  this  is  not  the  case  in  the  rabbit, 
and  yet  in  the  rabbit  also  the  urine  remains  free  from  sugar  after 
puncture  in  the  absence  of  the  adrenal  glands.  In  some  way  or 
other,  then,  the  adrenals  do  intervene  in  the  production  of  puncture 
glycosuria.  The  observation,  which  is  easily  confirmed,  that  the 
injection  of  adrenalin  (or  epinephrin)  (p.  541)  under  the  skin  or  into 
the  blood,  or  into  one  of  the  serous  sacs,  does  cause  a  pronounced 
increase  in  the  sugar  content  of  the  blood,  and  the  appearance  of 
dextrose  in  the  urine,  seemed  at  first  to  supply  the  missing  Hnk  in 
the  chain  of  evidence.  What  could  be  simpler  than  the  assumptic  n 
that  the  splanchnic  fibres  stimulated  in  the  puncture  experiment 
were  fibres  going  not  to  the  fiver,  but  to  the  adrenals,  which  occa- 
sioned an  outpouring  of  adrenalin  into  the  blood,  and  that  puncture 
glycosuria  was  therefore  merely  a  particular  case  of  adrenalin  glyco- 
suria ?  It  is  known  that  excitation  of  the  splanchnic  nerves  causes 
the  passage  of  adrenafin  into  the  blood  of  the  adrenal  veins  (p.  640). 
It  is  known  that  puncture  of  the  medulla  oblongata  diminishes  tl  e 
epinephrin  content  of  the  adrenal  glands.  The  argument  seemed 
straightforward,  and  the  adrenal  hypothesis  of  puncture  glycosuria 
triumphant.  As  soon,  however,  as  the  matter  was  put  to  the  test 
of  quantitative  experiments,  the  hypothesis  began  to  crumble.  It 
was  shown,  for  example,  that  during  a  stimulation  of  the  splanchnic 
nerves  sufficient  to  cause  a  decided  increase  in  the  dextrose  content 
of  the  blood,  a  quantity  of  adrenalin  was  given  off  to  the  adren:  1 
veins,  which,  when  mingled  with  the  rest  of  the  blood  on  its  way 
to  the  liver,  could  not  possibly  amount  to  more  than  one  in  a  hundred 
million  parts  of  blood,  a  concentration  in  which  adrenalin,  when 
introduced  artificially  into  the  blood-stream,  produces  no  glycosuria 
whatever,  nor,  indeed,  any  recognizable  physiological  effect.  Stiil 
more  significant  is  the  fae*"  that,  after  destroying  the  hepatic  plexus, 


METABOLISM  OF  CARBO-HYDRATES— GLYCOSURIAS       541 

stimulation  of  the  splanchnic  nerves  causes  no  increase  in  the  blood- 
sugar  in  spite  of  the  increased  output  of  adrenalin  by  the  way  of  the 
adrenal  veins.  On  the  other  hand,  excitation  of  the  hepatic  plexus 
causes  hyperglycaemia  (Macleod  and  Pearce).  It  is  not,  then,  a 
direct  action  on  the  liver  of  epinephrin  secreted  in  response  to 
stimulation  of  splanchnic  fibres  supplying  the  adrenal  glands  which 
is  responsible  for  the  increase  in  the  dextrose  content  of  the  blood. 
The  adrenals,  however,  play  some  part.  For  in  their  absence 
stimulation  of  the  hepatic  plexus  is  not  followed  by  hyperglycemia. 
But  whether  this  is  due  to  general  derangement  of  the  normal 
carbo-hydrate  metabolism  in  their  absence,  or  to  the  loss  of  some 
special  influence  on  the  liver,  without  which  stimulation  of  the 
hepatic  plexus  is  ineffective,  is  unknown. 

Although  several  of  the  operations  which  lead  to  temporary 
glycosuria  undoubtedly  bring  about  changes  in  the  hepatic  circula- 
tion, it  is  as  yet  impossible  to  say  whether  vaso-motor  effects  con- 
tribute essentially  to  the  result,  or  whether  it  is  due  entirely  to 
nervous  stimulation  of  the  liver-cells,  or  to  withdrawal  of  such 
stimulation  or  control  (see  also  p.  502).  There  is  some  evidence 
that  excitation  of  the  uncut  great  splanchnic  nerve  (on  the  left  side) 
in  dogs  may  cause  hyperglyccemia,  diuresis,  and  glycosuria,  even 
under  conditions  in  which  as  far  as  possible  circulatory  effects  are 
eliminated.  Contrariwise,  when  in  the  puncture  experiment  on  an 
unnarcotized  animal  the  small  instrument  does  not  wound  the 
medulla  oblongata  in  the  right  place,  a  rise  of  blood-pressiire  due 
to  excitation  of  the  vaso-motor  centre  may  occur  without  any 
glycosuria.  But  absolute  proof  of  the  existence  of  glycogenolytic 
nerve  fibres  going  to  the  liver — that  is,  fibres  whose  stimulation 
accelerates  the  hydrolysis  of  glycogen  into  dextrose  (Macleod) — has 
not  yet  been  brought  forward. 

Adrenalin  Glycosuria. — In  adrenalin  glycosuria  the  sugar-content 
of  the  blood  is  increased.  Subcutaneous  injection  of  adrenalin 
chloride  causes  a  mild,  intravenous  injection  a  greater  glycosuria, 
and  intraperitoneal  injection  the  greatest  gljxosuria  of  all  (Herter). 
The  best  evidence  is  that  the  glycosuria  is  produced  by  some  action 
on  the  Hvcr,  possibly  through  the  e.xcitation  of  sympathetic  fibres 
controlling  the  production  of  dextrose  from  glycogen  (Underbill  and 
Closson),  or  by  a  direct  effect  on  the  hepatic  cells,  which  hastens  the 
normal  transformation  of  glycogen  into  dextrose,  or  hinders  the 
normal  transformation  of  dextrose  into  glycogen.  It  has  been 
stated  that  in  the  isolated  survi\ang  liver  of  the  frog  adrenalin  causes 
the  glycogen  to  be  rapidly  converted  into  dextrose.  While  this 
confirms  the  view  that  experimental  adrenalin  glycosuria  is  due  to 
an  action  on  the  liver  which  increases  the  sugar-content  of  the  blood, 
it  does  not  necessarily  show  that  the  action  is  exerted  directly  on 
the  hepatic  cells  without  the  intervention  of  nerve  fibres.     For  the 


542  METABOLISM.  NUTRITION  AND  DIETETICS 

sympathetic  nerve-endings  may  survive  a  considerable  time.  The 
theory  that  epinephrin  causes  glycosuria  by  inhibiting  the  internal 
secretion  of  the  pancreas,  and  that  the  condition  is  therefore  a  par- 
ticular variety  of  pancreatic  diabetes,  is  erroneous.  Adrenahn 
glycosuria  does  not  seem  to  be  in  any  way  related  to  true 
diabetes.  The  complete  metabolism  of  dextrose  is  not  interfered 
with.  Indeed,  a  much  larger  proportion  of  the  total  heat  produced 
comes  from  the  destruction  of  sugar  after  the  subcutaneous  injection 
of  epinephrin  into  dogs  than  in  the  normal  animals  (Lusk  and  Riche). 
If  in  spite  of  this  glycosuria  ensues,  it  is  only  because  the  carbo- 
hydrate reserve  of  the  body  is  mobilized  so  rapidly  that  it  cannot 
possibly  be  all  consumed.  Nor  does  epinephrin  cause  any  increased 
production  of  sugar  from  protein  or  from  fat.  For  in  dogs  rendered 
diabetic  by  phlorhizin  and  freed  from  glycogen  by  shivering,  injec- 
tion of  epinephrin  is  not  followed  by  an  increase  of  either  sugar  or 
nitrogen  in  the  urine  (Ringer).  After  repeated  injections  of  adren- 
alin, a  tolerance  for  it  is  established,  and  glycosuria  is  no  longer 
caused. 

Phlorhizin  Glycosuria,  produced  by  subcutaneous  injection  of  the 
glucoside  phlorhizin,  agrees  with  pancreatic,  but  differs  from  punc- 
ture diabetes  in  this,  that  it  can  be  produced  in  an  animal  free 
from  glycogen,  and  is  accompanied  by  extensive  destruction  of 
proteins.  It  differs  from  other  forms  of  diabetes  in  being  associated, 
not  with  an  increase,  but  with  a  diminution,  in  the  sugar  of  the  blood. 
This  is  best  explained  by  supposing  that  the  phlorhizin  acts  on  the 
kidney  in  such  a  way  as  to  increase  the  permeability  of  the  glomeru- 
lar epithelium  for  sugar,  or  (in  terms  of  the  secretion  theory  of  urine 
formation)  in  such  a  way  as  to  increase  its  sensitiveness  to  the 
stimulus  of  sugar  circulating  in  the  blood.  The  sugar  is  therefore 
rapidly  swept  out  of  the  circulation,  and  this  leads  secondarily  to 
an  increased  production  of  sugar  to  make  good  the  loss.  In  addi- 
tion, within  certain  limits  there  is  a  total  inability  on  the  part  of 
the  body  to  consume  dextrose. 

After  the  preliminary  sweeping  out  of  the  sugar  already  in  the 
body,  a  definite  ratio  is  established  between  the  dextrose  and  the 
nitrogen  eliminated  in  the  urine  (dextrose  :  nitrogen  :  :  3-6or  37  :  i). 
The  sugar  at  this  stage  is  produced  entirely  from  proteins,  and  not 
at  all  from  fat.  It  is  a  fact  of  considerable  interest  that,  if  small 
quantities  of  dextrose  are  now  given,  the  amount  of  protein  de- 
stroyed is  reduced  to  some  extent,  although  all  of  the  dextrose  is 
excreted,  and  none  of  it  is  burnt  (Ringer).  This  supports  the 
hypothesis  of  Landergren  that  in  starvation  some  of  the  protein  is 
metabolized  for  the  formation  of  the  indispensable  dextrose,  and 
that  this  fraction  can  be  '  spared  '  by  carbohydrate,  though  not  by 
fat.  The  protein  metabolized  is  so  much  increased  under  the 
influence  of  phlorhizin  that  it  exceeds  the  starvation  requirement 


METABOLISM  OF  CARBO-HYDRATES— GLYCOSURIAS        543 

by  a  greater  amount  than  in  pancreatic  diabetes,  perhaps  because 
the  diminished  content  of  sugar  in  the  blood  constitutes  a  more 
insistent  call  upon  the  proteins  to  produce  sugar.  In  pancreatic 
diabetes,  where  hyperglyca^mia  exists,  there  can  at  least  be  no 
reason  for  the  formation  of  sugar  from  protein  for  the  maintenance 
of  the  normal  sugar-content  of  the  blood,  and  it  is  interesting  that 
in  this  condition  the  giving  of  dextrose  does  not  seem  to  spare  any 
protein  (p.  595).  The  degree  of  intolerance  for  carbo-hydrates  in 
pathological  diabetes  maj^be  arrived  at  by  putting  the  patient  on 
a  diet  of  protein  and  fatTrich  cream,  meat,  butter,  and  eggs),  and 
determining  the  ratio  of  dextrose  to  nitrogen  excreted.  If  it  is  3.6  or 
37:  I,  intolerance  is  complete,  none  of  the  dextrose  produced  from 
protein  being  burned,  and  there  will  probably  be  a  quickly  fata) 
issue  (Lusk  and  Mandel). 

Glycosuria  can  be  caused  in  many  other  ways  than  those  already 
mentioned.  Sometimes  the  action  seems  to  be  a  direct  one  on  the 
sugar-regulating  centre — e.g.,  in  concussion  of  the  brain,  occlusion 
and  subsequent  release  of  the  arteries  supplying  the  brain  and 
cervical  cord,  and  acute  haemorrhage.  Carbon  monoxide  has  a 
similar  action  owing  to  the  deficiency  of  oxygen  occasioned  by  it. 
Many  drugs  also  cause  glycosuria,  including  cUrara,  morphine, 
strychnine,  phosphorus,  chloroform,  ether,  and  other  substances, 
some  of  which  may  act  on  the  '  sugar  centre,'  although  others — e.g., 
phosphorus  and  chloroform — are  poisons  which  can  affect  the  liver 
directly.  Injection  of  water  or  physiological  salt  solution  into  the 
bile-ducts,  or  into  the  mesenteric  veins,  or  of  salt  solution  in  consider- 
able amount  into  the  general  circulation,  is  followed  by  glycosuria 
(Fischer,  etc.). 

Diabetes  Mellitus. — In  the  natural  diabetes  of  man,  as  in  all  the 
forms  of  glycosuria  mentioned,  with  the  exception  of  that  produced 
by  phlorhizin,  the  immediate  cause  of  the  glycosuria  is  the  increase 
of  sugar  in  the  blood.  Instead  of  the  i  part  per  1,000,  or  a  little 
more  or  less,  which  constitutes  the  normal  proportion  in  a  healthy 
man,  in  diabetes  3  or  4  parts,  and  in  exceptional  cases  even  7  to 
10  parts  per  1,000  may  be  present.  The  riddle  of  diabetes  is  the 
explanation  of  this  persistent  hyperglycaemia.  Innumerable 
hypotheses  have  been  framed  to  account  for  this,  but  on  the  whole 
three  possibilities  have  been  emphasized:  (i)  That  the  power  ol 
temporarily  storing  carbohydrates  is  deranged;  (2)  that  the  power 
of  the  tissues  to  utilize  carbo-hydrates  {i.e.,  eventually  dextrose) 
is  diminished  or  abolished;  (3)  that  too  much  sugar  is  produced  in 
the  body.  In  addition,  some  writers  have  postulated  a  fourth 
factor  to  explain  certain  cases  (of  so-called  '  renal  diabetes  ') — ^to  wit, 
an  increase  in  the  permeability  of  the  kidneys  for  sugar,  as  in 
phlorhizin  glycosuria.  Lest  the  student  should  be  bewildered 
amongst  all  these  theories,  he  should  take  note  that  there  is  every 


544  METABOLISM,  NUTRITION  AND  DIETETICS 

reason  to  believe  that  diabetes  mellitus  is  not  a  single  pathological 
condition,  but  comprises  a  group  of  such  conditions.  Some  cases 
present  a  picture  conforming  closely  to  one  or  to  another  of  the 
experimental  glycosurias,  but  many  cases  a  picture  compounded  of 
features  characteristic  of  two  or  of  several  of  these  experimental 
conditions. 

It  is  possible  that  in  some  cases  the  sugar  coming  from  the  ali- 
mentary canal  passes  entirely  or  in  too  large  amount  through  the 
liver,  owing  to  a  deficiency  in  its  power  ^  forming  glycogen.  'But 
although  in  certain  cases  of  diabetes  specimens  of  the  hepatic  cells, 
obtained  by  plunging  a  trocar  into  the  liver,  have  been  found  free 
from  glycogen,  in  others  glycogen  has  been  present.  The  muscles 
also  are  usually  stated  to  be  much  poorer  in  glycogen  than  normal 
muscles,  but  this  might  just  as  well  be  the  case  because  glycogen 
was  being  transformed  into  sugar  with  abnormal  ease  as  because 
there  was  interference  with  ghxogen  formation.  Indeed,  it  is  said 
that  in  the  heart  muscle  of  depancreatized  dogs  there  is  more  glyco- 
gen than  in  normal  heart  muscle.  It  must  be  carefully  remembered 
that  the  amount  of  glycogen  present  in  a  tissue  gives  no  information 
as  to  the  rate  at  which  it  is  being  formed  or  decomposed.  And  if 
the  cause  of  the  supposed  defect  in  glycogen-forming  power  be  the 
absence  of  a  glycogen-forming  ferment,  or  its  production  in  too  small 
an  amount,  the  same  circumstance  may  occasion  a  too  tardy  trans- 
formation into  sugar  of  whatever  glycogen  happens  to  be  present. 
In  this  case  the  sugar-regulating  function  of  the  glycogen  store 
would  be  equally  lost,  whether  the  storehouses  were  permanently 
filled  with  long- formed  glycogen  or  only  half-filled  or  empty. 

In  addition  to  an  interference  with  the  due  and  regulated  storage 
of  the  surplus  sugar  as  glycogen,  it  has  usually  been  thought  neces- 
sary for  a  rational  explanation  of  the  facts  of  diabetes,  or  at  least 
of  some  forms  of  it,  to  assume  that  from  some  change  in  the  tissues 
sugar  has  ceased  to  be  a  food  for  them,  or  is  used  up  in  smaller 
amoimt  than  in  the  healthy  body. 

Why  the  tissues  cannot  decompose  and  utilize  dextrose  as  they 
normally  do,  if  it  be  really  the  case  that  they  fail  in  this  regard,  is  a 
question  of  great  interest,  but  as  yet  no  satisfactory  answer  can 
be  given.  It  appears  probable  that  the  failure  occurs  at  one  or  more 
of  the  earliest  stages  in  the  intermediate  metabolism  of  carbo- 
hydrates (p.  534)  or  in  the  preliminary  processes,  whatever  they 
may  be,  which,  ^vithout  profoundly  altering  the  dextrose  molecule, 
prepare  it  for  the  series  of  decompositions,  in  the  course  of  which  it 
eventually  parts  with  all  its  chemical  energy.  For  it  has  been 
shown  that  many  of  the  products  of  the  cleavage  or  oxidation  of 
sugar,  even  those  in  which  the  decomposition  has  proceeded  but  a 
little  way — e.g.,  glyconic  and  glycuronic  acids  (p.  535) — are  com- 
pletely utilized  by  the  tissues  of  diabetics  and  of  depancreatized 


METABOLISM  OF  CARBO-HYDRATES— GLYCOSURIAS       545 

dogs.  And  the  derangement  in  the  normal  sequence  of  events,  of 
whatever  nature  it  may  be,  is  not  so  deep-reaching  as  to  prevent 
the  retracing  of  the  chemical  steps  by  which  sugar  is  synthesized 
from  such  derivatives  of  the  proteins  as  amino-acids  or  tlieir  further 
degradation  products.  As  to  the  actual  cause  of  tlie  alleged  in- 
capacity of  the  tissues  to  consume  dextrose,  the  change  has  by  some 
been  supposed  to  be  the  loss  or  diminution  of  a  glycolytic  ferment 
or  a  substance  necessary  for  the  activation  of  such  a  ferment.  And 
although  the  sugar-destroying  power  of  blood  from  diabetic  patients, 
or  from  animals  in  which  glycosuria  has  been  caused  by  phlorhizin, 
is  not  at  all  inferior  to  that  of  healthy  blood,  it  has  been  maintained 
that  the  intracellular  glycolytic  ferments,  if  such  really  exist,  are 
much  less  active,  especia'ly  in  the  more  severe  forms  of  the  disease, 
which  conform  so  closely  in  their  clinical  manifestations  to  the  pic- 
ture presented  by  the  depancreatized  animal.  Nevertheless,  up  to 
the  present  all  attempts  to  satisfactorily  demonstrate  for  isolated 
tissues  a  loss  or  even  a  diminution  in  the  capacity  to  utilize  dextrose 
have  broken  down.  In  eviscerated  dogs,  for  example— that  is,  in 
preparations  consisting  mainly  of  skeletal  muscle — it  has  been  found 
impossible  to  make  out  an}'  deficiency  as  compared  with  normal 
animals  in  the  amount  of  dextrose  disappearing  in  a  given  time 
from  the  blood,  even  when  the  animals  have  been  deprived  of  the 
pancreas  as  long  as  a  week  before  the  experiment,  and  therefore 
exhibit  the  condition  of  pancreatic  diabetes  in  full  intensity 
(Macleod  and  Pearce).  This  conclusion  has  been  confirmed  for  the 
isolated  heart-lung  preparation. 

As  regards  the  hypothesis  that  an  increased  production  of  sugar 
from  proteins,  or  it  may  be  from  fat,  is  the  essential  proximate  cause 
of  the  hyperglycsemia  and  the  glycosuria,  there  is  no  good  evidence 
that  this  factor,  acting  by  itself  in  the  absence  of  a  derangement  of 
the  regulative  influence  of  the  glycogen  store,  and  in  the  absence  of 
a  derangement  of  the  normal  katabolism  of  dextrose,  is  ever  respon- 
sible for  pathological  diabetes.  But  a  secondary  overproduction 
of  sugar  unquestionably  occurs  in  many  cases.  The  tissues,  bathed 
as  they  are  in  liquids  rich  in  dextrose,  are  nevertheless  starving  for 
sugar,'^if  they  cannot  use  what  is  offered  to  tl.em,  and  the  body 
labours  to  avert  the  famine  by  increasing  its  production  of  sugar, 
the  sugar-forming  tissues  being  stimulated  to  their  task  either 
through  nervous  influences  or  by  chemical  messengers  circulating 
in  the  blood. 

In  depancreatized  dogs,  and  in  dogs  under  the  influence 
of  phlorhizin,  glycerin,  given  by  the  mouth,  causes  an  increase  in 
the  excretion  of  sugar  up  to  two  or  three  times  the  original  amount. 
The  giving  of  fat  d(Jos  not  increase  the  amount  of  sugar  excreted, 
which,  however,  is  increased  by  such  substances  as  egg-yolk,  which 
contain  lecithin.     These  should  accordingly  be  avoided  in  cases  in 

35 


546  METABOLISM,  NUTRITION  AND  DIETETICS 

which  a  strictly  antidiabetic  diet  is  desired.  It  is  much  more  im- 
portant to  exclude  carbo-hydrates  largely  or  entirely  from  the  food, 
although  oatmeal  and  potatoes  are  said  to  occupy  an  exceptional 
position,  and  have  even  been  recommended  as  beneficial.  Calcium 
chloride  has  been  stated  to  diminish  the  sugar  excretion  in  diabetes 
(Boigey),  and  it  has  a  similar  effect  in  certain  of  the  artificial  glyco- 
surias (Brown,  Fischer). 

In  many  cases,  even  when  carbo-hydrates  are  completelj^  or 
almost  completely,  omitted  from  the  food,  sugar,  derived  from  the 
breaking-down  of  proteins,  and  possibly  to  some  extent  from  fats,  still 
continues  to  be  excreted,  although  in  smaller  quantity.  Other  prod- 
ucts formed  or  imperfectly  transformed  in  the  deranged  metabolism, 
especially  of  fats,  such  as  acetone,  aceto-acetic  acid,  and  oxybutyric 
acid  (the  so-called  acetone  bodies) ,  may  also  appear  in  the  urine,  or, 
accumulating  in  the  blood,  may,  by  uniting  with  its  alkalies,  seriously 
diminish  the  quantity  of  carbon  dioxide  which  that  liquid  is  capable 
of  carrying,  and  thus  lead  to  the  condition  known  as  diabetic  coma. 
The  small  amount  of  carbon  dioxide  in  the  venous  blood  may  also  be 
partly  due  to  the  hyperpnoea,  marked  by  increased  depth  of  the 
respiratory  movements  produced  by  stimulation  of  the  respiratory 
centre  by  other  substances  than  carbon  dioxide.  The  increased 
ventilation  causes  a  fall  in  the  carbon  dioxide  pressure  in  the  alveolar 
air,  and  therefore  an  increased  elimination  of  that  gas  from  the  blood. 
This  form  of  coma  appears  to  be  really  in  part  an  acid-poisoning 
comparable  to  the  condition  produced  in  animals  by  doses  of  mineral 
acids  too  large  to  be  neutralized  by  the  ammonia  split  off  from  the 
proteins.  The  administration  of  very  large  doses  of  alkalies  (sodium 
bicarbonate,  for  instance,  to  the  amount  even  of  hundreds  of 
grammes)  has  been  recommended  for  the  treatment  of  this  serious 
complication,  and  in  many  cases  it  is  successful  in  staving  it  off  for 
a  time.  Often,  however,  in  spite  of  a  prolonged  course  of  treatment, 
during  which  the  urine  has  continued  distinctly  alkaline,  fatal  coma 
eventually  occurs.  The  coma  then  is  not  merely  a  symptom  of 
acidosis,  but  is  also  due  to  the  specific  toxic  effects  of  the  acids  even 
when  neutralized.  Other  toxic  products  may  also  be  formed  in  the 
deranged  metabolism.  The  appearance  of  the  acetone  bodies  in 
diabetes  presents  a  problem  which  cannot  be  said  to  have  been  as  yet 
completely  solved.  Oxybutyric  acid,  from  which  aceto-acetic  acid 
and  acetone  are  easily  derived  (p.  558),  seems  to  be  one  of  the  inter- 
mediate steps  in  the  normal  metabolism  of  fats.  But  whereas  under 
ordinary  circumstances  it  is  readily  oxidized  in  the  body,  in  diabetes 
the  power  of  the  tissues  to  burn  oxybutyric  acid  seems  to  suffer  just 
as  does  the  power  to  utihze  dextrose.  The  suggestion  that  in  diabetes 
the  abnormally  great  consumption  of  fat  entailed  by  the  loss  of  avail- 
ability on  the  part  of  the  carbo-hydrates  causes  the  intermediary 
metabolism  of  fats  to  be  scamped,  as  it  were,  is  not  satisfactory. 


THE  METABOLISM  OF  FAT  547 

For  many  animals  and  some  races  of  men  dwelling  in  cold  climates 
consume  with  impunity  much  greater  qui^ntities  of  fat  than  any 
diabetic  organism. 

Section  II. — The  Metabolism  of  Fat. 

Chemistry  of  Fats, — The  fats  are  compounds  (esters)  of  an  alcohol 
with  fatty  acids,  and  can  be  split,  with  assumption  of  water,  ixito  these 
constituents  by  the  action  of  acids  or  alkalies  or  of  enzymes  (lipases). 
In  the  majority  of  the  ordinary  fats,  and  in  all  those  which  are  of 
physiological  importance  (the  triglycerides),  the  alcohol  is  glj^cerin. 
The  fatty  acid  components  which  may  be  united  with  the  glj-cerin  are 
very  numerous,  and  the  physical  properties  of  the  different  fats — e.g., 
their  melting-points  and  solubilities — are  closely  related  to  the  physical 
properties  of  the  corresponding  fatty  acids.  Thus  pahiiitic  and 
stearic  acids  are  solid  at  ordinary  temperatures,  and  so  are  palmitin 
and  stearin,  the  glycerin  esters  or  fats  formed  with  these  acids.  Oleic 
acid,  on  the  contrary,  is  fluid  at  the  ordinary  temperature,  and  the 
corresponding  fat,  olcin,  is  a  liquid  fat  or  oil.  Or;  the  chemical  side 
the  fatty  acids  can  be  distinguished  as  saturated  and  unsaturated. 
The  fatty  acids  of  the  series  CnHgn+i-COOH  are  saturated  acids. 
Where  w  is  o  we  have  formic  acid,  H.COOH;  where  n  is  i,  acetic  acid, 
CH3.COOH;  where  n  is  2,  propionic  acid,  CHg.CHg.COOH;  where 
n  is  3,  butyric  acid,  CH3.CH2.CH2.COOH,  and  so  on,  each  acid  in  the 
series  differing  from  the  one  immediately  preceding  it  in  possessing  an 
additional  CMa  group.  In  the  case  of  the  higher  members  of  the  series 
these  carbon  chains  become  very  long.  In  palmitic  acid,  for  instance, 
CH3.(CH2)i4.COOH,  there  are  fourteen  CHg  groups,  and  in  stearic  acid, 

CH3.(CH2)i6COOH,  sixteen.     Oleic  acid,  ^82"\:  =  c/,^pj  .    COOH 

is  a  representative  of  a  series  of  unsaturated  fatty  acids  whose  general 
formula  is  C,TI2h-i-C00H.  As  the  formula  of  oleic  acid  shows,  the 
unsaturated  fatty  acids  contain  in  their  molecule  two  carbon  atoms 
united  by  a  double  link,  and  one  of  these  valencies  can  be  occupied  by 
halogens  [e.g.,  chlorine)  or  by  oxygen.  Erucic  acid,  a  fatty  acid  occur- 
ring in  certain  vegetable  oils — for  example,  in  rape  oil — also  belongs  to 
this  series,  and  linolic  acid,  found  in  linseed  oil,  to  another  series  of 
unsaturated  fatty  acids.  Then  there  are  the  so-called  oxyfatty  acids, 
which  in  their  turn  comprise  saturated  and  unsaturated  acids.  They 
differ  from  the  ordinary  fatty  acids  in  containing  one  or  more  OH 
groups.  Thus  a  dioxystearic  acid,  €171-133(011)2. COOH,  in  which  two 
of  the  H  atoms  in  stearic  acid  are  replaced  by  OH,  is  found  in  castor-oil. 
It  is  clear,  from  the  great  variety  of  the  fatty  acids,  that  by  their  union 
with  glycerin  (with  loss  of  water)  a  verj^  large  number  of  different  fats 
can  be  formed.  Thus,  when  all  the  OH  groups  in  the  trivalcnt  alcohol  are 
replaced  by  palmitic  acid  we  have  tripalmitin  ;  when  they  are  replaced 
by  stearic  acid,  tristearin  ;  when  they  are  replaced  by  oleic  acid,  triolein ; 
and  so  on.  As  a  group  such  fats  may  be  termed  honio-acid  fats,  since  all 
the  OH  groups  are  replaced  by  the  same  fatty  acid.     Thus — 

CHg.OH         C17H36.COOH         CHa.O.OC.CjvHaB 
CH.OH    -I-  C17H35.COOH   =   CH.O.OC.C17H35-1-3H2O 
CHa-OH         C17H35.COOH         CMa  O.OC.C17H35 

Glycerin.  3  molecules  stearic  acid.  Tristearin.  Water. 


54.8  METABOLISM.  NUTRITION  AND  DIETETICS 

But  it  is  not  necessary  that  each  OH  group  in  the  alcohol  should  be 
replaced  by  the  same  fatty  acid,  and  when  this  does  not  occur  we  have 
hetero-acid  fats.  For  instance,  one  can  be  replaced  by  stearic  acid, 
and  the  remaining  two  by  palmitic  acid,  yielding  a  fat  called  '  stearo- 
dipalmitin.'  Conversely,  one  OH  may  be  replaced  by  palmitic  and  two 
by  stearic  acid,  forming  palmito-distearin.  Similarly,  a  dioleo-stearin 
(glycerin  combined  with  two  molecules  of  oleic  and  one  of  stearic  acid), 
and  an  oleo-distearin  (glycerin  combined  with  two  molecules  of  stearic 
and  one  of  oleic  acid)  are  known.  Such  compounds  have  been  isolated 
from  the  fat  of  animals,  and  also  formed  synthetically.  Again,  each 
of  the  OH  groups  in  the  alcohol  can  be  replaced  by  a  different  fatty  acid. 

It  is  obvious,  then — and  this  is  the  point  to  which  these  chemical 
details  are  intended  to  lead  up — that  the  number  of  different  fats 
which  the  animal  organism  has  at  its  disposal  for  concocting  those 
varied  mixtures  designated  as  body  fat  is  very  great,  and  that  there 
is  room  for  a  considerable  degree  of  specificity  in  the  fat  stores  of 
different  animals,  and  it  may  be  in  the  fat  contained  in  different 
organs  of  the  same  animal,  even  if  this  specificity  is  not  as  marked 
as  in  the  case  of  the  proteins.  It  may  be  added,  in  connection  with 
the  composition  of  the  body  fat,  that  small  quantities  of  free  fatty 
acids  and  of  glycerin  may  be  present ;  but  there  is  reason  to  believe 
that  these  are  simply  the  surplus  of  raw  materials  which  is  about  to 
be  synthetized  to  neutral  fat,  or  the  surplus  of  decomposition 
products  of  the  neutral  fat  which  have  not  yet  left  the  fat  depots 
to  take  their  place  in  the  metabolism  of  the  tissues. 

The  discussion  of  the  metabolism  of  fat  involves  a  study — (i)  of 
the  transformations  and  migrations  of  the  food  fat  before  it  begins 
to  be  utilized ;  (2)  of  the  possible  production  of  fat  from  other  con- 
stituents of  the  food ;  (3)  of  the  processes  and  the  stages  by  which 
fat,  whatever  its  origin,  undergoes  katabolism  to  its  end  products. 
The  fat  of  the  food,  passing  along  the  thoracic  duct  into  the  blood- 
stream, is  soon  removed  from  the  circulation,  for  normal  blood 
contains  only  traces,  except  during  digestion.  Where  does  it  go  ? 
What  is  its  fate  ? 

Transformation  and  Migration  of  the  Food  Fat. — The  presence 
of  adipose  tissue  in  the  body  might  suggest  a  ready  answer 
to  these  questions.  The  fat-cells  of  adipose  tissue  are  ordinary 
fixed  connective-tissue  cells  which  have  become  filled  with  fat, 
the  protoplasm  being  reduced  to  a  narrow  ring,  in  which  the 
nucleus  is  set  like  a  stone.  It  would,  at  first  thought,  seem  natural 
to  suppose  that  the  fat  of  the  food  is  rapidly  separated  by  these 
cells  from  the  blood,  and  slowly  given  up  again  as  the  needs  of  the 
organism  require,  just  as  carbo-hydrate  is  stored  in  the  liver  for 
gradual  use.  And  it  has  been  found  that  a  lean  dog,  fed  with  a 
diet  containing  much  fat  and  little  protein,  puts  on  more  fat,  as 
estimated  by  direct  analysis,  or  keeps  back  more  carbon,  as  esti- 
mated by  measurements  of  the  respiratory  exchange,  than  can  be 
accounted  for  on  the  supposition  that  even  the  whole  of  the  carbon 
of  the  broken-down  protein  corresponding  to  the  excreted  nitrogen 


THE  METABOLISM  OF  FAT  54g 

has  been  laid  up  in  the  form  of  fat.  Even  with  a  diet  of  pure  fat — 
and  with  such  a  diet  digestion  and  absorption  are  carried  on  under 
unfavourable  conditions — more  carbon  is  retained  than  can  have 
come  from  the  metabohsm  of  the  proteins  of  the  body,  as  measured 
by  the  nitrogen  given  off  in  the  urine  and  faeces:  the  fat  passes 
rapidly  from  the  blood  into  the  organs,  and  especially  into  the  liver 
(Hofmann,  Pettenkofcr  and  Voit).  It  is  thus  certain  that  some  of 
the  absorbed  fat  may  be  stored  up  as  fat  in  the  body. 

This  is  borne  out  by  the  careful  experiments  of  Munk  and  Lebe- 
deff,  who  found  that,  when  dogs  are  fed  with  excess  of  foreign  fat 
(linseed  oil,  rape  oil,  mutton  fat),  a  fat  is  laid  down  which  is  quite 
different  from  dog's  fat,  and  has  the  greatest  resemblance  to  the  fat 
of  the  food.  Thus,  when  rape  oil,  which  contains  a  fatty  acid, 
erucic  acid,  not  found  in  animal  fat,  was  given,  erucic  acid  could  be 
detected  in  the  fat  laid  on.  When  the  dogs  were  fed  with  mutton 
fat,  whose  melting-point  is  much  higher  than  that  of  dog's  fat,  the 
fat  laid  on  did  not  melt  till  it  was  heated  to  40°  C.  or  more.  When 
they  were  fed  with  linseed  oil,  the  body-fat  was  found  liquid  even 
at  0°  C.  We  have  already  referred  (p.  438)  to  the  fact  that  neutral 
fat  can  be  built  up  in  the  wall  of  the  intestine  from  fatty  acids  given 
in  the  food.  Munk  has  showm  that  fat  formed  in  this  way  can  also 
be  laid  down  as  body-fat.  But  besides  the  fat  and  fatt}'  acids  of 
the  food,  the  fat  of  the  body  has  other  sources,' and  some  of  it  is 
produced  by  more  complex  processes. 

The  fat  of  a  dog  consists  of  a  mixture  of  palmitin,  olein,  and 
stearin.  When  a  starved  dog  was  fed  on  lean  meat  and  a  fat  con- 
taining palmitin  and  olein,  but  no  stearin,  the  fat  put  on  contained 
all  three,  and  did  not  sensibly  diiler  in  its  composition  from  the 
normal  fat  of  the  dog  (Subbotin).  Stearin  must,  therefore,  have 
been  formed  in  some  way  or  other  in  the  body-  If  it  was  produced 
from  the  olein  and  palmitin  of  the  food,  the  portion  of  these  deposited 
in  the  cells  of  the  adipose  tissue  must  have  undergone  changes  before 
reaching  this  comparatively  fixed  position.  But  there  is  conclusive 
evidence  that  fat  may  be  derived  from  other  sources,  certainly 
from  carbo-hydrates,  and  probably  from  proteins;  and  the  stearin 
may  have  been  formed  from  the  carbo-hydrates  or  proteins  of  the 
food  or  tissues,  and  not  directly  from  fat.  And  if  the  stearin  was 
produced  from  proteins  or  carbo-hydrates,  it  is  evident  that  the 
olein  and  palmitin  might  have  been  formed  in  this  way  too,  the 
portion  of  the  carbo-hydrate  or  protein  devoted  to  this  purpose 
being  sheltered  from  oxidation  by  the  combustion  of  the  fats  of  the 
food.  It  is  well  known  that  not  only  neutral  fats,  but  also  fatty 
acids,  exert  such  a  '  protein-sparing  '  action.  It  is  possible  also  that 
the  fat  which  is  normally  excreted  into  the  intestine  (p.  438),  and 
which  is  perhaps  derived  from  broken-down  proteins,  may  be  re- 
absorbed, and  take  its  place  among  the  fat  '  put  on.' 


550  METABOLISM,  NUTRITION  AND  DIETETICS 

At  this  point  in  the  discussion  it  is  neccss^^.ry  to  remark  that  a 
distinction  ought  to  be  estabhshed  between  that  store  of  surplus  fat 
laid  down  in  the  connective  tissue  which,  in  order  to  avoid  com- 
plicating the  matter  undul}',  has  hitherto  been  referred  to  as  if  it 
constituted  the  whole  of  the  body- fat,  and  the  fat  which  is  contained 
in  greater  or  less  amount  in  all  the  tissue  cells.  The  fat  con- 
tained in  the  tissue  elements — e.g.,  in  the  liver  cells — in  the  visible 
form  of  droplets,  and  which  can  be  easily  extracted  from  them  by 
solvents  such  as  chloroform,  should  also  be  distinguished  from  the 
fat  which  is  so  intimately  incorporated  or  combined  with  the  cell 
substance  that  it  can  only  be  extracted  after  this  has  been  digested 
by  the  aid  of  proteolytic  ferments  or  acids.  The  latter  fraction  of 
the  body-fat  is  probably  an  integral  and  indispensable  constituent 
of  the  protoplasm.  Now,  it  is  in  the  great  fat  depots  of  the  sub- 
cutaneous tissue  and  the  mesenter}-  and  omentum  that  variations 
in  the  proportions  of  the  various  fatty  acids  corresponding  to  varia- 
tions in  the  nature  of  the  food-fat  are  most  easily  produced,  or,  at 
least,  most  easily  observed.  These  depots  are  laid  down,  not  in 
the  interest  of  the  fat  cells  themselves,  but  to  serve  the  purpose  of 
a  reserve  of  fat  which  may  be  drawn  upon  for  the  nutrition  of  the 
body  as  a  whole,  just  as  the  glycogen  store  of  the  liver  forms  a 
general  carbo-h^'drate  reserve.  The  free  fat  in  the  cells  of  the  organs 
is  superficially  analogous  to  the  glycogen  reserves  of  such  tissues 
as  muscles  and  glands,  and  certain  facts  are  known  which  might 
be  interpreted  as  indicating  that  this  fraction  of  the  body-fat,  like 
the  fat  of  the  connective  tissue,  is  not  a  definite  and  specific  mixture 
of  fats  with  an  unvarying  composition  for  each  kind  of  animal,  but 
a  mixture  whose  composition  can  be  made  to  vary  by  altering  the 
nature  of  the  fats  in  the  food.  On  the  other  hand,  the  fat  combined 
in  the  tissues  appears  to  preserve  a  certain  specificity  which  is  inde- 
pendent of  the  fats  supplied  in  the  food.  Thus,  when  dogs  were 
fed  with  rape  oil,  and  had  accumulated  considerable  quantities  of 
this  fat  of  low  melting-point  in  the  subcutaneous  and  other  fat 
depots,  1  he  fat  combined  in  the  organs  remained  in  all  respects  the 
same  as  normal  dog's  fat.  This  was  also  the  case  with  animals 
fed  on  fat  of  high  melting-point,  such  as  sheep's  tallow  (Abderhalden). 
Although  the  liver  appears  to  have  a  special  relation  to  the  metabo- 
lism of  fat,  it  is  not  known  whether  any  particular  organ  is  more 
than  the  rest  responsible  for  the  manufacture  of  this  specific  mix- 
ture of  fats.  It  appears  more  probable  that  each  cell  has  the  power 
of  forming  for  itself  the  characteristic  fats  from  the  crude  materials 
represented  by  the  food-fat  directly  absorbed  from  the  tissue  lymph, 
or  the  fat  of  the  depots  after  it  has  been  mobilized  and  has  found 
its  way  again  into  the  blood,  or,  finally,  from  other  materials  than 
fats,  such  as  dextrose  or  some  of  its  decomposition  products. 

Even  in  the  case  of  the  subcutaneous  and  similar  collections  of 


THE  METABOLISM  OF  FAT  551 

fat,  it  must  be  noted  that  upon  the  whole,  under  normal  conditions, 
it  is  their  specificity  of  composition  rather  than  their  dependence 
upon  the  composition  of  the  fat  mixture  in  the  food  which  is  the 
striking  fact,  and  undue  weight  can  easily  be  given  to  the  results 
of  feeding  experiments  where  great  quantities  of  quite  foreign  fats 
are  administered.  When  small  quantities  of  fats  very  far  removed 
in  their  properties  from  the  normal  fat  of  an  animal  are  given 
in  the  food,  they  are  either  completely  utilized  before  reaching 
the  fat  depots,  or  transformed  into  normal  body- fat,  since  no  change 
whatever  can  be  detected  in  the  latter.  If  they  have  been  utiHzed, 
then  it  may  be  that  a  corresponding  amount  of  fat,  formed,  say, 
from  dextrose,  has  been  laid  down  in  the  fat  stores.  If  this  fat  is 
formed  from  dextrose,  it  will,  of  course,  be  the  kind  of  fat  which 
the  particular  animal  is  accustomed  to  form  from  dextrose — that 
is,  the  fat  characteristic  of  the  animal.  If  the  foreign  fat  is  itself 
transformed  into  body-fat  when  given  in  small  amount,  this  same 
feat  can  without  doubt  be  gradually  accomplished  in  the  case  of 
the  surplus  of  foreign  fat  laid  down  in  the  depots  when  a  large 
quantity  of  it  is  given  in  the  food. 

Formation  of  Fat  from  Other  Sources  than  the  Fat  of  the  Food — 
(i)  From  Carbo- Hydrates. — It  has  been  found  that  the  addition  of 
protein  to  a  diet  of  fat,  and  especially  to  a  diet  of  carbo-hydrate, 
in  larger  amount  than  is  just  necessary  for  nitrogenous  equilibrium 
(p.  594),  leads  to  a  more  rapid  increase  in  the  carbon  deficit — that 
is,  in  the  fat  put  on — than  if  the  minimum  quantity  of  protein 
required  for  nitrogenous  equilibrium  had  been  given.  From  this  it  is 
inferred  that  the  carbonaceous  residue  of  the  broken-down  protein  is 
shielded  from  oxidation  by  the  fat,  and  to  a  still  greater  extent  by 
the  carbo-hydrates,  and  so  retained  in  the  body  as  fat.  And  there 
is  little  doubt  that  the  high  tepute  of  carbo-hydrates  as  fattening 
agents  is  in  part  due  to  their  taking  the  place  of  proteins  and  fats 
in  ordinary  '  current  '  metabolism,  and  so  allowing  body-fat  to  be 
laid  down  from  these.  Voit,  indeed,  has  gone  so  far  as  to  assert 
that  this  is  the  only  sense  in  which  carbo-hydrates  can  be  said  to 
form  fat,  and  that,  in  carnivorous  animals  at  least,  a  direct  con- 
version never  occurs.  But  the  experiments  of  Rubner  have  shown 
that  in  a  dog  fed  with  a  diet  rich  in  carbo-hydrates,  and  containing 
but  little  fat  and  no  proteins  at  all,  the  carbon  deficit  was  greater 
than  could  be  accounted  for  by  the  proteins  being  broken  down  in 
the  body  and  the  fat  of  the  food.  In  the  pig  and  goose,  too,  the 
direct  formation  of  fat  from  carbo-hydrates  has  been  demonstrated. 

For  example,  in  an  experiment  by  Tscherwinsky  two  young  pigs 
of  the  same  litter  were  taken.  They  weighed  respectively  7,300  grammes 
and  7,290  grammes.  One  was  killed,  and  the  amount  of  fat  and  nitrogen 
in  its  body  directly  estimated.  From  the  nitrogen  the  maximum 
quantity  of  protein  which  could  be  present  was  calculated.  The  other 
pig  was  fed  for  four  months  with  barley,  wliich  was  analyzed.  The 
excreta  were  also  analyzed  to  detemune  the  amount  of   unabsorbed 


552  METABOLISM,  NUTRITION  AND  DIETETICS 

fat  and  protein.  At  the  end  of  the  four  months  the  pig  was  killed. 
It  now  weighed  24  kilogrammes,  and  contained  2-52  kilogrammes 
protein  and  9-25  kilogrammes  fat.  Subtracting  the  protein  (0-96  kilo- 
gramme) and  fat  (o-Gg  kilogramme)  originally  present,  i-^d  kilogrammes 
of  protein  and  8-56  kilogrammes  of  fat  must  have  been  put  on.  The 
amount  of  protein  taken  in  the  food  was  7-49  kilogrammes,  and  of  fat 
0'66  kilogramme.  Therefore,  5-93  kilogrammes  of  protein  must  have 
been  used  up,  and  7-90  kilogrammes  of  fat  laid  on.  At  least  5  kilo- 
grammes of  this  fat  must  have  come  from  the  carbo-hydrate  of  the 
food.  Only  a  small  amount  of  the  fat  put  on  could  possibly  have  come 
from  the  protein. 

The  production  of  wax  by  bees,  which  used  to  be  given  as  a  proof 
of  the  formation  of  fat  from  sugar,  is  not  decisive,  for  in  raw  honey 
proteins  are  present ;  and  even  when  bees  fed  on  pure  honey  or  sugar 
manufacture  wax,  it  may  be  derived  from  the  broken-down  proteins 
of  their  own  bodies. 

It  is  probable  that  in  the  formation  of  fats  the  carbo-hydrates 
are  first  split  up  to  some  extent,  and  that  the  fats  are  then  con- 
structed from  their  decomposition  products,  oxygen  being  lost  in 
the  process,  since  fat  is  much  poorer  in  oxygen  than  carbo-hydrate. 
But  the  chemistry  of  the  transformation  as  it  takes  place  in  the  body 
is  still  imperfectly  known,  and  all  that  can  be  done  here  is  to  indicate 
one  or  two  of  the  ways  in  which  chemists  conceive  that  it  may  occur. 

The  formation  of  the  glycerin  component  of  the  neutral  fats  from 
carbo-hydrates  would  appear  to  present  little  difficulty.  In  dis- 
cussing the  formation  of  glycogen  from  glycerin  (p.  528),  it  was  stated 
that  two  molecules  of  glycerose  (glycerin  aldehyde),  a  triose  or  sugar 
with  three  carbon  atoms,  can  be  condensed  to  form  a  hexose  or  sugar 
with  six  carbon  atoms  like  dextrose,  from  the  condensation  or  union 
of  a  number  of  molecules  of  which,  with  abstraction  of  water,  glycogen 
is  built  up.  The  reaction  can  be  worked  equally  well  in  the  reverse 
direction — that  is,  from  the  hexose  dextrose  two  molecules  of  glycerin 
aldehyde  can  be  formed,  and  then  from  each  molecule  of  the  alde- 
hyde, by  reduction,  a  molecule  of  the  alcohol  glycerin.  As  a  matter  of 
fact,  it  has  been  demonstrated  that  glycerin  is  produced  when  the  cor- 
responding aldehyde  is  brought  into  contact  with  minced  liver. 

As  regards  the  fatty  acid  components  of  the  fats,  it  will  be  seen  from 
the  schematic  representation  of  the  katabolism  of  dextrose  on  p.  536 
that  acetic  acid,  a  fatty  acid,  is  represented  at  one  of  the  stages  as  being 
formed  by  the  oxidation  of  a  molecule  of  acetaldehyde.  Lactic  acid 
is  represented  in  the  same  scheme  as  a  previous  stage  in  the  decom- 
position of  dextrose,  and  lactic  acid  can  be  converted  into  acetaldehyde 
and  formic  acid,  the  lowest  of  the  same  series  of  fatty  acids  of  which 
acetic  acid  is  the  next  highest  member.     Thus : 

qJJ^^CH.COOH    =  CHg.C^^  +   H.COOH 

Lactic  acid.  Acetaldehyde.  Formic  acid. 

Aldehydes  (as  well  as  ketones)  have  a  great  capacity  for  entering  into 
reactions  with  other  substances,  and  their  molecules  show  also  a  marked 
tendency  to  combine  with  one  another,  forming  new  compounds  by 
their  condensation.      Thus,  from  two  molecules  of  acetaldehyde  one 


THE  METABOLISM  OF  FAT  553 

molecule  ol  aldol  is  formed,  which  by  transposition  of  certain  groups, 
becomes  butyric  acid,  the  fourth  member  of  the  fatty  acid  series  of 
which  acetic  acid  is  the  second  member,  and  palmitic  and  stearic  acids, 
which  form  such  important  constituents  of  the  ordinary  body -fats, 
the  sixteenth  and  eighteenth  members  respectively.  By  oxidation  aldol 
becomes  /3-oxybutyric  acid,  which  by  further  oxidation  yields  aceto- 
acetic  acid,  compounds  already  referred  to  in  connection  with  diabetes 
(p.  546).     The  following  equations  illustrate  these  reactions: 

CHg.C^^  +  CHg.C^g  =  CH3.CH  (OH)  .CHj.c/^ 

Acetaldehyde.        Acelaldebyde.  Aldol. 

CH3.CH(OH).CH2.CHO=CH3.CH2.CH2.COOH 

Aldol.  Butyric  acid. 

CH3.CH(OH).CH2.CHO-f  O  =CH3.CH(OH).CH2.COOH 

Aldol.  )3-oxybutyric  acid. 

CH3.CH  (OH)  .CH2.COOH  +  O  =  (CH3.CO)  .CH2.COOH  +  HjO 

/S-oxybutyric  acid.  Oxygen.  .\ceto-acetic  acid.  Water. 

By  reduction  aceto-acetic  acid  is  reconverted  into  /3-oxybut^Tic  acid. 
Other  aldehydes  can  react  in  similar  ways,  and  thus  many  of  the  other 
fatty  acids  can  be  formed. 

It  may  be  added  that  acetone  (another  of  the  so-called  acetone 
bodies  which  appear  in  the  urine  in  diabetes  mellitus)  is  easily  obtained 
from  aceto-acetic  acid  by  the  splitting  off  of  carbon  dioxide.     Thus : 

(CH3.CO).CH,.COOH  =CH3.CO.CH3-|- CO2 

Aceto-acetic  acid.  Acetone.  Carbon  dioxide. 

Formation  of  Fat — (2)  From  Protein. — Dry  protein  contains  on 
the  average  16  per  cent,  of  nitrogen  and  50  per  cent,  of  carbon,  and 
urea  contains  46  per  cent,  of  nitrogen  and  20  per  cent,  of  carbon. 
Urea  is  therefore  three  times  as  rich  in  nitrogen  as  the  protein  from 
which  it  is  derived,  but  two  and  a  half  times  poorer  in  carbon;  and 
less  than  one-seventh  of  the  carbon  of  protein  will  be  eliminated 
in  a  quantity  of  urea  sufficient  to  carry  off  all  the  nitrogen.  It 
is  probable  that  a  portion  of  the  remaining  carbon  may,  aiter  passing 
through  various  stages,  take  its  place  as  the  carbon  of  fat.  We 
have  seen  that  certain  amino-acids  derived  from  proteins  can  be 
converted  into  dextrose,  and  that  dextrose  can  be  converted  into 
fat.  So  that  the  mere  question  whether  carbon  atoms  or  carbon 
chains  originally  present  in  protein  molecules  are  ever  capable  of 
appearing  in  fat  molecules  can  be  straightway  answered  in  the 
afi&rmative.  But  it  is  still  in  doubt  whether  amino-acids  can  be 
transformed  into  glycerin  or  into  fatty  acids,  or  into  both,  by 
processes  which  do  not  involve  the  production  of  dextrose  from 
them.  And  in  any  case  proof  is  required  that  the  extent  of  the 
transformation,  let  the  steps  be  what  they  may,  is  great  enough 
to  be  satisfactorily  demonstrated.  In  regard  to  this  point  it  must 
be  said  that  absolutely  flawless  experiments  to  prove  the  direct 
production  of  fat  from  protein  seem  still  to  be  wanting. 


554  METABOLISM.  NUTRITION  AND  DIETETICS 

Phosphorus  Poisoning  and  Migration  of  Fat. — In  the  experiments 
of  Bauer,  the  amount  of  oxygen  consumed  and  of  carbon  dioxide 
and  nitrogen  excreted  was  determined  in  starving  dogs.  Phosphorus, 
which,  as  is  well  known,  causes  extensive  fatty  changes  in  the 
organs,  was  then  administered  in  small  doses  for  several  days. 
The  excretion  of  nitrogen  was  doubled,  the  excretion  of  carbon 
dioxide  and  the  consumption  of  oxygen  diminished  to  one-half.  When 
the  animals  died,  in  a  few  days,  the  organs  were  all  found  loaded  with 
fat.  In  one  case  42-4  per  cent,  of  the  solids  of  the  muscles  and  30  per 
cent,  of  the  solids  of  the  liver  consisted  of  fat.  This  is  much  more  than 
the  normal  amount.  It  was  assumed  that  the  fat  could  not  have  been 
simply  transferred  from  the  adipose  tissue,  since  the  dog  had  been 
starved  for  twelve  days  before  the  phosphorus  was  given,  and  died  on 
the  twentieth  day  of  starvation.  Now,  after  such  a  period  of  hunger 
the  amount  of  fat  in  the  adipose  tissue  is  greatly  reduced.  It  was  there- 
fore concluded  that  the  source  of  the  fat  could  only  have  been  the 
broken-down  protein.  Since  the  nitrogen  excretion  was  increased,  while 
the  carbon  excretion  was  diminished,  it  was  supposed  that  a  residue 
rich  in  carbon  must  have  been  split  off  from  the  proteins,  and,  remaining 
unbumt  in  the  body,  must  have  been  converted  into  fat.  Experiments 
of  this  kind  are  open  to  criticism  on  several  grounds,  but  especially  on 
this :  that  unless  the  fat-content  of  the  whole  body  before  the  adminis- 
tration of  the  poison  is  known,  it  is  impossible  to  be  sure  that  the  fat 
in  a  particular  tissue  has  not  been  increased  simply  by  the  transportation 
of  fat  from  some  other  tissue.  It  has  been  conclusively  shown  that 
migration  of  preformed  fat  docs  occur,  and  on  an  extensive  scale,  in 
phosphorus  poisoning.  For  example,  a  dog  was  fed  for  a  time  with 
sheep's  tallow,  and  fat  was  laid  down  in  its  adipose  tissue  with  the 
physical  and  chemical  characters,  not  of  dog's,  but  of  sheep's  fat.  The 
animal  was  then  poisoned  with  phosphorus,  and  the  fat  which  accumu- 
lated in  the  liver  examined.  It  also  resembled  sheep's  fat,  as  it  should 
have  done  had  it  migrated  from  the  adipose  tissue,  and  not  dog's  fat, 
as  it  might  have  been  expected  to  do  had  it  been  formed  in  the  hepatic 
cells  from  protein .  The  ease  with  which  connective-tissue  fat — i.e.,  food 
fat — migrates  to  the  liver  suggests,  with  other  facts,  that  the  liver  has  a 
special  relation  to  the  transformation  of  this  fat  into  the  fat  of  the  organs. 
This  '  organized  '  intracellular  fat  differs  in  various  ways  from  the  fats 
of  adipose  tissue.  Its  '  iodine  value  '  (p.  4)  is  higher  (Leathes),  and  a 
large  proportion  of  it  consists  of  phosphatide  lipoids  (p.  562). 

The  most  convincing  evidence  that  fat  is  not  produced  in  increased 
amount  under  the  influence  of  phosphorus  has  been  obtained  by  deter- 
mining by  actual  analysis  the  total  fat  in  animals,  then  poisoning 
similar  animals  with  phosphorus  and  again  estimating  the  total  fat. 
Far  from  being  increased,  the  fat  may  even  be  decreased  in  the  poisoned 
animals  (Taylor,  etc.).  There  is  no  ground,  then,  for  the  assumption 
that  phosphorus  and  other  substances,  like  arsenic,  antimony,  etc.,  which 
bring  about  so-called  '  fatty  degeneration  '  of  the  organs,  act  by  causing 
or  accelerating  the  transformation  of  protein  into  fat.  Yet  there  is  good 
evidence  that  they  do  accelerate  the  decomposition  of  protein,  or  at 
least  interfere  with  its  normal  metabolism,  for  after  phosphorus  poison- 
ing amino-acids  (Icucin,  tyrosin,  glycin)  appear  in  the  urine.  The 
observations  of  Lusk  and  his  pupils  indicate  that  phosphorus  does  not 
directly  increase  the  amount  of  protein  broken  down,  but  does  so 
indirectly,  by  favouring  the  conversion  of  the  carbohydrate -like  radicle 
of  the  protein  molecule  into  leucin,  tyrosin,  and  perhaps  fat,  and 
thereby  necessitating  an  increased  consumption  of  protein. 

A  celebrated  experiment,  performed  nearly  forty  years  ago,  was  long 


THE  METABOLISM  OF  FAT  555 

supposed  to  furnish  an  absolute  proof  of  the  formation  of  fat  from 
protein,  under  strictly  physiological  conditions,  although  in  a  humble 
form  of  animal  life.  Maggots  were  allowed  to  develop  from  the  egg  on 
blood  containing  a  known  amount  of  fat.  The  quantity  of  fat  in  the 
eggs  was  also  known.  After  the  maggots  had  grown,  ten  times  as 
much  fat  was  found  in  them  as  had  been  contained  in  the  blood  and 
eggs  together.  The  trifling  quantity  of  sugar  in  the  blood  was  utterly 
inadequate  to  account  for  the  fat,  which,  it  was  concluded,  must  there- 
fore have  come  from  the  proteins  of  the  blood  (Hofmann).  It  can  be 
objected  to  this  experiment  that  no  precautions  were  taken  to  prevent 
the  growth  of  micro-organisms  on  the  blood,  and  fat  might  have  been 
formed  by  them  from  the  proteins.  Further,  the  fat  estimations  would 
scarcely  pass  muster  according  to  the  present  standards. 

The  experiments  of  Pettcnkofer  and  Voit,  which  were  supposed  to 
have  demonstrated  that  in  the  higher  animals  also  fat  is  formed  from 
proteins  under  normal  conditions,  are  in  the  same  position.  According 
to  them,  a  dog  fed  for  a  time  on  a  liberal  diet  of  lean  meat  may  go  on 
excreting  a  quantity  of  nitrogen  equal  to  that  in  the  food,  while  there 
is  a  dcficienc}'  in  the  carbon  given  off.  Or  if  the  dog  is  not  in  nitrog- 
enous equilibrium  (p.  591),  but  putting  on  nitrogen  in  the  form  of 
'  flesh,'  the  deficiency  in  the  carbon  given  off  may  be  too  great  in  pro- 
portion to  the  nitrogen  deficit  to  warrant  the  assumption  that  all  the 
retained  carbon  has  been  put  on  in  the  form  of  protein.  In  either  case, 
carbon  in  large  amount  can  only  come  from  the  proteins  of  the  food, 
and  can  only  be  stored  up  in  the  body  in  the  form,  of  fat.  For  lean  meat 
contains  but  a  trifling  quantity  of  carbon  in  any  other  proximate 
principle  than  protein,  and  the  non-protein  carbon  of  the  animal  body 
is  only  to  a  ven>^  small  extent  contained  in  carbo-hydrates  or  other 
substances  than  fat. 

Pfliiger  has  criticized  these  experiments,  and  has  shown  that  lean 
meat  contains  more  fat  than  was  supposed,  and  this  is  now  generally 
admitted.  He  has  endeavoured  to  show  that  the  fat  and  glycogen  in 
the  meat  given  to  the  animals  fully  accounts  for  the  carbon  retained. 
Pfliiger,  indeed,  takes  up  the  position  that  the  fat  of  the  body  comes 
exclusively  from  the  carbo-hydrates  and  fats  of  the  food,  and  not  at  all 
from  the  proteins.  But  there  is  little  doubt  that  in  this  he  has  gone  too 
far,  although  his  criticism  has  rendered  it  impossible  any  longer  to  appeal 
to  Pettenkofer  and  Voit's  results  as  good  evidence  on  the  other  side. 

If  none  of  the  supposed  quantitative  proofs  of  the  conversion  of 
proteins  into  fat  which  have  hitherto  been  brought  forward  are 
free  from  flaw,  the  same  is  true  of  the  alleged  qualitative  indications 
of  its  possibiHty  and  of  its  actual  occurrence.  The  accumulation 
of  fat  between  the  hepatic  cells  caused  by  phlorhizin  is,  at  the  best, 
no  better  evidence  than  the  accumulation  within  the  cells  in  phos- 
phorus poisoning.  The  formation  of  adipocere  (a  cheesy  substance, 
rich  in  fatty  acids  united  with  calcium  or  ammonium),  sometimes 
seen  in  dead  bodies  which  have  remained  a  long  time  under  water 
or  in  moist  graveyards,  is  largely,  if  not  entirely,  due  to  the  fat 
already  present  in  the  parts  which  have  undergone  the  change, 
or  to  fat  removed  by  the  water  from  other  parts  of  the  body. 
If  any  portion  of  the  adipocere  represents  fat  formed  from  protein, 
this  transformation  may  well  be  credited  to  the  numerous  micro- 
organisms present,  and  throws  no  light  upon  the  question  of  fat 
formation  in  the  normal  organism.     The  fat  in  the  cells  of  the 


556  METABOLISM.  NUTRITION  AND  DIETETICS 

sebaceous  glands,  and  of  the  mammary  glands,  may  be  produced 
from  protein  by  a  transformation  of  the  cell-substance.  But  abso- 
lutely convincing  proof  is  wanting.  The  old  idea  that  the  cells  of 
these  glands  underwent  a  physiological  process  of  transformation 
into  fat  analogous  to  the  fatty  degeneration  of  pathology,  and  then 
broke  down  bodily  into  the  secretion,  has  been  long  since  disproved 
for  milk  formation,  and  is  probably  erroneous  also  as  regards  the 
secretion  of  sebum.  The  rule  which  experience  has  taught,  that 
a  woman  during  lactation  requires  an  excess  of  proteins  in  her  food 
corresponding  not  only  to  the  proteins,  but  also  to  the  fat  given  off 
in  the  milk,  suggests  such  an  origin  for  the  milk-fat,  but  does  not 
prove  it.  Other  fat-containing  secretions  are  the  ear-wax  formed 
by  glands  in  the  wall  of  the  external  auditory  meatus,  and  the 
smegma  formed  by  the  glands  of  the  prepuce,  but  nothing  is  known 
of  the  sources  from  which  the  fatty  substances  are  derived. 

The  Intermediary  Metabolism  of  Fat. — The  mechanism  and  the 
stages  of  the  transformation,  including  the  migration,  of  fats  is 
not  well  understood — indeed,  not  as  well  as  that  of  the  carbo- 
hydrates. Many  of  the  tissues  contain  intracellular,  soluble, 
fat-splitting  ferments  called  lipases,  especially  the  liver,  the 
active  mammary  gland,  and  the  intestinal  mucosa.  We  have 
already  seen  that  there  is  evidence  that  these  lipases,  like  some 
other  enzymes,  have  a  reversible  action.  They  are  either  fat- 
splitting  or  fat-forming  ferments,  according  to  the  conditions 
(Kastle  and  Loevenhart).  It  is  stated  that  the  perfectly  aseptic 
blood  does  not  split  ordinary  neutral  fats,  although  it  contains  a 
ferment  which  splits  up  monobutyrin  (glycerin  butyrate)  into 
glycerin  and  butyric  acid. 

The  question  how  the  fat,  after  absorption  from  the  intestine, 
passes  from  the  blood  into  the  cells,  and  how  it  is  enabled  again  to 
pass  out  of  the  fat-cells  when  the  needs  of  the  tissues  call  for  its 
mobilization,  cannot  at  present  be  definitely  answered.  It  is 
possible  that  just  as  fat  is  split  in  the  lumen  of  the  intestine  before 
being  absorbed,  and  then  rebuilt  in  the  epithelium,  so  it  is  split  in 
the  blood  or  in  the  lymph  before  being  taken  up  by  the  fat-cells. 
The  lipase  in  these  cells  would  then  be  capable  of  synthetizing  the 
glycerin  and  fatty  acids  to  fat  in  their  interior.  When  the  fat  is 
about  to  pass  out  of  the  cells  in  response  to  the  call,  of  whatever 
nature  it  is,  of  the  tissues  for  fat,  it  may  again  be  split,  resynthetized 
in  the  blood,  and  again  hydrolysed  for  entrance  into  the  tissue 
cells.  Or  it  may  be  carried  to  the  cells  in  the  form  of  glycerin  and 
fatty  acids,  or  soaps,  in  such  small  concentration  as  to  be  harmless, 
and  there  built  up  again  into  the  original  fat,  or  transformed  into 
other  fats  characteristic  of  the  particular  tissues,  including  the  fatty 
acid  components  of  the  phosphatides,  or  utilized  without  synthesis 
into  fat.    An  alternative  hypothesis  avoids  this  series  of  decomposi- 


THE  METABOLISM  OF  FAT  557 

tions  and  syntheses  by  assuming  that  the  fat  passes  in  the  lorm  of 
very  fine  droplets  through  the  walls  of  the  cells  and  of  the  capil- 
laries. The  reader  will  observe  that  we  seem  to  be  discussing  again, 
and  almost  in  the  same  terms,  the  question  of  the  absorption  of  fat 
from  the  intestine.  It  is  indeed  at  bottom  the  same  question,  and 
it  might  be  argued  that  by  analogy  it  should  receive  the  same  solu- 
tion. Analogy,  however,  is  a  dangerous  guide  in  such  matters,  and 
it  is  even  more  difficult  to  secure  an  unambiguous  experimental  test 
of  the  manner  in  which  the  internal  migration  of  fat  is  accomplished 
than  to  secure  the  like  for  its  absorption  from  the  digestive  tube. 

As  to  the  ultimate  fate  of  the  fat,  from  whatever  source  it  may 
be  derived,  our  knowledge  may  be  compressed  into  very  few  sen- 
tences: Sooner  or  later  it  is  split  and  oxidized  to  carbon  dioxide  and 
water,  its  energy  being  converted  into  heat  or,  directly  or  indirectly,  into 
mechanical  or  other  functional  work ;  some  of  the  fat  absorbed  from  the 
intestine  rapidly  undergoes  this  change  without  entering  the  fat-cells  of 
the  adipose  tissue.  A  portion  of  the  fat  may  be  changed  into  carbo- 
hydrates. This  has  been  proved  for  the  glycerin  component  ;  its  possi- 
bility must  be  admitted  for  the  fatty  acids,  but  proof  has  not  yet  been  given. 

Of  the  intermediate  stages  by  which  the  fatty  acids  are  degraded 
into  the  simple  end  products  but  little  is  surely  known.  Included 
among  these  stages  must  be  the  compounds  with  which  the  forma- 
tion of  the  acetone  bodies  (p.  553)  starts,  if  and  in  so  far  as  their 
formation  is  a  normal  event  which  is  merely  unveiled  by  the  dis- 
turbance of  the  ordinary  course  of  the  metabolism  in  diabetes. 
Among  these  intermediate  stages  must  also  be  included,  it  is  to  be 
supposed,  the  compounds,  whatever  they  may  be,  which  act  as 
connecting  links  between  the  currents  of  fatty  acid  and  of  carbo- 
hydrate metabolism,  and  with  which  the  transformation  of  fatty 
acids  into  carbo-hydrates  commences,  if  this  occurs  at  all. 

According  to  the  observations  of  Knoop,  the  saturated  as  well  as 
some  of  the  other  series  of  fatty  acids  when  oxidized  decompose  in  a  very 
characteristic  way.  As  already  remarked,  these  acids  are  made  up  of  a 
larger  or  smaller  number  of  CHj  groups  forming  a  chain  which  at  one 
end  terminates  with  a  carboxyl  (COOH)  group,  and  at  the  other  with  a 
CH3  group.  The  carbon  atoms  in  the  chain  are  designated  by  Greek 
letters,  a,  /3,  etc.,  the  a  position  being  that  next  the  carboxyl  group, 
the  /3  position  one  remove  from  the  carboxyl  group,  and  so  on.  Accord- 
ing to  Knoop,  the  oxidation  of  the  fatty  acid  chain  takes  place  in  such 
a  way  that  the  chain  is  shortened  by  the  cutting  off  from  the  carboxyl 
end  the  a  CH2  group  along  with  the  carboxyl  group,  while  in  place  of  the 
^CH2  group  there  is  left  a  carboxyl  group,  an  operation  which  might 
be  fancifully  compared  to  the  naval  manoeuvre  of  breaking  the  enemy's 

„,         ,  .  .,    CHo.CHo.CHa.CHo.  I  CH,.COOH, 

line.      Thus   from   caproic   acid    e^yn\a  we 

get  by  oxidation   butyric  acid,  CHg.CHa.CHj.COOH,  ^^^^^  dioxide 

and  water.     It  appears  that  the  oxidation  proceeds  in  two  stages,  the 
hydrogen  of  the  /3  group   being   first  oxidized  with  formation  of  an 


558  METABOLISM.  NUTRITION  AND  DIETETICS 

oxyacid  oxycaproic  acid,   CH3.CH2.CH2.CHOH.CHa.COOH,    which  is 

then  by  further  oxidation  converted,  with  loss  of  two  carbon  atoms, 

into  butyric  acid.     The  oxidation  process  may  then  start  afresh  on 

the  /3  group  of  butyric  acid.     On  the  long  carbon  chains  of  the  higher 

fatty  acids  this  operation  may  be  repeated  again  and  again,  the  chain 

losing  two  atoms  of  carbon  at  each  attack.     If  this  represents  what 

occurs  in  the  normal  metabolism,  the  groups  cut  off  may  then  and  there 

undergo  the  fate  of  the  ships  isolated  by  a  successful  application  of^the 

manoeuvre  alluded  to,  complete  destruction — that  is  to  say,  oxidation 

to  the  end  products  carbon  dioxide  and  water,  a  portion  of  the  energy 

of  the  fatty  acid  being  thus  liberated  at  each  oxidation  of  the  /3  group. 

Eventually  a  fatty  acid  or  acids  with  very  few  carbon  atoms  will  be 

left.     There  is  some  reason  to  think  that  acetic  acid    (and   perhaps 

similar  simple  acids)  may  be  one  of  the  normal  stages  in  the  deconir 

position.     Thus,    butyric   acid   may   first  yield    by   oxidation   of   the 

^,  . ,     ^         ,     ,      .  . ,      CHo.CHOH.CHo.COOH, 

/3    group    the     oxyacid    p-oxybutyric     acid,  ^^  ^     * 

which  by  further  oxidation  of  the  j8  group  and  the  cutting  off  of  the  a 
and  carboxyl  groups  would  give  CH3.COOH,  or  acetic  acid. 

If  this  is  the  general  course  of  the  oxidation  of  the  fatty  acids  in 
the  body,  it  is  to  be  assumed  that  numerous  intermediate  stages 
unrepresented  in  such  a  simple  scheme  may  exist.  Thus  it  is  known, 
as  has  been  mentioned  more  than  once  in  other  connections  (p.  553), 
that  ^-oxybutyric  acid  by  oxidation  yields  aceto-acetic  acid,  by 
losing  from  the  /3  group  two  atoms  of  hydrogen  which  unite  with 
oxygen  to  form  water.  A  molecule  of  aceto-acetic  acid  contains 
the  elements  of  two  molecules  of  acetic  acid  minus  the  elements  of 
one  molecule  of  water.  It  is  therefore  possible  that  aceto-acetic 
acid,  if  it  is  a  normal  stage  in  the  katabolism  of  fatty  acids,  yields 
by  its  hydrolysis  as  a  further  step  acetic  acid,  according  to  the 
equation 

CH3.CO.CH2.COOH-|-HaO=2(CH3.COOH). 

Aceto-acetic  acid.  Acetic  acid. 

It  is  worth  while,  perhaps,  to  point  out  once  more  that  even  the 
relatively  simple  products  now  arrived  at  are  not  necessarily  at 
once  completely  oxidized  to  their  end  products.  That,  it  is  to  be 
assumed,  will  depend  upon  the  needs  of  the  organism.  Acetic  acid, 
for  example,  when  added  to  blood  and  perfused  through  the  sur- 
viving liver,  can  be  transformed  into  aceto-acetic  acid,  and  may 
thus  become  the  starting-point  of  new  syntheses. 

The  Liver  and  Fats. — The  liver  seems  to  play  an  important  part  in 
the  metabolism  of  fat,  as  it  does  in  the  metabolism  of  carbo-hydrates 
and  of  proteins.  It  contains  an  oxidizing  ferment,  ^-oxybutyrase 
(or  /3-hydroxybutyrase),  which  transforms  /S-oxybutyric  acid  into 
aceto-acetic  acid  (Dakin).  This  oxidation  appears  to  occur  in  the 
normal  as  well  as  in  the  diabetic  organism.  The  liver  seems  also  to 
possess  the  power  of  transforming  aceto-acetic  acid  into  acetone,  a 
reaction  which  does  not  involve  an  oxidation,  and  this  may  also  be 
accomplished  by  means  of  an  enzyme.     But  it  is  not  at  all  likely 


THE  METABOLISM  OF  FAT  559 

that  acetone  forms  a  stage  in  the  normal  katabohsm  of  the  fatty 
acids  or  of  the  /3-oxyacids  derived  from  them.  The  importance  of 
the  liver  in  the  metabolism  of  fats  is  further  indicated  by  the  extent 
of  the  migration  of  fat  to  that  organ  when  the  fat  stores  are  mobilized 
in  unusual  amount  (p.  554).  The  reason  for  this  migration  seems 
to  be  that  the  fats  undergo  preparatory  changes  which  facilitate 
their  utilization  by  the  tissues.  For  example,  there  is  evidence 
that  saturated  fatty  acids  are  changed  in  the  liver  into  unsaturated 
acids,  which  are  then  carried  to  the  organs  to  be  metabolized. 
The  desaturation  may  serve  the  purpose  of  facilitating  the  rupture 
of  the  long  carbon  chains,  or  their  capacity  for  entering  into  reac- 
tions with  other  substances,  at  the  points  where  double  links  exist 
between  carbon  atoms  (p.  547). 

Non-Nutritive  Functions  of  Fat. — In  connection  with  the  metabo- 
lism of  fat,  it  ought  to  be  noted  that,  in  addition  to  their  value  as 
reserve  material  for  the  nutrition  of  the  body,  the  deposits  of  fat 
under  the  skin  and  in  other  situations  perform  important  functions 
in  protecting  delicate  structures  from  mechanical  injury,  in  facili- 
tating their  movements  upon  each  other,  and  in  hindering  the  loss 
of  heat.  It  would  doubtless  be  a  gross  exaggeration  to  say  that  the 
mechanical  and  physical  properties  of  the  fat  depots  are  as  im- 
portant in  comparison  to  their  chemical  relations  as  is  the  case  for 
the  bones  and  ligaments,  but  it  would  be  an  error  not  less  gross  to 
consider  them  as  of  little  account.  It  will  even,  perhaps,  be 
thought  not  unworthy  of  mention,  from  the  point  of  view  of  the 
propagation  of  the  race,  that  in  the  human  species,  at  least,  the 
amount  and  distribution  of  the  cutaneous  fat  plays  a  part  of  some 
consequence  in  the  aggregate  of  qualities  which  determine  the 
physical  attractiveness  of  the  individual,  especially  of  the  female, 
although  the  standard  in  this  regard  varies  widely  in  different 
communities. 

It  is  perhaps  partly  because  the  fat  depots  have  important 
mechanical  functions  that  the  fat  reserve  is  far  less  mobile  than  the 
glycogen  reserve.  The  semi-solid  panniculus  adiposus,  the  fatty 
tissue  around  the  great  nerve  trunks,  between  the  muscles,  around 
the  eyeball,  on  the  soles  of  the  feet,  etc.,  possesses  as  a  protective 
packing  the  good  qualities  of  a  water  cushion  with  none  of  its  dis- 
advantages. But  if  the  fat-cells  were  subject  to  sudden  depletion,  as 
the  hepatic  cells  are — nay,  in  still  greater  degree,  since  they  contain 
hardly  any  protoplasm — ^they  would  never  serve  for  such  a  function. 
Of  course,  in  the  emergency  of  starvation,  when  even  the  glands 
and  the  muscles  themselves  are  wasting,  the  fat  reserves  are  neces- 
sarily mobilized,  let  their  mechanical  functions  suffer  as  they  may. 

Obesity. — The  proportion  oi  the  total  mass  of  the  body  which  is  made 
up  of  fat  varies  greatly  in  different  individuals,  and  often  in  the  same 
individual  at  ditlcrcnt  stages  in  life.     When  the  accumulation  of  fat 


56o  METABOLISM.  NUTRITION  AND  DIETETICS 

t 

passes  beyond  a  certain  point  it  causes  obvious  changes  in  the  contours 
of  the  body,  and  often  some  embarrassment  in  its  movements.     This 
condition  is  termed  obesity.     It  is  extremely  difficult  to  say  when  the 
condition  oversteps  the  physiological  boundary  and  becomes  actually 
pathological.     Some  individuals  who  are  notoriously  stout  are  noted 
also  for  their  intellectual  activity,  and  may  not  fall  below  the  average 
even  in  the  ordinary  kinds  of  physical  effort.     It  would  be  an  exaggera- 
tion to  speak  of  such  persons  as  suffering  from  a  disease .     In  other  cases 
the  pathological  stamp  is  clearly  imprinted  upon  the  metabolic  anomaly 
which  leads  to  the  overfilling  of  the  fat  depots.     This  is  perhaps  best 
illustrated  in  those  cases  of  extreme  obesity  in  children  where,  in  spite 
of  the  intense  metabolism  associated  with  growth,  with  the  restless 
muscular  activity  characteristic  of  that  age,  and  with  the  relatively 
great  surface  through  which  heat  is  lost,  great  quantities  of  fat  continue 
to  be  put  on.     Muscular  activity  by  itself  is  no  certain  antidote  to  or 
prophylactic  against  obesity,  and  it  is  a  mistake  to  suppose  that  the 
condition  is  exceedingly  rare  among  manual  workers  sufficiently  well 
paid  to  be  able  to  gratify  their  tastes  in  the  quality  and  quantity  of 
their  food.     Statistics  or  rough  estimates  covering  the  whole  of  the 
hand-workers  of  a  country  throw  no  light  on  such  a  question,  for  few 
indeed  are  the  lands  where  the  masses  of  the  people  have  such  well-filled 
purses  that  they  are  able  to  nourish  themselves  according  to  their  wishes. 
While  it  is  true  that  the  great  majority  of  normal  individuals  (although 
not  all,  since  even  in  the  fattening  of  stock  for  market  some  animals  are 
rejected  as  bad  feeders)  can  be  compelled  to  lay  on  fat  when  overfed 
with  fat  and  especially  with  carbo-hydrates,  and  prevented  from  taking 
much  exercise  or  from  losing  heat  freely,  the  most  important  factor  in 
the  excessive  storing  of  fat  by  human  beings  leading  a  free  life  seems  to 
be  an  anomaly  in  the  metabolism  which  permits  the  machine  to  be  run  on 
less  than  the  usual  amount  of  fuel.     From  the  point  of  view  of  thermo- 
dynamics the  fat  man,  in  very  many  instances  at  least,  grows  fat  and 
fatter  because  his  body  is  a  machine  whose  '  efficiency  '  is  greater  than 
the  normal — that  is  to  say,  a  machine  which  is  capable  of  doing  a  given 
amount  of  work  and  of  keeping  itself  in  repair  with  a  food  intake  of 
smaller  heat  value  than  is  usually  needed.     Whether  this  anomaly  is  to 
be  considered  a  metabolic  fault  or  a  metabolic  virtue  depends  largely 
upon  the  ease  with  which  the  intake  is  adjusted  to  the  actual  require- 
ment of  the  body.     If  the  adjustment  is  rendered  accurate,  the  man 
with  the  anomalous  tendency  to  put  on  fat,  the  adiposophil,  ashe  might 
be  called,  is  in  all  probability  j  ust  as  weU  off  in  every  physiolog  icalsentii 
on  a  smaller  diet  than  a  so-called  normal  individual  of  the  same  age, 
weight,  and  daily  routine,  on  a  larger  quantity  of  food,  and   on  this 
smaller  diet  he  does  not  become  fat.     In  this  connection  it  may  be 
recalled  that,  in  speaking  of  the  blood-flow  in  the  hands  and  feet  (p.  127), 
which  are  in  this  relation  to  be  regarded  as  essentially  an  '  outcrop  ' 
of  the  cutaneous  circulation,  it  was  pointed  out  that  some  healthy 
persons  have  habitually  small  flows  and  a  habitually  cool  skin  which 
perspires  little,  in  comparison  with  others  living  practically  the  sam  e  life. 
It  was  suggested  that  this  difference  in  the  blood-flow  through  the  skin, 
w^hich  of  course  would  correspond  with  a  difference  in  the  rate  of  heat 
loss,  and  therefore  in  the  rate  of  heat  production,  may  be  correlated  with 
a  difference  in  the  intensity  of  the  metabolism  and  the  intake  of  food. 

The  difficulty  of  adjusting  the  appetite  to  the  actual  physiological 
requirement  is  perhaps  the  real  anomaly  in  adiposophilia.  Several 
factors  seem  to  be  involved  in  the  group  of  sensations  comprised  under 
appetite  and  hunger  (Chapter  XVIII),  and  the  onset  and  intensity  of 
these  sensations  are   unquestionably  influenced   by   habit.     The  real 


THE  METABOLISM  OF  FAT  56t 

question  in  many  cases  of  obesity  may  be  not  why  the  metabolism  is 
managed  so  parsimoniously — that  is,  in  the  pliysiological  sense,  so 
thriftily — but  why  the  fat  man  or  the  man  tending  to  become  fat  still 
experiences  so  strong  a  desire  for  food  after  he  has  eaten  what  in  pro- 
portion to  his  metabolic  wants  is  enough,  whereas  the  man  with  no 
tendency  to  obesity  is  no  longer  hungry  after  he  has  eaten  an  amount 
of  food  sufficient  for  the  requirements  of  his  tissues.  Is  there  here 
perhaps  an  anomaly  in  the  nervous  mechanism  in  virtue  of  which,  for 
instance,  the  gastric  hunger  contractions  are  more  readily  initiated 
and  less  easily  stilled  than  in  the  normal  person  ?  It  is  recognized 
that  in  the  usually  much  more  serious  anomaly  of  the  carbo-hydrate 
metabolism,  diabetes  mcllitus,  the  nervous  element  may  be  important. 
The  influence  of  the  loss  of  certain  of  the  internal  secretions  on  the 
deposit  of  fat  will  be  alluded  to  in  the  next  chapter. 

In  the  treatment  of  obesity  the  factor  of  appetite  and  hunger  control 
has  to  be  specially  kept  in  mind.  Bulky  but  comparatively  innu- 
tritions food,  such  as  green  vegetables,  e.g.,  in  the  form  of  salads,  should 
form  an  important  constituent  of  the  dietary,  since  the  mere  distension 
of  the  stomach  staves  off  hunger.  The  total  heat  value  of  the  food 
must  be  reduced  gradually.  Carbo-hydrates  must  be  largely  excluded, 
and  also  fats,  although  a  certain  amount  of  fat,  say  in  the  form  of 
butter,  is  permissible  and  even  beneficial  as  aiding  in  the  passage  of 
the  food  along  the  digestive  tube.  Alcoholic  beverages  are  in  general 
contra-indicated,  because  alcohol,  as  an  easily  oxidizable  substance, 
protects  the  carbo-hydrates  and  fats  from  oxidation,  and  perhaps  also 
because  the  normal  oxidative  power  of  the  tissues  may  be  depressed  by 
its  habitual  use.  On  the  other  hand,  tobacco  smoking,  which  has  some 
power  of  inhibiting  the  gastric  hunger  contractions,  may  be  permitted. 
Muscular  exercise,  cold  baths,  light  clothing  both  during  the  day  and 
at  night,  and  a  cool  environment,  are  favourable  to  the  reduction  of 
fat  by  increasing  the  consumption  of  material  and  the  loss  of  heat, 
just  as  a  sedentary  life  in  an  overheated  house  in  a  person  predisposed 
to  obesity,  and  eating  too  much  for  his  requirements,  favours  the 
putting  on  of  fat.  But  if  the  appetite  of  the  patient  is  allowed  to 
govern  the  intake  of  food,  the  increased  decomposition  brought  about 
by  exercise,  etc.,  is  very  likely  to  be  balanced  by  an  increased  ingestion, 
and  no  progress  will  be  made. 

Metabolism  of  Sterins  or  Sterols. — It  has  been  previously  stated 
that  cholesterin  appears  to  be  the  only  representative  of  the  sterins 
in  the  higher  animals.  Its  source  and  function  have  been  much 
discussed  of  late  years.  As  to  its  source,  there  seems  to  be  no 
reason  to  believe  that  any  part  of  the  cholesterin  of  the  tissues  is 
formed  from  decomposition  products  of  ordinary  fats,  carbo- 
hydrates, or  proteins.  It  is  probably  entirely  derived  from  the 
cholesterins  of  animal,  and  the  ph3rtosterins  of  vegetable  food.  On 
this  assumption,  its  metabolism,  unlike  that  of  the  great  groups  of 
food  substances,  is  carried  on  in  a  closed  circuit.  Evidence  that 
it  can  be  synthesized  from  other  substances  in  the  body  is  lacking. 
No  increase  in  the  cholesterin  has  been  observed  during  the  develop- 
ment of  eggs,  and  the  cholesterin  content  of  growing  chickens 
appears  to  correspond  to  the  sterins  taken  in  the  food  (Gardner). 
The  portion  of  the  cholesterin  which  is  ingested  in  the  form  of  esters 

36 


562  METABOLISM,  NUTRITION  AND  DIETETICS 

is  probably  split,  with  liberation  of  the  fatty  acid,  in  the  course  of 
digestion.  But  if  this  be  so,  cholesterin  esters  are  again  formed 
in  the  tissues,  for  the  cells  and  the  blood  contain  both  cholesterin 
esters  and  free  cholesterin.  While  some  cholesterin  is  excreted  in 
the  faeces  (p.  419),  there  is  evidence  that  a  portion  of  the  cholesterin 
of  the  bile  may  be  reabsorbed,  a  '  circulation  '  of  cholesterin  taking 
place  analogous  to  the  circulation  of  bile-salts.  The  appearance  of 
cholesterin  in  the  bile  has  been  connected  by  some  writers  with  the 
destruction  of  erythrocytes  in  the  liver,  or  the  conveyance  of  the 
products  of  their  decomposition  to  that  organ  (p.  21),  but  there 
are  no  means  of  distinguishing  between  the  cholesterin  set  free  from 
blood-corpuscles  and  that  liberated  from  other  cells.  Since  it  is 
contained  in  all  cells,  every  cell  may  be  supposed  to  contribute 
something  from  time  to  time  to  the  cholesterin  excretion. 

As  to  the  office  of  the  tissue-cholesterin,  it  can  only  be  suggested 
that  a  substance  so  ubiquitous  must  be  important.  There  is  some 
evidence  that  cholesterin,  free  or  combined,  plays  a  part  in  con- 
ferring on  the  cells  those  peculiarities  in  their  permeability  upon 
which  their  functions,  and  indeed  their  integrity,  depend.  Free 
cholesterin,  for  instance,  hinders  the  haemolytic  action  of  the 
saponins  (p.  28),  apparently  by  forming  compounds  with  them 
Whether  it  or  its  esters  are  actually  concentrated  at  the  surface  of 
the  cell,  and  contribute  to  the  formation  there  of  the  so-called 
'  lipoid  '  envelope,  is  not  definitely  known,  although  there  are  facts 
in  favour  of  this  idea. 

Metabolism  of  Phosphatides. — The  lecithins,  which  are  the  best- 
known  members  of  this  class  of  compounds,  have  been  already 
described  (p.  360).  They  are  built  up  of  glycerin,  fatty  acids, 
phosphoric  acid  in  the  form  of  glyceryl-phosphoric  acid,  and  a 
nitrogenous  base  cholin.  There  is  some  reason  to  think  that  the 
lecithins  of  the  tissues  are,  in  part  at  least,  not  free,  but  combined 
with  proteins  or  with  carbo-hydrates.  Other  bodies  belonging  to 
the  phosphatide  group  are  kephalin,  a  constituent  of  nervous  tissue 
and  of  yolk  of  egg,  cuorin  found  in  heart  muscle,  etc. 

It  is  probable,  as  stated  in  the  chapter  on  Digestion,  that  the 
phosphatides  of  the  food  are  hydrolysed  in  the  alimentary  canal 
with  liberation  of  the  glycerin,  fatty  acids,  and  the  other  com- 
ponents. It  is  not  known  whether  they  are  resynthesized  in  the 
intestinal  wall,  but  it  is  more  probable  that  they  pass  directly  to 
the  tissues,  where  they  can  be  utilized  for  building  up  the  phos- 
phatides of  the  cells.  Cholin  is  found  in  small  quantities  free  in  the 
tissues,  and  also,  it  is  said,  in  the  blood-plasma.  Glyceryl-phos- 
phoric acid  has  also  been  obtained  in  small  amount  from  various 
tissues.  The  other  components  of  lecithin  are,  of  course,  never 
wanting,  and  there  can  be  no  doubt  that  the  cells  possess  the  power 
of  reconstructing  phosphatides  from  such  materials.     They  can  do 


METABOLISM  OF  PROTEINS  563 

more  than  this:  they  can  prepare  the  'building-stones  'themselves. 
For  even  when  the  ingestion  of  phosphatides  in  the  food  is  excluded, 
or  the  intake  is  so  small  as  to  be  negligible,  the  formation  of  phos- 
phatides in  the  body  goes  on  apparently  witliout  check.  An  instance 
of  this  will  be  given  on  a  future  page  in  discussing  experiments  on 
the  relative  value  of  different  proteins  for  nutrition  and  growth. 
A  very  striking  observation  has  been  recorded  by  McCoUom,  who 
fed  three  hens  on  a  diet  almost  free  from  fat.  In  about  three  and  a 
half  months  they  laid  fifty-seven  eggs,  containing  over  9  per  cent,  of 
phosphatides.  Calculation  showed  that  here,  first  of  all,  fats  or  their 
components  must  have  been  constructed  from  carbo-hydrates. 
Then  the  nitrogenous  component  of  the  phosphatides  (cholin  in  the 
case  of  lecithin,  at  least)  must  have  been  obtained  from  some  source, 
possibly  from  an  amino-acid  by  the  addition  of  methyl  groups 

/CH3 

(CH3),  of  which  chohn,  OH.H2C.H2C-N<^fj3  (trimethyl-oxyethyl- 

OH 
ammonium  hydroxide)  contains  three. 

Section  III. — Metabolism  of  Proteins. 

Blood-Proteins. — ^The  two  chief  proteins  of  the  plasma,  serum- 
globulin  and  serum-albumin,*  must,  as  has  been  already  pointed  out, 
be  recruited  from  proteins  absorbed  from  the  intestine  and  for  the  most 
part,  at  any  rate,  profoundly  altered  in  its  lumen  and  in  their  passage 
through  the  epithelium  which  lines  it.  Even  when  proteins  are  being 
actively  absorbed,  the  plasma,  after  the  blood-proteins  have  been 
separated,  contains  no  substances  which  give  the  biuret  reaction 
(p.  444).  So  that  the  peptones,  which  can  be  demonstrated  in  the 
intestinal  contents,  suffer  great  changes  before  or  during  their 
absorption.  The  physiological  reasons  for  this  alteration  are  in  a 
measure  known,  and  have  already  been  alluded  to  in  connection 
with  the  digestion  of  proteins.  No  doubt  the  far-reaching  decom- 
position of  the  protein  molecule  may  to  some  extent  facilitate  the 
absorption  of  protein  food.  No  doubt  also  it  is  imperative  that 
such  comparatively  slightly  hydrolysed  products  as  peptone,  and 
particularly  proteose,  should  not  appear  in  quantity  in  the  blood, 
for  when  injected  they  cause  profound  changes  in  that  liquid,  one 
expression  of  which  is  the  loss  of  its  power  of  coagulation,  and  are 
rapidly  excreted  by  the  kidneys,  or  separated  out  into  the  lymph. 
But  the  passage  of  the  food  from  the  stomach  is  so  gradual  an  affair, 
the  quantity  of  digesting  protein  present  at  one  time  in  any  loop 
of  intestine  is  so  small,  and  the  rush  of  blood  which  irrigates  the 

*  It  is  probable  that  plasma  contains  a  mixture  of  difierent  albumins  and 
globulins. 


564  METABOLISM.  NUTRITION  AND  DIETETICS 

active  mucosa  is  so  large,  that  the  concentration  of  peptone  or 
proteose  necessary  to  produce  injurious  effects  could  hardly  in  any 
case  be  realized.  Again,  there  is  no  evidence  that  the  simpler 
decomposition  products  of  further  hydrolysis  are  not  in  equal  con- 
centration as  poisonous  as  proteose  and  peptone. 

Apart  from  any  influence  which  it  may  have  in  favouring  absorp- 
tion, the  complete  shattering  of  the  protein  molecule  has  a  double 
significance.  In  the  first  place,  as  already  pointed  out,  the  food- 
proteins  cannot  be  used  directly  in  the  upbuilding  and  repair  of  the 
protoplasm  (p.  442),  since  the  tissue-proteins  differ  from  them  and 
from  each  other  in  the  amount  and  nature  of  the  amino-acids  and 
other  groups  in  their  molecule  (p.  2).  Secondly,  under  ordinary 
dietetic  conditions  a  surplus  of  nitrogen  in  the  protein  food  has  to 
be  got  rid  of  by  being  converted  into  urea  without  being  built  up 
into  the  tissue  substance.  Here  we  come  upon  the  fundamental 
fact  that  the  protein  katabolism  is  not  a  single  uniform  process. 
Two  forms  may  be  distinguished  which  are  essentially  independent 
in  course  and  character.  One  kind  varies  extremely  in  its  quantita- 
tive relations,  according  to  the  amount  of  protein  in  the  food.  Its 
chief  end-products  are  urea,  representing  the  nitrogen,  and  inorganic 
sulphates,  representing  the  sulphur  of  the  proteins.  Since  this  form 
of  katabolism,  as  we  shall  see  directly,  is  not  essentially  connected 
with  the  life  and  nutrition  of  the  living  substance,  it  is  termed 
exogenous.  The  other  variety  is  practically  constant  in  amount 
for  one  and  the  same  individual,  and  independent  of  the  quantity 
of  protein  in  the  food.  Its  characteristic  end-products  are  kreatinin 
and  neutral  sulphur.  This  form  of  protein  katabolism  is  essentially 
an  expression  of  the  waste  of  the  living  substance  itself,  and  is 
therefore  spoken  of  as  endogenous. 

Some  have  supposed  that  the  intestinal  mucosa  has  as  one  of  its 
special  functions  the  resynthesis  of  a  great  part  of  the  digestive 
decomposition  products  into  the  proteins  of  the  blood-plasma.  If 
this  is  the  case,  these  proteins  must  be  again  decomposed  in  the 
cells  of  the  various  tissues  in  order  that  the  '  building-stones  '  may 
be  recombined  to  form  the  tissue-proteins.  For  the  proteins  of  the 
organs  are  not  the  same  as  those  of  the  blood,  and  the  proteins  of 
different  organs  differ  characteristically  from  each  other.  The 
significance  of  the  synthetic  function  of  the  intestinal  wall  would 
then  lie  in  this:  that  from  the  varying  mixture  of  amino-acids,  etc., 
derived  from  the  food-proteins  an  always  uniform  and  suitable 
protein  mixture  (the  blood-proteins)  is  fabricated  for  the  feeding 
of  the  tissues.  Experiments  intended  to  test  this  hypothesis  have 
hitherto  yielded  a  negative  result.  No  accumulation  of  protein  in 
the  wall  either  of  the  intestine  in  situ  or  of  the  isolated  surviving 
intestine  has  been  detected  during  absorption  of  the  decomposition 
products  of  protein.     An  alternative  assumption,  and  superficially 


METABOLISM  OF  PROTEINS  565 

at  least  a  simpler  one,  is  that  no  more  extensive  synthesis  of  proteins 
occurs  in  the  wall  of  the  alimentary  canal  than  is  necessary  for  the 
needs  of  the  tissues  composing  it,  and,  perhaps  in  addition,  for  the 
maintenance  of  the  normal  composition  of  the  plasma,  and  that  the 
decomposition  products  of  the  proteins  are  mainly  absorbed  as  such, 
and  pass  in  the  blood  to  the  tissues  for  which  they  are  destined.     If 
this  is  the  case,  the  blood-proteins  can  no  longer  be  looked  upon  as 
representing  the  main  current  of  protein  supply  for  the  organs,  but 
rather  the  store  of  protein  material  proper  to  the  circulating  tissue 
blood  itself,  and  which  confers  on  it  certain  chemical  and  physico- 
chemical  properties  {eg.,  the  due  degree  of  viscosity)  necessary  for 
its  function.     Slowly  accumulated,  under  ordinary  conditions,  and 
slowly  consumed,  this  protein  store  may,  of  course,  be  at  the  dis- 
posal of  the  organs  in  an  emergency — for  instance,  in  starvation — 
or   may  be  rapidly  recruited   from  the   organ-proteins,   as  after 
haemorrhage,  just  as  in  prolonged  hunger  the  proteins  of  skeletal 
muscle  may  be  utilized  to  feed  the  heart.     That  the  blood-proteins 
can  serve  as  nutritive  material  for  the  cells  without  undergoing 
digestion  in  the  alimentary  canal  is  well  shown  by  the  observations 
of  Carrel  and  Burrows  on  the  growth  of  isolated  tissues  in  a  medium 
composed  of  clotted  blood-plasma.     But,  as  previously  pointed  out 
in  another  connection  (p.  444),  a  portion,  and  probably  a  large 
portion,  of  the  digested  protein  is  absorbed  from  the  intestine  by 
the  blood  in  the  form  of  amino-acids.     Considerable  quantities  of 
these  compounds  can  be  separated  by  dialysis  from  blood  drawn 
off  during  the  absorption  of  proteins  or  by  the  process  of  vivi- 
diffusion    (p.    48)    (Abel).      Among    these  amino-acids,   gljxocoll, 
alanin,  glutaminic  acid,  and  leucin,  have  been  identified.     While 
the  quantity  of  amino-acids  in  the  blood,  which  is  very  small  in  the 
fasting  animal,  is  decidedly  increased  during  protein  digestion,  it 
is  probable  that  even  in  starvation  amino-acids  derived  from  the 
decomposition  of  the  body-proteins  are  not  entirely  lacking.     It 
has  been  surmised  that  they  constitute  the  form  in  which  proteins 
are  transported  from  tissue  to  tissue,  as  well  as  the  form  in  which 
proteins  are  normally  utilized  by  the  cells.     Although  this  cannot 
be  regarded  as  yet  established,  there  is  reason  to  believe  that  the 
amino-acids  play  a  great  part  in  protein  metabolism,  perhaps  as 
great  a  part  as  the  dextrose  does  in  the  metabolism  of  the  carbo- 
hydrates.    There  is  some  evidence  that  serum-albumin  is  more 
directly  related  to  the  proteins  of  the  food  than  serum-globulin. 
And  it  is  said  that   during  starvation  the  albumin  is  relatively 
diminished,  and  the  globulin  relatively  increased.     It  is,  of  course, 
not  at  all  improbable  that  the  plasma-proteins  have  a  double  source 
— organ-proteins  on  the  one  hand,  food-proteins  on  the  other.     In 
any  case,   it   is  certain  that   serum-albumin  and  serum-globulin 
cannot  be  interchangeable  without  far-reaching  decomposition,  for 


566 


METABOLISM,  NUTRITION  AND  DIETETICS 


their  composition  is  very  different.  The  globuHn,  e.g.,  yields  glyco- 
coll,  but  the  albumin  does  not.  That  the  plasma-protein  mixture 
maintains  a  very  constant  composition  in  the  face  of  wide  variations 
in  the  composition  of  the  food-protein  is  indicated  by  the  following 
experiment : 

A  horse  fed  mainly  on  hay  and  oats  was  bled  to  the  amount  of 
6  litres,  and  in  the  total  protein  of  the  serum  the  content  of  tyrosin  and 
glutaniinic  acid  was  determined.  In  order  to  eliminate  the  influence 
of  remains  of  the  food  in  the  digestive  canal,  nothing  was  given  to  the 
animal  for  a  week.  Then  6  litres  of  blood  were  again  removed,  and  the 
tyrosin  and  glutaniinic  acid  in  the  serum-protein  again  estimated. 
The  horse  was  now  fed  with  gliadin  (one  of  the  prolamins  or  alcohol- 
soluble  proteins  obtained  from  flour),  a  substance  which  contains  36-5  per 
cent,  glutaminic  acid  and  2-37  per  cent,  tyrosin — that  is,  about  the 
same  amount  of  tyrosin  as  the  serum-protein,  but  about  four  times  as 
much  glutaminic  acid.  The  serum-protein  was  again  analyzed  for  the 
two  amino-acids  after  this  diet.  The  results  of  one  experiment  are 
shown  in  the  table  : 


Normal. 

After  8  Days' 
Hunger. 

After  Feeding 

with  1,500 

Grammes 

Gliadin. 

After  Feeding 

again  with  1,500 

Grammes 

Gliadin. 

Tyrosin  -         -         - 
Glutaminic  acid 

2-43 
8-85 

2 '60 
8-20 

2*24 

7-88 

2-52 

8-25 

No  increase  in  the  glutaminic  acid  content  of  the  serum-protein 
occurred,  although,  owing  to  the  loss  of  blood,  much  new  serum-protein 
must  have  been  formed.  If  the  amino-acids  of  the  gliadin  were  used 
without  change  to  build  up  the  new  serum-protein,  three-quarters  of 
the  glutaminic  acid  must  have  been  superfluous,  and  the  nitrogen  of 
this  portion  may  have  been  straightway  changed  into  urea  and  excreted. 
But  the  possibility  that  the  glutaminic  acid,  or  a  portion  of  it,  may 
have  been  changed  into  other  amino-acids  in  the  body  cannot  be 
excluded.  In  the  case  of  some  of  the  amino-acids  it  has  been  shown 
that  such  a  transformation  occurs  (p.  602)  (Abderhalden). 

The  high  degree  of  independence  of  the  food  and  body  proteins  is 
still  more  clearly  exhibited  in  the  table  from  Abderhalden  on  p.  567, 
in  which  the  proteins  of  milk  are  compared  with  some  of  the  proteins 
which  must  be  formed  from  them  in  the  body  of  the  suckling.  The 
numbers  represent  percentages  of  the  weight  of  each  protein. 

Living  and  Dead  Proteins. — Carried  to  the  tissues,  the  decomposition 
products  of  the  food-proteins,  or  the  regenerated  proteins  of  the  plasma, 
which  in  ordinary  language  are  still  to  be  regarded  as  dead  material, 
are  built  up  into  the  living  protoplasm,  at  any  rate  to  the  extent  neces- 
sary to  make  good  its  waste.  In  this  form  they  sojourn  for  a  time 
within  the  cells,  and  then  they  become  dead  material  again.  The 
nature  of  this  tremendous  transformation  has,  of  course,  been  the 
subject  of  speculation,  but  the  truth  is  that  we  do  not  understand 
wherein  the  difference  between  a  living  and  a  dead  cell,  between  a  living 
and  a  dead  particle  in  one  and  the  same  cell,  really  consists.     All  we 


METABOLISM  OF  PROTEINS 


5f^7 


know  is  that  now  and  again  a  protein  molecule  or  an  aggregate  of  such 
molecules  incorporated  in  the  colloid  mass  which  constitutes  the  proto- 
plasm of  a  muscle-fibre,  or  a  gland-cell,  or  a  nerve-cell,  must  fall  to 
pieces.  Now  and  again  a  molecule  of  protein ,  hitherto  dead  (or  perhaps, 
to  speak  moBc  correctly,  liitlierto  not  a  constituent  of  living  protoplasm, 
since  protoplasm  is  certainly  more  than  protein),  or  a  molecule  of  a 
particular  amino-acid,  or  perhaps  a  polypeplide  group  intermediate  in 
complexity  between  amino-acid  and  protein,  coming  within  the  grasp 
of  the  molecular  forces  or  chemical  affinities  of  the  living  substance,  is 
caught  up  by  it,  takes  on  its  peculiar  motions,  acquire  s  its  special  powers, 
and  is,  as  we  phrase  it,  made  alive.  Each  cell  has  the  power  of  selecting 
and,  if  necessary,  further  decomposing  or  further  synthesizing  the 
protein  materials  offered  to  it;  so  that  a  particle  of  scrum-albumin  or  a 
mixture  of  amino-acids  may  chance  to  take  its  place  in  a  liver-cell  and 
help  to  form  bile,  while  an  exactly  similar  particle  or  mixture  may 
furnish  constituents  to  an  endothelial  scale  of  a  capillary  and  assist  in 
forming  lymph,  or  to  a  muscular  fibre  of  the  heart  and  help  to  drive  on 
the  blood,  or  to  a  spennatozoon  and  aid  in  transferring  the  peculiarities 
of  the  father  to  the  offspring.  And  just  as  a  tomb  and  a  lighthouse,  a 
palace  and  a  church,  may  be,  and  have-been,  built  with  the  same  kind 
of  material,  or  even  in  succession  with  the  very  same  stones,  so  every 
organ  builds  up  its  own  characteristic  structure  from  the  common 
quarry  of  the  blood . 


1 

! 

c 

u 

.   d 

< 

Serum- 
Globulin. 

c 
0 

5 

.5 

ft 

1 

2 

Glycocoll  - 

o 

0 

0 

3-5 

0 

3-0 

0'5 

26-0 

47 

Alanin 

0-9 

2-5 

2-7 

2-2 

4-2 

3-6 

3-5 

6-6 

1-5 

Valin 

I'O 

0'9 

some 



some 

I-o 

— 

I-o 

0-9 

Leucin 

10-5 

19-5 

20 -o 

18.7 

29-0 

15-0 

1^8 

21-4 

7-1 

Serin 

0-2 

— 

0-6 



0-6 

some 

— 

— 

Cystin 

0-07 

— ■ 

2-3 

0-7 

0-3 



— 

0-6 

Asparaginic  acid 

1-2 

i-o 

3-1 

2-5 

4-4 

2-0 

— 

— 

lO-O  1 

Glutaminic  acid 

II-O 

lo-o 

7-7 

8-5 

1-7 

8-0 

0-5 

0-8 

3-7 

Lysin 

5-8 

— 

4-3 

— 

6-9 

— 

Arginin 

4-8 

— 

—  ■ 

— 

5-4 

— 

15-5 

0-3 

— 

Phenylalanin      - 

3-^ 

2-4 

3-1 

3-8 

4-2 

2-0 

2-2 

3-9 

— 

Tyrosin      - 

4-5 

I-o 

2-1 

2-5 

1-5 

3-5 

5-2 

0-34 

3-2  , 

Prolin 

3-1 

4-0 

I-O 

2-8 

2-3 

2-5 

1-5 

1-7 

3-4 

Histidin    - 

2-6 

I  I-o 

1-5 

1 

It  is  not  any  difference  in  the  kind  of  protein  offered  them  which 
determines  the  difference  in  structure  and  action  between  one  organ 
and  another.  In  this  quarry  alongside  of  the  plr.sma  proteins  the  tissue 
cells  find  what  is  probably  more  important  for  their  individual  nutrition, 
the  building-stones  of  the  shattered  food-protein  molecules.  They  are 
only  under  exceptional  circumstances  confronted  with  intact  molecules 
of  food -proteins.  '  The  body  cells  do  not  know  what  the  kind  of  food 
was  '  (Abdcrhalden).  In  the  case  of  the  more  highly  developed  tissues, 
at  least,  no  mere  change  of  food  will  radically  alter  the  structure  of  the 
cells,  nor  even,  as  we  have  seen,  the  composition  of  the  tissue  proteins. 
A  cell  may  be  fed  with  different  kinds  of  food,  it  may  be  overfed,  it  may 


568  METABOLISM.  NUTRITION  AND  DIETETICS 

be  ill-fed,  it  may  be  starv^ed;  but  its  essential  peculiarities  remain  as 
long  as  it  continues  to  live.  What  may  be  called  its  organization,  per- 
haps at  bottom  a  more  or  less  metaphorical  expression  for  its  essential 
physico-chemical  make-up,  dominates  its  nutrition  and  function. 

'  We  must  assume  that  many  of  the  enigmatical  properties  of  living 
matter  depend  upon  the  activity  of  intact  protein  molecules.  We  can 
obtain  some  idea  of  the  possible  variety  in  the  combinations  of  the 
''  building-stones  "  of  the  proteins  by  recalling  the  fact  that  they  are  as 
numerous  as  the  letters  of  the  alphabet,  which  are  capable  of  expressing 
an  infinite  number  of  thoughts.  Every  peculiarity  of  species  and  every 
occurrence  affecting  the  individual  may  be  indicated  by  special  com- 
binations of  the  "building-stones" — that  is  to  say,  by  specific  proteins. 
Consequently  we  may  readily  understand  how  peculiarity  of  species 
may  find  expression  in  the  chemical  nature  of  the  proteins  constituting 
living  matter,  and  how  they  may  be  transmitted  through  the  materi?! 
contained  in  the  generative  cells  '  (Kossel).  Add  to  the  great  variety 
of  compounds  rendered  possible  by  the  enormous  number  of  permuta- 
tions and  combinations  of  the  protein  '  building-stones,'*  the  still  greater 
variety  rendered  possible  by  the  fact  that  the  quantitative  relations  of 
given  amino-acids  may  vary  greatly  in  different  proteins,  and  it  will  be 
seen  what  a  practically  infinite  power  of  functional  adjustment  and 
reaction,  correlated  with  a  practically  infinite  variety  of  chemical 
changes  in  the  midst  of  which  the  cell  still  preserves  its  specificity 
through  and  through,  may  be  conferred  upon  the  living  substance  by 
its  content  of  protein. 

Some  have  supposed  that  the  protein  of  the  living  substance  is  es- 
sentially different  from  dead  protein,  especially  in  possessing  a  character- 
istic instability,  a  prodigious  power  of  dissociation  and  reconstruction. 
All  the  older  theories  which  attempted  to  explain  this  alleged  difference 
require  rcjvision  in  accordance  with  the  newer  chemistry  of  proteins, 
and  speculations  on  the  subject  are  probably  in  any  case  premature 
till  the  constitution  of  the  proteins  is  thoroughly  understood.  In  the 
meantime  it  is  enough  to  say  that  the  velocity  of  the  reactions  into 
which  the  proteins  of  living  protoplasm  or  their  constituent  amino- 
acids  may  enter  must  depend  upon  intracellular  conditions,  which  may 
vary  rapidly  and  within  wide  limits.  For  example,  enzymes  may  be 
present  m  greater  or  smaller  concentration,  or  be  activated  and  aided 
more  or  less  powerfully  by  other  substances,  or  by  a  more  or  less  favour- 
able chemical  reaction  of  the  medium.  The  protein  itself,  too,  or  such 
part  of  it  as  is  ready  for  decomposition,  ma^^  exist  in  a  physical  con- 
dition now  more  and  again  less  favourable  to  the  attack  of  the  enzymes. 
It  may  not  be  superfluous  at  this  point  to  again  warn  the  reader  that 
protoplasm  and  tissue -proteins  are  by  no  means  synonymous.  The 
physical,  phj-sico-chemical,  and  chemical  changes  involved  in  the 
katabolism  of  the  colloid  aggregates,  including  water,  salts,  phosphatides, 
sterins,  and  probably  fats  and  dextrose  as  well  as  proteins,  to  which 
the  term  protoplasm  is  applied,  may  be  many  and  complex  before  the 
individual  proteins  known  to  the  chemist  come  face  to  face  in  the 
interior  of  the  cells  with  the  ferments  which  decompose  them.  On  the 
other  hand,  it  has  not  been  proved  that  in  the  katabolic  processes  of  the 
living  substance  isolated  proteins  ever  form  a  stage.  It  may  well  be 
that  without  the  complete  decomposition  of  the  protein  molecules,  or 

*  Twenty  different  amino-acids,  each  used  only  once,  but  in  a  elifferent  order, 
would  be  capable  of  forming  about  2,000,000,000,000,000,000  (two  thousand 
million  times  a  thousand  millions)  of  different  polypeptides,  all  containing  the 
various  amino-acids  in  the  same  proportions  (Abderhalden). 


METABOLISM  OF  PROTEINS  569 

even  without  their  complete  detachment  from  the  protoplasm,  indi- 
vidual amino-acids  or  mixtures  of  amino-acids,  or  polypeptide  groups, 
are  cut  out  of  the  protoplasmic  mass. 

It  is  now  necessary  to  follow,  as  far  as  is  possible,  the  steps 
in  the  degradation  of  the  body-proteins.  Since  there  is  reason  to 
believe  that  these,  like  the  food-proteins,  are  first  split  up  into  the 
amino-acids  from  which  they  were  originally  synthesized  before 
undergoing  further  decomposition,  a  study  of  protein  metabolism 
is  to  a  great  extent  a  study  of  the  metabolism  of  amino-acids.  In 
this  study  it  is  for  most  purposes  impracticable,  even  if  it  were 
desirable,  to  distinguish  between  amino-acids  directly  derived  from 
the  food,  and  which  have  not  yet  been,  and  may  never  be,  built  up 
into  tissue-proteins,  and  those  derived  from  the  tissue  proteins. 
There  is  nothing  to  indicate  that  the  fate  of  a  given  amino-acid, 
once  it  has  reached  the  blood,  depends  in  the  least  upon  its  source. 
It  may  be  said  at  once  that  the  katabolism  of  the  amino-acids  is  not 
a  single  and  uniform  process,  one  step  in  which  inevitably  follows 
another  till  the  final  end-products  are  reached.  On  the  contrary, 
certain  of  the  stages  may  become  the  starting-points  of  syntheses, 
which  may  lead  back  to  the  original  or  to  another  protein,  or  it 
may  be  to  sugar  or  to  fat.  The  extent  of  such  synthesis,  and 
even  in  some  degree  the  stage  from  which  it  starts,  may  be  assumed 
to  depend  upon  the  needs  of  the  tissues  and  the  relative  abundance 
of  protein  and  of  other  foods. 

Formation  of  Amino-Acids  from  Tissue-Proteins. — That  amino- 
acids  are  formed  in  the  metabolism  of  the  cells  and  by  the  action  of 
intracellular  enzymes  is  indicated  by  the  fact  that  proteol\i:ic  en- 
zymes (proteases)  are  invariably  present  in  the  tissues,  and  can 
be  obtained  from  them  by  appropriate  methods — e.g.,  by  subjecting 
the  organ  in  a  finely  divided  state  to  a  high  pressure  and  collecting 
the  expressed  juice.  Not  only  do  unicellular  organisms,  like  leuco- 
cytes, yeast  cells,  and  bacteria,  which  must  naturally  depend  upon 
themselves  alone  for  all  enzymatic  reactions,  yield  ferments  which 
have  the  power  of  splitting  proteins,  peptones,  and  polypeptides 
into  amino-acids,  but  their  existence  has  been  demonstrated  in 
practically  all  the  organs  of  the  higher  animals  and  man.  When  a 
piece  of  liver,  e.g.,  is  removed  with  aseptic  precautions  and  kept  at 
body-temperature,  extensive  auto-digestion  occurs,  and  ammonia 
and  other  basic  substances,  glycin,  and  tryptophane,  appear  among 
the  products.  Tyrosin  appears  so  early  that  it  is  scarcely  possible 
to  doubt  that  it  must  be  a  product  of  protein  decomposition  in  the 
liver-cells  under  normal  conditions — a  decomposition  which  could 
be  observed  also  in  the  organ  hi  situ  were  the  circumstances  as 
favourable.  The  circumstances  are  less  favourable  in  an  organ 
whose  circulation  is  going  on.  because  the  amino-acids  are  removed 
by  the  blood  as  they  are  formed.     Further,  it  is  to  be  assumed  that 


570  METABOLISM,  NUTRITION  AND  DIETETICS 

the  regulation  of  the  ferment  action,  which  is  a  characteristic 
property  of  the  normal  cell,  becomes  feebler  the  longer  it  is  with- 
drawn from  normal  conditions.  Similar  autolytic  processes  have 
been  observed  in  the  spleen,  muscle,  lymph-glands,  kidneys,  lungs, 
stomach  wall  (independently  of  pepsin),  thymus,  and  placenta; 
also  in  pathological  new  growths  like  carcinoma,  in  the  breaking 
down  of  which  and  in  the  removal  of  such  exudations  as  occur  in 
the  alveoli  in  pneumonia,  these  proteolytic  ferments  seem  to  play 
a  part.  It  is  to  be  assumed  that  the  syntheses  of  the  proteins  or 
their  products,  which  are  scarcely  less  characteristic  of  the  tissue 
cells  than  the  decompositions  effected  by  them,  are  also  due  to 
the  action  of  separate  intracellular  ferments  or  upon  the  reversed 
activity  of  the  proteolytic  ferments. 

More  direct  proofs  of  the  production  of  amino-acids  in  the  tissues 
are  not  lacking.  A  rare  condition  known  as  cystinuria  has  been 
alluded  to  on  a  previous  page  (p.  482).  Here  there  is  a  continuous 
excretion  of  the  sulphur-containing  amino-acid  cystin  in  the  urine. 
Sometimes  the  cystin  is  accompanied  by  other  amino-acids,  as 
leucin  and  tyrosin,  a  condition  which  might  be  called  amino- 
aciduria. Cystinuria,  while  of  course  resulting  from  a  gross  anomaly 
in  metabolism,  is  of  little  clinical  importance  unless  the  sparingly 
soluble  cystin  should  form  calculi  somewhere  in  the  urinary  tract. 
The  most  plausible  explanation  of  the  condition  is  that  in  the 
normal  course  of  the  metabolism  each  of  the  '  building-stones  '  of 
the  proteins  is  sooner  or  later  further  decomposed  by  special  fer- 
ments, and  that  for  some  reason  the  ferment  which  acts  on  cystin 
is  absent,  or  if  it  is  still  produced,  the  conditions  are  more  or  less 
unfavourable  to  its  action.  Unable  to  take  its  place  in  the  meta- 
bolic current,  except  in  so  far  as  it  can  be  utilized  to  form  taurin, 
and  therefore  taurocholic  acid — for  this  property  it  has  not  lost — 
cystin  becomes  a  chemical  outcast  in  the  body  of  the  cystinuric 
individual,  and  is  got  rid  of  by  the  kidneys  as  an  '  unemployable.' 
By  comparing  the  amount  of  cystin  excreted  with  the  amount 
ingested  in  the  food-proteins  and  with  the  (undiminished)  amount 
contained  in  the  tissues  (especially  the  hair  and  the  nails,  since 
keratin  is  exceptionally  rich  in  cystin),  it  has  been  shown  that  a 
portion  of  the  cystin  in  the  urine  must  have  come  from  the  tissues 
(Abderhalden).  Observations  on  animals  in  prolonged  starvation 
afford  additional  evidence.  The  hair  and  nails  continue  to  grow 
and  to  maintain  the  high  cystin  content,  and  taurocholic  acid  con- 
tinues to  be  excreted.  In  like  manner  glycin  continues  to  be  pro- 
duced and  to  unite  with  cholic  acid  to  form  the  glycocholic  acid  of 
the  bile. 

There  are  other  and  more  striking  proofs  that  glycin  can  be 
formed  in  the  body  in  large  amount.  For  example,  as  already 
stated  (p.  475),  when  benzoic  acid  is  ingested  it  is  not  excreted  as 


METABOLISM  OF  PROTEINS  571 

such  in  the  urine,  but  coupled  with  glycocoll  as  hippuric  acid. 
Thus— 

CjHfi.COOH  +  CH2(NH2).COOH  -  HgO  =C8H6.CO.NH.CH2.COOH 

Benzoic  acid.  Glycocoll.  Hippuric  acid. 

Benzoic  acid,  therefore,  meets  glycin  in  the  body,  and  combines 
with  it,  as  fatty  acids  meet  glycerin  and  combine  with  it.  Even 
starving  animals  fed  with  benzoic  acid  excrete  large  quantities  of 
hippuric  acid.  Yet  their  tissues,  as  shown  by  analysis  after  death, 
yield  as  much  glycocoll  as  starving  animals  which  have  received  no 
benzoic  acid,  and  excreted  little  or  no  hippuric  acid.  Many  other 
acids  which  are  totally  foreign  to  the  body  are,  when  ingested, 
paired  in  the  same  way  with  glycocoll  and  excreted  in  the  urine. 
Even  substances  whose  chemical  nature  does  not  permit  of  a  direct 
union  with  the  glycin  are  often  altered  by  oxidation  or  reduction 
till  they  can  unite  with  it,  and  then  the  coupling  takes  place,  and 
the  conjugated  acid  is  eliminated  by  the  kidneys.  The  paired  or 
aromatic  sulphuric  acid  which  we  have  already  recognized  as  a 
normal  constituent  of  the  vuine  affords  another  instance  of  this 
coupling.  Cystein  among  the  derivatives  of  proteins,  and  glycu- 
ronic  acid  (p.  476)  among  the  derivatives  of  carbo-hydrates,  can 
also  unite  in  the  same  way  with  numerous  compounds.  There  is 
some  evidence  that  the  physiological  significance  of  this  process  is 
that  the  toxicity  of  the  foreign  substances,  or,  as  in  the  case  of  the 
aromatic  sulphuric  acid  of  the  urine,  of  substances  formed  by 
bacteria  in  the  intestine,  or  even  produced  in  the  metabolism  of  the 
tissues,  is  diminished  by  the  pairing. 

The  place  and  manner  of  formation  of  hippuric  acid  have  been 
investigated  with  the  following  result:  If  an  excised  kidney  is  per- 
fused with  blood  containing  benzoic  acid,  or,  better,  benzoic  acid 
and  glycin,  hippuric  acid  is  formed.  Oxygen  is  required,  for  if  the 
blood  is  saturated  with  carbon  monoxide,  or  if  serum  is  employed 
for  perfusion,  the  synthesis  does  not  take  place.  The  kidney  cells 
must  be  intact,  for  if  a  mixture  of  blood,  glycin,  and  benzoic  acid 
be  added  to  a  minced  kidney  immediately  after  its  removal  from 
the  body,  hippuric  acid  is  produced,  but  not  if  the  kidney  has  been 
crushed  in  a  mortar.  Nevertheless,  there  is  some  evidence  that  a 
ferment  is  concerned,  and  the  known  mechanism  of  similar  reactions 
in  the  body  scarcely  permits  the  physiologist  to  acquiesce  in  anv 
other  explanation.  It  must  not  be  forgotten  that  the  urinary 
constituents  which  must  come  into  contact  with  the  ferment  when 
the  kidney  is  crushed  may  injure  or  inhibit  the  enzyme.  In 
herbivora  hippuric  acid  cannot  normally  be  detected  in  the  blood; 
'it  is  present  in  large  quantities  in  the  urine;  it  must  therefore  be 
manufactured  in  the  kidney,  not  merely  separated  by  it.  In  certain 
animals,  as  the  dog,  the  kidney  is  the  sole  seat  of  the  production 


572  METABOLISM,  NUTRITION  AND  DIETETICS 

of  hippuric  acid.  But  in  the  rabbit  and  the  frog  some  of  it  must 
also  be  formed  in  other  tissues,  for  after  extirpation  of  the  kidneys 
the  administration  of  benzoic  acid  causes  hippuric  acid  to  appeal 
in  the  blood.  It  has,  indeed,  been  recently  shown  that  when  the 
rabbit's  liver  is  perfused  with  blood  containing  benzoic  acid,  hip- 
puric acid  is  produced.  The  benzoic  acid  required  for  the  normal 
excretion  of  hippuric  acid  comes  mainly  from  substances  of  the 
aromatic  group  contained  in  vegetable  food,  but  a  small  amount  is 
produced  in  the  body,  since  hippuric  acid  does  not  entirely  dis- 
appear from  the  urine  in  starvation. 

The  differences  which  may  exist  in  the  metabolism  of  different 
groups  of  animals  is  well  illustrated  by  the  fact  that  in  birds,  when 
benzoic  acid  is  given  in  the  food,  it  unites  not  with  glycin,  but  with 
ornithin,  a  derivative  of  arginin,  forming  not  hippuric  acid,  but 
ornithuric  acid  (dibenzoyl-ornithin).  A  much  more  important 
instance  of  such  a  difference  will  be  seen  when  we  come  to  consider 
the  formation  of  urea  and  uric  acid. 

The  method  by  which  the  presence  and  the  production  of  glyco- 
coll  in  the  body  are  demonstrated  by  coupling  it  with  benzoic  acid, 
and  so  saving  it  from  decomposition  and  bringing  it  to  excretion, 
can  also  be  applied  to  other  amino-acids.  If  instead  of  fishing 
with  the  bait  benzoic  acid  we  fish  with  a  bait  called  brom-benzol 
(CgHg.Br)  (or  bromo-benzene),  a  substance  derived  from  benzol  by 
the  substitution  of  an  atom  of  bromine  for  an  atom  of  hydrogen), 
we  capture  the  amino-acid  cystein  in  the  form  of  a  compound 
called  mercapturic  acid,  produced  by  the  union  of  brom-benzol  with 
cystein  and  acetic  acid,  with  oxidation  and  loss  of  water.  In  other 
words,  when  this  substance  is  administered,  mercapturic  acid  is 
excreted  in  the  urine,  the  cystein,  which  is  very  unstable  and  readily 
changes  into  cystin  (p.  354),  being  thus  preserved  from  decom- 
position. Another  instance  in  which  amino-acids  (t57rosin:  and 
phenylalanin),  which  would  normally  be  decomposed  and  so  escape 
detection,  come  to  the  surface  by  being  excreted  in  the  urine,  has 
already  been  alluded  to  in  connection  with  alkaptonuria  (p.  477). 
In  this  condition,  which  seems  to  have  no  serious  significance  so 
far  as  the  well-being  of  the  patient  is  concerned,  not  only  does  the 
taking  of  food  containing  the  aforesaid  amino-acids  lead  to  an 
increased  excretion  of  homogentisinic  acid,  but  even  in  starvation 
this  substance  still  continues  to  appear  in  the  urine.  Since  homo- 
gentisinic acid  is  undoubtedly  formed  from  tyrosin  and  from  phenyl- 
alanin, this  observation  constitutes  a  convincing  proof  that  these 
amino-acids  are  produced  from  tissue-proteins. 

Fate  of  Amino-Acids  in  the  Body. — The  problem  of  the  katabol- 
ism  of  proteins  is  thus  reduced  to  the  question.  What  becomes  of 
the  amino-acids  ?  Where,  how,  by  what  stages,  and  to  what  end- 
products  are  they  decomposed  ?    As  to  the  end-products,  the  answer 


METABOLISM  OF  PROTEINS  573 

is  easy.  The  amino-acids,  whatever  intermediate  stages  they  may 
pass  through,  whatever  cleavages,  oxidations,  or  reductions  they  may 
undergo,  yield  eventually  carbon  dioxide,  water,  and  comparatively 
simple  nitrogen-containing  substances,  which  after  further  changes 
appear  in  the  urine  principally  as  urea,  and  in  birds  and  reptiles  as 
uric  acid.  When  amino-acids  are  fed  to  mammals  or  introduced 
parenterally,  a  very  large  proportion  of  the  nitrogen  appears  in  the 
urine  as  urea.  The  same  is  true  when,  instead  of  simple  amino- 
acids,  polypeptides,  like  glycyl-glycin,  alanyl-alanin,  or  leucyl-leucin, 
are  given.  When  amino-acids  are  administered  to  birds,  the  great 
bulk  of  the  nitrogen  is  excreted  in  the  form  of  uric  acid.  Whether 
in  mammals,  and  if  so  to  what  extent,  uric  acid  is  also  one  of  the 
nitrogenous  end-products  of  the  decomposition  of  ordinary  proteins 
or  of  the  amino-acids  which  they  yield,  are  moot  questions.  In 
any  case,  the  most  important  and  characteristic  source  of  the  uric 
acid  in  mammals  and  the  other  groups  of  animals  whose  chief 
nitrogenous  end-product  is  urea,  is  not  the  ordinary  proteins,  but 
the  nucleins  which  form  constituents  of  the  nucleo-proteins. 

We  have  no  definite  information  as  to  the  production  of  water  from 
the  hydrogen  of  the  tissues,  except  what  can  be  theoretically  deduced 
from  the  statistics  of  nutrition  (p.  608).  A  few  words  will  be  said 
a  little  farther  on  about  the  production  of  carbon  dioxide  from 
proteins;  we  have  now  to  consider  the  seat  and  manner  of  formation 
of  the  nitrogenous  metabolites.  And  since  in  man  and  the  other 
mammals  urea  contains,  under  ordinary  conditions,  by  far  the 
greater  part  of  the  excreted  nitrogen,  it  will  be  well  to  take  it  first. 

Formation  of  Urea. — The  starting-point  of  all  inquiries  as  to  the 
place  of  formation  of  urea  is  the  fact  that  it  occurs  in  the  blood  in 
small  amount  (4  to  6  parts  per  10,000  in  man;  3  to  15  parts  per 
10,000  in  the  dog),  the  largest  quantity  being  found  when  the  food 
contains  most  protein  and  at  the  height  of  digestion,  the  smallest 
quantity  in  hunger  (Schondorff).  Evidently,  then,  some,  at  least, 
of  the  urea  excreted  in  the  urine  may  be  simply  separated  by  the 
kidney  from  the  blood;  and  analysis  shows  that  this  is  actually 
the  case,  for  the  blood  of  the  renal  vein  is  poorer  in  urea  than  that 
of  the  renal  artery,  containing  only  one-third  to  one-half  as  much. 
If  we  knew  the  exact  quantity  of  blood  passing  through  the  kidneys 
of  an  animal  in  twenty-four  hours,  and  the  average  difference  in 
the  percentage  of  urea  in  the  blood  coming  to  and  leaving  them, 
we  should  at  once  be  able  to  decide  whether  the  whole  of  the  urea  in 
the  urine  reaches  the  kidneys  ready  made,  or  whether  a  portion  of 
it  is  formed  by  the  renal  tissue.  Although  data  of  this  kind  are  as 
yet  inexact  and  incomplete,  it  is  not  difficult  to  see  that  all,  or  most 
of,  the  urea  may  be  simply  separated  by  the  kidney. 

If  we  take  the  weight  of  the  kidneys  of  a  dog  of  35  kilos  at  160  grammes 
(^^oth  of   the  body-weight  is  the  mean  result  of  a  great  number  of 


574  METABOLISM.  NUTRITION  AND  DIETETICS 

observations  in  man),  and  the  average  quantity  of  blood  in  them  at 
rather  less  than  one-fourth  of  their  weight,  or  35  grammes,  and  con- 
sider that  this  quantity  of  blood  passes  through  them  in  the  average 
time  required  to  complete  the  circulation  from  renal  artery  to  renal 
vein,  or,  say,  ten  seconds,  we  get  about  300  kilos  of  blood  as  the  flow 
through  the  kidneys  in  twenty-four  hours.  Even  at  0-3  per  1,000,  the 
urea  in  300  kilos  of  blood  would  amount  to  90  grammes.  Now,  Voit 
found  that  a  dog  of  35  kilos  body- weight,  on  the  minimum  protein  diet 
(450  to  500  grammes  of  lean  meat  per  day)  which  sufficed  to  maintain 
its  weight,  excreted  35  to  40  grammes  of  urea  in  the  twenty-four  hours. 
If,  then,  the  renal  epithelium  separated  somewhat  less  than  half  of  the 
90  grammes  urea  offered  to  it  in  the  circulating  blood,  the  whole  excre- 
tion in  the  urine  could  be  accounted  for,  and  the  blood  of  the  renal  vein 
would  still  contain  more  than  half  as  much  urea  as  that  of  the  renal 
arter^'.  So  that  the  whole  of  the  urea  in  the  urine  may  be  simply 
separated  by  the  kidney  from  the  ready-made  urea  of  the  blood. 

Another  line  of  evidence  leads  to  the  same  conclusion :  that  the 
kidney  is,  at  all  events,  not  an  important  seat  of  m-ea-formation. 
When  both  renal  arteries  are  tied,  or  both  kidneys  extirpated,  in  a 
dog,  urea  accumulates  in  the  blood  and  tissues;  and,  upon  the  whole, 
as  much  urea  is  formed  during  the  first  twenty-four  hours  of  the 
short  period  of  Ufe  which  remains  to  the  animal  as  would  under 
normal  circumstances  have  been  excreted  in  the  urine. 

Where,  then,  is  urea  chiefly  formed  ?  The  answer  to  this  question 
is  that,  while  some  urea  is  probably  produced  from  amino-acids  in 
.  aU  the  tissues,  one  organ  is  particularly  associated  wdth  this  function 
— namely,  the  liver. 

There  is  no  reason  to  suppose  that  the  hepatic  cells,  so  far  as  the 
repair  of  their  own  protoplasm  or  the  supply  of  energy  for  their  own 
special  work  is  concerned,  require  to  metabolize  particularly  large 
quantities  of  amino-acids  as  compared,  for  instance,  with  the 
muscles.  Glycin,  however,  they  must  have  for  the  manufacture  of 
glycochoUc,and  cystin  for  the  manufacture  of  thetaurin  of  taurocholic 
acid.  In  addition,  the  liver  is  known  to  possess  the  power  of  utilizing 
amino-acids  for  the  formation  of  dextrose  and  eventually  of  glyco- 
gen, and  a  portion  of  the  surplus  amino-acids  of  the  food  may  be 
withdrawn  from  the  blood  of  the  portal  vein  for  this  purpose,  just 
as  the  surplus  of  dextrose  is  withdrawn. 

The  liver  contains  a  relatively  large  amount  of  urea,  and  there  is 
strong  evidence  that  it  is  the  manufactory  in  which  a  great  part  of 
the  nitrogenous  relics  of  broken-down  proteins  reach  the  final  stage 
of  urea.     This  evidence  may  be  summed  up  as  follows: 

(i)  An  excised  '  surviving  '  liver  forms  urea  from  ammonium 
carbonate  mixed  with  the  blood  passed  througli  its  vessels,  while 
no  urea  is  formed  when  blood  containing  ammonium  carbonate  is 
sent  through  the  kidney  or  through  muscles.  Other  salts  of  am- 
monium, such  as  the  lactate,  the  formate,  and  the  carbamate,  under- 
go a  like  transformation  in  the  hver.  It  is  difficult,  in  the  light  of 
this  experiment,  to  resist  the  conclusion  that  the  increase  in  the 


METABOLISM  OF  PROTEINS  575 

excretion  of  urea  in  man,  when  salts  of  ammonia  are  taken  by  the 
mouth,  is  due  to  a  similar  action  of  the  hepatic  cells. 

(2)  If  blood  from  a  dog  killed  during  digestion  is  perfused  through 
an  excised  liver,  some  urea  is  formed,  which  cannot  be  simply 
washed  out  of  the  liver-cells,  because  when  the  blood  of  a  fasting 
animal  is  treated  in  the  same  way  there  is  no  apparent  formation 
of  urea  (v.  Schrocder).  This  suggests  that  during  digestion  certain 
substances  which  the  liver  is  capable  of  changing  into  urea  enter  the 
blood  in  such  amount  that  a  surplus  remains  for  a  time  unaltered. 
These  substances  may  come  directly  from  the  intestine;  or  they 
may  be  products  of  general  metabolism,  which  is  increased  while 
digestion  is  going  on;  or  they  may  arise  both  in  the  intestine  and  in 
the  tissues.  Leucin — which,  as  we  have  seen,  is  constantly,  or,  at 
least,  very  frequently,  present  in  the  intestine  during  digestion — 
can  certainly  be  changed  into  urea  in  the  body.  So  can  other 
amino-acids  of  the  fatty  series,  like  glycocoll  or  glycin,  and  aspartic 
acid,  and  it  has  been  shown  by  perfusion  experiments  that  this 
change  can  take  place  in  the  liver.  Further,  the  blood  of  the  portal 
vein  during  digestion  contains  several  times  as  much  ammonia  as 
the  arterial  blood,  and  the  excess  disappears  in  the  liver. 

(3)  Uric  acid — which  in  birds  is  the  chief  end-product  of  protein 
metabolism,  as  urea  is  in  mammals — is  formed  in  the  goose  largely, 
and  almost  exclusively,  in  the  liver.  This  has  been  most  clearly 
shown  by  the  experiments  of  Minkowski,  who  took  advantage  of 
the  communication  between  the  portal  and  renal-portal  veins 
(p.  379)  to  extirpate  the  liver  in  geese.  When  the  portal  is  ligated 
the  blood  from  the  alimentary  canal  can  still  pass  by  the  round- 
about road  of  the  kidney  to  the  inferior  cava,  and  the  animals 
survive  for  six  to  twenty  hours.  While  in  the  normal  goose  50  to 
60  per  cent,  of  the  total  nitrogen  is  eliminated  as  uric  acid  in  the 
urine,  and  only  9  to  18  per  cent,  as  ammonia,  in  the  operated  goose 
uric  acid  represents  only  3  to  6  per  cent,  of  the  total  nitrogen,  and 
ammonia  50  to  60  per  cent.  A  quantity  of  lactic  acid  equivalent 
to  the  ammonia  appears  in  the  urine  of  the  operated  animal,  none 
at  all  in  the  urine  of  the  normal  bird.  The  small  amount  of  urea  in 
the  normal  urine  of  the  goose  is  not  affected  by  extirpation  of  the 
liver.  And  while  urea,  when  injected  into  the  blood,  is  in  the 
normal  goose  excreted  as  uric  acid,  it  is  in  the  animal  that  has  lost 
its  liver  eliminated  in  the  urine  unchanged. 

(4)  After  removal  of  the  liver  in  frogs,  or  in  dogs  which  have 
survived  the  previous  connection  of  the  portal  vein  with  the  inferior 
vena  cava  by  an  Eck's  fistula  (p.  379),  the  quantity  of  urea  excreted 
is  markedly  diminished,  and  the  ammonium  salts  in  the  urine  are 
increased.  When  the  Eck's  fistula  is  established  and  the  portal 
vein  tied,  without  any  further  interference  with  the  hepatic  circula- 
tion, the  amount  of  urea  in  the  urine  is  not  lessened  to  nearly  the 


576  METABOirsM.  NUTRITION  AND  DIETETICS 

same  extent,  evidently  because  the  substances  from  which  urea  is 
formed  still,  for  the  most  part,  gain  access  to  the  liver  through  the 
hepatic  artery  and  by  means  of  the  back-flow  which  is  known  to 
take  place  through  the  hepatic  vein.  Yet  while  in  normal  dogs  the 
proportion  of  ammonia  to  urea  in  the  urine  is  only  1:22  to  i :  73, 
in  dogs  with  Eck's  fistula  it  rises  to  1:8  to  1:33.  If  the  animals 
are  kept  on  a  diet  poor  in  proteins,  no  symptoms  may  develop  for 
i  con^derable  time.  But  if  much  protein  is  given,  characteristic 
symptoms,  including  convulsions,  always  appear.  These  may  be 
produced  by  the  saturation  of  the  organism  with  ammonia  com- 
pounds, which  are  formed  from  the  proteins  as  in  the  normal  animal, 
but  which  the  liver,  with  its  circulation  crippled,  is  unable  to  cope 
with,  and  to  completely  change  into  urea,  although  the  statement 
has  been  made  that  when  ammonia  or  ammonium  salts  are  injected 
into  the  blood  larger  quantities  must  be  present  to  produce  these 
symptoms  than  are  found  in  animals  with  the  Eck's  fistula. 
Although  the  portal  vein  carries  to  the  liver  a  much  greater  supply 
of  blood  than  the  hepatic  artery,  ligation  of  the  latter  causes  a  greater 
diminution  in  the  ratio  of  the  amount  of  urea  to  the  total  nitrogen 
in  the  urine  than  ligation  of  the  former.  This  indicates  that  a  good 
supply  of  oxygen  is  an  important  factor  in  the  formation  of  urea  in 
the  liver  (Doyon  and  Dufourl).  But  this  is  no  proof  that  the  process 
by  which  it  is  formed  is  an  oxidation.  The  work  of  the  liver,  like 
that  of  other  tissues,  is  no  doubt  deranged  by  lack  of  oxygen. 

(5)  In  acute  yellow  atrophy,  and  in  extensive  fatty  degeneration 
of  the  liver,  urea  may  almost  disappear  from  the  urine,  and  leucin, 
tyrosin,  and  other  amino-acids  may  appear  in  it  along  with  a  much 
larger  amount  of  ammonia  than  normal.  Here  it  may  be  supposed 
that  the  amino-acids  and  ammonia  formed  in  the  intestine  in 
the  digestion  and  absorption  of  proteins,  perhaps  also  amino- 
groups  formed  in  the  tissues  which  would  normally  be  culled 
from  the  blood  by  the  hepatic  cells  for  the  manufacture  of  urea, 
pass  unchanged  through  the  degenerated  liver,  and  are  excreted  by 
the  kidney. 

It  would,  however,  be  very  easy  to  overdo  this  argument;  for  it 
is  sometimes  observed  that  in  pathological  and  experimental  condi- 
tions in  which  the  liver  has  suffered  severely  considerable  quantities 
of  urea  continue  to  be  excreted.  Urea  does  not  entirely  cease  to 
be  produced  even  when  the  liver  is  removed;  and  it  must  again 
be  pointed  out  that  there  is  reason  to  believe  that  the  formation 
of  urea  is  not  a  function  peculiar  to  the  liver,  but  one  shared  prob- 
ably with  all  tissues.  The  liver  certainly  does  not  arrest  the  whole 
of  the  amino-acids  coming  from  the  alimentary  canal;  for  the  non- 
protein nitrogen  in  the  muscles  is  distinctly  increased  during  the 
absorption  of  amino-acids,  and  the  muscular  tissue,  even  when  freed 
from  blood,  contains  some  urea,  which  in  all  probability  is  formed 


METABOLISM  OF  PROTEINS  577 

there  in  the  decomposition  of  amino-acids.  Some  writers,  indeed, 
take  the  view  that  the  muscles,  containing  as  they  do  three-fourths 
of  the  proteins  of  the  body,  and  utihzing  as  they  appear  to  do  a 
large  proportion  of  the  amino-acids  of  the  food-protein,  are  more 
important  seats  of  urea  formation  than  the  liver.  Yet  the  fact  that 
it  is  far  easier  to  demonstrate  this  power — e.g.,  by  perfusion  experi- 
ments— for  the  liver  than  for  such  tissues  as  the  muscles,  renders  it 
difficult  to  avoid  the  conclusion  that  in  the  preparation  of  an  end- 
product  so  important  as  that  in  which  the  great  bulk  of  the  nitrogen 
leaves  the  body,  a  certain  degree  of  specialization  has  been  developed, 
and  that  this  preparation  has  been  largely  entrusted  to  a  special 
organ.  And,  while  it  may  be  true  that  larger  amounts  of  amino-acids 
are  taken  up  and  utilized  by  the  muscles  than  by  the  liver  under 
certain  conditions,  this  does  not  show  that  amino-groups  removed 
from  the  amino-acids  in  the  muscles  may  not  be  largely  transferred 
to  the  liver  before  being  changed  into  urea.  Further,  the  transforma- 
tion of  amino-acids  into  dextrose  (and  glycogen)  may  be  assumed  to 
entail  a  considerable  absorption  of  amino-acids  by  the  hepatic  cells. 

Processes  by  which  Urea  is  formed. — In  the  case  of  only  one  of  the 
amino-acids  derived  from  proteins  can  urea  be  obtained  by  a  simple 
process  of  hydrolytic  cleavage.  This  is  arginin  (a-amiiio-S-guanidin- 
M-valerianic  acid) — that  is  to  say,  normal  valerianic  acid, 

CH3.CH2.CH2.CH2.COOH, 

S  y         ii         a 

in  which  an  amino  group  is  attached  to  the  a  carbon  atom,  while 
giianidin  ^jj^^C.NH  is  attached  to  the  d  carbon  atom  (p.  557). 

When  arginin  is  hydro lysed  by  barium  hydroxide  it  yields  urea  and 
ornithin  (diamino-valcrianic  acid),  half  of  the  nitrogen  of  the  arginin 
appearing  in  each.     Thus, 

NH2 

^^^Xc.NH  .CH2.CH2.CH2.CH  .COOH  -I-  H2O  = 

Arginin. 

NHa 
^HaXc  =0+  NH2.CH2.CH2.CH2.CH.COOH 

Urea.  Ornithin. 

The  amount  of  arginin,  and  therefore  the  amount  of  urea  which  can  be 
artificially  obtained  in  this  way,  varies  extremely  with  the  different 
proteins.  Thus,  salmin,  a  protamin  (p.  2),  prepared  from  the  milt 
of  salmon,  yields  84'3  per  cent,  of  its  weight  of  arginin,  while  the 
casein  of  cow's  milk  yields  only  4-8  per  cent.,  and  gluten-fibrin,  one  of 
the  proteins  of  wheat,  only  3  per  cent.  In  the  body  the  hydrolysis  of 
arginin  to  urea  and  ornithin  is  accomplished  by  the  ferment  arginase 
(Kossel  and  Dakin).  This  ferment  is  found  in  the  liver,  and  also  in 
many  other  organs.  The  urea  formed  in  tliis  way  appears  very 
rapidly  in  the  urine.  The  ornithin  itself  is  then  more  slowly  transformed 
into  urea.     Since  the  ordinary  food-proteins  arc   poor  hi  arginin,  the 

37 


578  '     METABOLISM,  NUTRITION  AND  DIETETICS 

amount  of  urea  which  can  possibly  be  formed  in  mammalian  metabolism 
by  this  process  cannot  be  large,  even  if  most  of  the  arginin,  as  is  the 
case  when  it  is  fed  to  an  animal,  is  transformed  into  urea. 

There  is  no  reason  to  suppose  that  urea  can  be  directly  split  off  from 
the  other  amino-acids  with  which  we  are  concerned.  A  comparison 
of  their  constitutional  formulae  with  that  of  urea  (or  with  that  of  uric 
acid)  shows  that  a  more  far-reaching  decomposition  must  take  place 
before  products  are  obtained  from  which  urea  (or  uric  acid)  can  be 
formed.  Urea  has  been  artificially  obtained  from  protein  by  oxidation 
with  an  ammoniacal  solution  of  permanganate  at  body-temperature. 
When  the  protein  is  first  split  into  its  cleavage  products,  and  these  are 
then  oxidized,  a  very  large  amount  of  urea  is  produced — e.g.,  as  much 
as  3  grammes  of  urea  from  lo  grammes  of  glycin. 

While  these  facts  suggest  possible  ways  of  formation  of  urea  in  the 
body,  we  cannot  assume  that  what  happens  in  the  test-tube  must 
happen  in  the  tissues.  The  best  evidence  is  to  the  effect  that  in  the 
body  the  removal  of  the  amino-group  (NH2)  in  the  form  of  ammonia 
from  the  amino-acids  is  the  essential  step  in  the  formation  of  at  least 
a  great  part  of  the  urea,  which  is  then  sjmthcsized  from  ammonia  and 
carbonic  acid.  The  possibility  exists  that  this  deamination  (or  deamidi- 
zation)  of  the  amino-bodies  is  the  result  of  hydrolysis,  or  of  oxidation, 
or  of  reduction,  or  of  a  combination  of  these  processes.  In  any  case  it 
is  to  such  ammonium  compounds  as  have  been  already  mentioned  as 
being  transformed  into  urea  when  circulated  through  an  excised  liver 
(p.  574)  that  we  have  to  look  for  the  source  of  a  portion,  and  probably 
a  large  portion,  of  the  urea.  Ammonia  in  the  form  of  carbonate  or 
carbamate  is  constantly  found  in  the  blood  (p.  575).  The  excess  of 
ammonia  in  the  portal  blood,  which,  however,  is  not  admitted  by  all 
observers  to  be  very  large  or  very  constant,  has  been  interpreted  as 
indicating  that  a  considerable  decomposition  of  amino-acids  with  libera- 
tion of  the  amino-groups  occurs  in  the  intestinal  lumen  or  the  intestinal 
wall.  It  is  not  established  beyond  doubt  that  ammonia  is  itself  present 
in  the  protein  molecule,  or  that  its  liberation  in  the  hydrolysis  of 
proteins  can  take  place  except  at  the  expense  of  further  decomposition 
of  amino-bodies.  It  has  been  shown,  however,  that  a  great  part  of 
the  ammonia  in  the  blood  is  produced  in  the  decomposition  of  protein 
in  the  digestive  tube  by  putrefactive  bacteria  (Folin  and  Denis).  This 
is  a  necessary  part  of  the  reaction  by  which  phenol  and  indol  are 
formed  in  the  intestine. 

It  has  been  generally  taught  that  the  deamidization  of  the  surplus  of 
amino-bodies  takes  place  chiefly  in  the  liver,  the  extra  nitrogen  being 
thus  '  shunted  '  out  of  the  blood-stream  before  it  has  had  a  chance  to 
reach  the  tissues.  It  would  seem  more  advantageous  in  the  light  of 
our  present  knowledge  that  a  large  and,  so  to  say,  a  miscellaneous 
assortment  of  amino-bodies  should  be  placed  at  the  disposal  of  the 
tissues  to  facilitate  the  selection  of  those  which  are  indispensable. 
We  have  seen  that  tissues  such  as  muscle  can  and  do  take  up  amino- 
acids  when  protein  is  digested  in  the  intestine,  and  it  is  very  probable 
that  they  take  up  not  merely  the  relatively  small  amount  necessary  to 
replace  their  wear  and  tear,  but  also  a  portion  of  the  surplus,  which 
after  deamidization  in  the  cells  takes  its  place  as  a  source  of  energy 
to  drive  the  machine.  The  nitrogen  in  the  form  of  ammonia  may  pass 
back  into  the  blood,  and  may  thus  be  carried  to  the  liver  for  conversion 
into  urea.  It  is  not  necessary,  however,  to  suppose  that  all  of  the 
nitrogen  must  perforce  make  this  journey  before  being  changed  into 
urea.  There  is  evidence  that  all  the  tissues  share  to  some  extent  with 
the  liver  the  power  of  forming  urea  just  as  they  share  with  the  li\'er  the 


METABOLISM  OF  PROTEINS  579 

power  of  splitting  off  NHg  from  the  amino-bodies.  It  may  be  that 
the  liver  surpasses  other  tissues  in  its  deamicli-'cing  power  just  as  it  seems 
to  surpass  other  tissm  s  in  its  power  of  transforming  ammonium  com- 
pounds into  urea.  But  this  does  not  prevent  at  least  a  considerable 
proportion  of  the  amino-substances  absorbed  from  the  intestine  from 
passing  into  the  general  circulation.  It  is  of  importance  to  remark 
that  such  hydrolytic  cleavages  as  are  associated  with  the  splitting  of 
protein  into  amino-acids,  etc.,  only  slightly  reduce  the  available  energy' 
of  the  compounds.  If,  as  is  most  probable,  the  liberation  of  the  nitrogen 
from  the  amino-acids  is  also  accomplished  by  hydrolytic  cleavage  (sup- 
posedly by  a  ferment  dcsaminase),  the  residue,  relatively  rich  in  carbon, 
will  still  be  available  for  yielding  to  the  body  by  its  oxidation  an  amount 
of  encrg)'  not  much  less  than  could  be  obtained  from  the  original 
protein. 

The  combination  of  ammonia  with  carbon  dioxide  and  the  conversion 
of  the  carboniite  into  urea,  perhaps  through  the  intermediate  stage  of 
ammonium  carbamate,  does  not  require  any  oxidation.     Thus, 

/OH  /O.NH4  /O.NH4  /NH. 

C^O    +2NH3-C=0  ;    -HgO-CfO  ;    -HgO^C^O 

\OH  \O.NH.  NNHa  NNH, 


Carbonic  acid.  Ammonium  Ammonium  Urea. 

carbonate.  carbamate. 

Another  way  in  which  some  of  the  urea  may  be  produced  is  by  the 
direct  formation  of  ammonium  carbamate  in  the  katabolism  of  amino- 
acids  without  the  preliminary  liberation  of  ammonia.  By  the  loss  of  a 
molecule  of  water  the  carbamate  would  then  become  urea.  But  if,  as 
there  is  every  reason  to  believe,  a  part  of  the  carbonaceous  residue  is 
converted  into  carbo-hydrate,  a  certain  amount  of  oxidation  must 
occur  in  the  transformation. 

Such  compounds  as  guanin,  sarkin  or  hypoxanthin,  xanthin,  uric 
acid,  and  krcatin,  used  to  be  cited  as  among  the  possible  intermediate 
substances  between  protein  and  urea.  But  while  there  is  now  complete 
evidence  that  the  first  three  bodies  can  be  and  are  converted  into  uric 
acid,  there  is  nothing  at  all  to  indicate  that  they  are  stages  on  the 
way  to  urea.  Uric  acid  is,  indeed,  very  closely  related  to  urea,  and 
can  be  made  to  yield  it  by  oxidation  outsiele  the  body.  Not  only  so, 
but  it  is,  in  part  at  least,  excreted  as  urea  when  given  to  a  mammal 
by  the  mouth  and  it  replaces  urea  as  the  great  enel-product  of  nitro- 
genous metabolism  almost  wholly  in  the  urine  of  birds  and  reptiles. 
But  none  of  these  things  can  be  admitted  as  evidence  that  in  the 
normal  metabolism  of  mammals  uric  acid  lies  on  the  direct  line  from 
protein  to  urea.  Kreatin  exists  in  the  body  in  greater  amount  than 
any  of  these,  muscle  containing  from  0-2  to  0-4  per  cent,  of  it;  and  the 
total  quantity  of  nitrogen  present  at  an  3^  given  time  as  kreatin  is  not 
only  greater  than  that  of  the  nitrogen  present  in  urea,  but  greater 
than  the  whole  excretion  of  nitrogen  in  twenty-four  hours.  But 
although  there  are  facts  which  indicate  that  kreatin  is  an  important 
derivative  of  the  decomposed  tissue  proteins  (p.  586)  there  is  no 
evidence  that  it  is  related  to  urea  formation. 

Formation  of  Uric  Acid. — Uric  acid,  like  urt^a,  is  separated  from 
the  blood  by  the  kidneys,  not  to  any  appreciable  e.xtent  formed  in 
them.  In  birds,  and  often  in  man,  it  can  be  detected  in  normal 
blood.  It  is  present  in  increased  amount  in  the  blood  and  transuda- 
tions of  gouty  patients,  in  whose  joints  and  ear-cartila§'es  it  often 


58o  METABOLISM,  NUTRITION  AND  DIETETICS 

forms  concretions.     '  Chalk-stones  '  may  contain  mure  than   hali 
their  weight  of  sodium  urate. 

As  to  the  place  and  manner  of  formation  of  uric  acid>  it  has  already 
been  stated  that  in  birds,  after  extirpation  of  the  liver,  the  uric  acid 
excretion  is  greatly  diminished,  and  that  ammonium  lactate  appears 
instead  in  the  urine.  The  simplest  interpretation  of  this  result  is, 
that  ammonia  and  lactic  acid  pass  into  the  urine  because  they  can 
no  longer  be  utilized  for  the  synthesis  of  uric  acid.  Chemical 
schemata  can  indeed  be  constructed,  which  show  more  or  less 
plausibly  how  lactic  acid,  pyuvic  acid  (p.  537),  and  other  substances 
reacting  with  ammonia  or  with  the  urea  derived  from  it  (and  birds 
form  some  urea)  might  yield  uric  acid.  It  has  been  further  stated 
that  when  blood  containing  ammonium  lactate  is  circulated  through 
the  surviving  liver  of  the  goose,  an  increase  in  the  uric  acid  content 
of  the  blood  occurs.  As  demonstrated  by  control  experiments,  this 
inciease  is  too  great  to  be  due  merely  to  the  sweeping  out  of  pre- 
viously formed  uric  acid  from  the  hepatic  cells;  also  the  feeding  of 
lactic  acid,  pyuvic  acid,  and  other  organic  acids  leads  to  an  increased 
output  of  uric  acid.  The  story  seems  fairly  complete,  although 
criticisms  have  not  been  lacking.  It  has  been  suggested,  for  instance, 
that  for  some  reason  the  loss  of  the  liver  leads  to  acidosis,  an  in- 
creased production  of  acids,  especially  lactic  acid,  in  the  organism; 
that  ammonia,  which  would  otherwise  be  employed  in  the  formation 
of  uric  acid,  is  needed  to  neutralize  these  acids,  and  that  the  appear- 
ance of  this  ammonia  in  the  urine  is  only  a  secondary  consequence 
of  the  elimination  of  the  liver.  The  deficiency  in  the  uric  acid 
excreted,  it  is  said,  is  therefore  due,  not  to  inability  on  the  part  of 
the  remaining  tissues  to  form  uric  acid,  but  to  the  absence  of  the 
Ammonia  which  they  require  for  its  formation.  This  criticism,  if 
it  were  admitted  as  against  the  current  interpretation  of  such  ob- 
servations on  the  bird's  liver,  could  scarcely  be  denied  some  validity 
as  against  the  current  interpretation  of  similar  observations  on  the 
results  of  interference  with  the  mammahan  hver.  It  is  therefore 
important  to  point  out  that  there  is  still  the  same  deficiency  of  uric 
acid  when  alkali  is  administered  to  neutralize  the  acids,  although 
ammonia  ought  now  to  be  available.  There  can  be  no  question, 
then,  that  the  liver  in  birds  is  the  seat  of  an  extensive  synthesis  of 
uric  acid,  and  there  is  little  doubt  that  ammonia  compounds  are 
essentially  concerned  in  the  process,  whatever  the  role  of  the  lactic 
or  other  acids  may  be.  A  similar  synthetic  formation  of  uric  acid 
from  ammonia  and  a  derivative  of  lactic  acid  may  take  place  in 
mammals,  and  probably  exclusively  in  the  liver,  but  it  is  of  much 
less  importance.  Another  way  in  which  uric  acid  arises  both  in 
mammals  and  in  birds  is  by  the  spHtting  and  oxidation  of  nucleins 
This  is  by  far  the  most  important  mode  of  formation  in  mammals, 
as  synthesis  is  the  chief  mode  of  formation  in  birds.     In  both  groups 


METABOLISM  OF  PROTEINS  581 

of  animals  the  oxidative  production  of  uric  acid  takes  place,  not  in 
any  "particular  organ,  but  in  the  tissues  in  general,  including  the  liver. 
It  has  been  shown  that  when  air  is  blown  through  a  mixture  of 
splenic  pulp  and  blood,  uric  acid  is  formed  from  purin  bodies  already 
present  in  the  spleen.  When  the  quantity  of  these  is  increased  by 
the  decomposition  of  nucleins  induced  by  slight  putrefaction,  the 
yield  of  uric  acid  is  also  increased.  Uric  acid  is  also  formed  by  the 
perfectly  fresh  surviving  spleen,  liver,  and  thymus  in  the  presence 
of  oxygen,  and  the  quantity  is  increased  when  purin  bodies  are 
artificially  added. 

Sources  of  the  Uric  Acid. — It  is  well  established  that  in  the  bird 
it  arises  both  from  amino-acids  derived  from  the  hydrolysis  of 
protein  and  from  nuclein  compounds  and  their  derivatives  in  the 
food  and  tissues.  The  aniino-acids  constitute  by  far  the  greatest 
source  of  uric  acid  in  these  animals  and  in  the  reptiles,  and  it  is 
practically  certain  that  the  course  of  the  decomposition  of  the 
amino-acids  and  the  form  in  which  nitrogen  is  liberated  from  them 
in  its  transformation  into  this  end-product  are  not  essentially  differ- 
ent from  what  obtains  in  the  formation  of  urea  in  the  mammal  and 
the  amphibian.  This  is  sufficiently  illustrated  by  the  role  played  by 
ammonia  and  ammonia  compounds  in  the  production  of  uric  acid 
in  the  birds  and  their  congeners.  In  the  mammal,  the  taking  of 
food  rich  in  nucleated  cells,  and  therefore  in  nucleo-proteins  and 
nucleins,  the  characteristic  conjugated  proteins  of  nuclei  (thymus 
gland,  pig's  pancreas,  and  herring  roe),  or  of  food  rich  in  purin 
bases  (Liebig's  meat  extract),  increases  the  quantity  of  uric  acid  in 
the  urine.  The  increase  is  mainly  due  to  the  production  of  uric 
acid  from  the  nuclein  substances  of  the  food.  But  this  is  not  the 
only  source  of  the  uric  acid,  since  extracts  of  the  thymus  gland 
containing  only  traces  of  nucleins  or  nucleic  acid  cause,  when  in- 
jected, a  characteristic  increase  in  the  uric  acid  excretion,  just  as 
the  entire  gland  does  when  taken  by  the  mouth.  And  during  the 
period  of  increased  nitrogen  excretion  occasioned  by  a  meal  contain- 
ing protein,  the  increase  in  the  uric  acid  occurs  particularly  in  the 
hours  immediately  foMowng  the  ingestion  of  the  food,  and  does  not 
last  so  long  as  the  increase  in  the  urea.  Now,  the  nucleins  of  the 
food  are  comparatively  little  affected  during  the  earlier  stages  of 
digestion  (Hopkins  and  Hope).  Whether  in  mammals  any  portion 
of  the  uric  acid  comes  from  amino-acids  is  still  in  doubt,  but  there 
are  facts  which  indicate  that  a  fraction  of  it  may  do  so.  We  may 
conclude,  therefore,  that  in  the  mammal,  as  well  as  in  the  bird,  a 
portion  of  the  uric  acid,  although  certainly  a  far  smaller  portion  in 
the  mammal,  is  derived  from  bodies  other  than  the  nuclein  substances 
of  the  food — that  is  lo  say,  from  the  nuclein  substances  of  the  tissues 
contained  particularly  in  the  cell-nuclei  and  probably  from  the 
ordinary  proteins  of  both  food  and  tissues.     The  portion  derived 


582  METABOLISM.  NUTRITION  AND  DIETETICS 

from  the  proteins  may  be  assumed  to  be  that  small  fraction  which 
has  already  been  spoken  of  as  synthetically  formed. 

Metabolism  of  the  Nucleic  Acids  and  Purin  Bases. — ^Our  loiow- 
ledge  of  the  metabolism  of  the  nucleo-proteins  and  nucleins  has 
been  greatly  augmented  in  recent  years.  When  nucleo-protein  is 
digested  by  gastric  juice,  a  certain  amount  of  protein  is  easily  split 
off  and  hydrolysed  to  peptone  and  the  other  ordinary  products 
of  proteolysis.  An  insoluble  residue  of  nuclein  remains.  This  is 
acted  upon  with  difficulty  by  gastric  juice,  although  eventually  an 
active  juice  will  split  it  up  also.  By  the  action  of  pancreatic  juice, 
or  by  heating  with  dilute  acids,  it  is  more  easily  hydrolysed,  yielding 
a  further  quantity  of  protein  along  with  nucleic  acid.  This  second 
fraction  of  protein,  which  is  split  off  with  so  much  more  difficulty 
than  the  first,  undergoes  proteolysis  in  the  usual  way.  The  result- 
ing amino-acids  no  doubt  take  their  place  in  the  general  metabolism 
precisely  like  the  amino-acids  derived  from  ordinary  proteins,  and 
yield  the  same  end-products.  As  regards  the  nucleic  acid  (or  rather 
acids,  since  different  nucleo-proteins  contain  different  nucleic  acids), 
pancreatic  juice  is  practically  inert,  although  succus  entericus  can 
effect  a  partial  hydrolysis.  For  their  complete  decomposition  more 
drastic  treatment  is  required — namely,  heating  with  hydrochloric 
acid  in  a  sealed  tube.  Thus  treated,  nucleic  acids  yield  a  number 
of  components,  out  of  which  they  may  be  assumed  to  be  built  up, 
as  the  proteins  are  built  up  out  of  amino-acids,  etc.  The  charac- 
teristic components  are  purin  bases  (adenin,  C5H3N4.NH2;  guanin, 
C5H3N4O.NH2;  hypoxanthin,  C5H4N4O;  and  xanthin,  C5H4N4O2) ; 
pyrimidin  bases  (uracil,  C4H4N2O2;  cytosin,  C4H3N2O.NH2;  thymin, 
C4H3N2O2.CH3);  phosphoric  acid  and  a  carbo-hydrate  group. 

Some  of  the  nucleic  acids  contain  all  these  components;  they  are 
sometimes  spoken  of  as  the  true  nucleic  acids.  In  others  certain  of  the 
components  are  absent,  and  to  these  nucleic  acids  the  name  nucleotids 
has  been  applied.  The  purin  bases  are  always  present.  The  carbo- 
hydrate group  varies  in  different  nucleic  acids,  being  in  some  a  hexose 
(p.  529),  in  others  a  pentose  (p.  482).  The  pentose  (Z-ribose  is  especially 
often  met  with.  It  is  probable  that  the  nucleotids  are  merely  simpler 
decomposition  products  of  the  true  nucleic  acids.  Thus,  inosinic  acid, 
a  nucleotid  first  isolated  from  meat  extract,  yields  phosphoric  acid, 
cZ-ribose,  and  the  purin  base  hypoxanthin.  The  nucleotid  guanylic  acid 
found  in  the  pancreas  yields  phosphoric  acid,  rf-ribose,  and  the  purin 
base  guanin.  There  is  evidence  that  nucleic  acids  may  be  built  up  out 
of  a  number  of  nucleotid  groups,  and  for  this  reason  they  have  been 
termed  poljTiucleotids  (Levene);  The  purin  bases  have  a  very  close 
chemical  relationship  to  uric  acid,  which,  like  them,  is  characterized  by 
the  possession  of  a  group  called  the  purin  nucleus.  For  convenience 
of  reference  the  atoms  composing  tlie  purin  nucleus  are  numbered, 
and  the  purin  bodies  are  named  with  reference  to  the  position  of  the 
carbon  atom  or  atoms  at  which  oxygen  or  the  amino -group  (NH2)  is 
introduced.  Purin  consists  of  the  nucleus  with  H  atoms  introduced  at 
the  pomts  shown  in  the  constitutional  formula.  Adenin  is  a  6-'  mino- 
purin — i.e.,  purin  in  which  NH2  replaces  the  H  attached  to  C(e).     Guanin 


METABOLISM  OF  PROTEINS  583 

is  2-amino-6-oxypurin,  NHg  being  united  with  C(2)  and  oxygen  with  C(o) 
in  purin.  Uric  acid  is  2,  6,  8-trioxypurin — i.e.,  purin  in  which  oxygen 
is  united  to  the  carbon  atoms  2,  6,  and  8.  Hypoxanthin  is  6-oxypurin, 
oxygen  being  introduced  at  the  position  of  C(6)  in  purin.  By  removal 
of  the  amino-group  from  adenin  hypoxanthin  is  formed.  Xanthin  is 
2,  6,  dioxypurin,  oxygen  being  introduced  at  C(2)  and  C(6)  in  the  purin 
molecule.  Xanthin  can  be  derived  from  guanin  in  tlie  same  way  as 
hypox:,nthin  from  adenin. 

N,!)— C(6)  N=CH  N=C.NH, 

II  II  II 

C(2)     C(5)— Nff)  HC     C— NH  HC     C— NH 

I  I   /^<«'     I  I  ^^^      I!  '^  y^^ 

N(3)    C,4,— N,o)  N— C— N  N— C— K 

Purin  nucleus.  Purin.  Adenin. 

NH— CO  NH— CO  N=C.OH  NH— CO 

II  i  I  II  J  I 

NHg.C        C— NH        CO     C— NH       HC     C— NH        CO     C— NH 

II         II       >«    I  II      >0       II       I       >H     I         II       >CH 

N  — C— N  NH— C— NH  N— C— N  NH— C— N 

Guanin.  Uric  acid.  Hypoxanthin.  Xanthin. 

Besides  the  purin  bases  combined  in  the  nuclein  substances,  purin  bases  * 
and  uric  acid  are  widely  spread  in  the  tissues  in  the  free  state,  although 
in  very  small  amounts. 

A  portion  of  the  intake  of  purin  bodies  is  therefore  ready  formed, 
especially  in  the  animal  constituents  of  the  food,  and  docs  not  require 
the  decomposition  of  nucleic  acid  for  its  liberation.  The  nuclei  of 
vegetable  cells  contain  nucleo-proteins,  and  accordingly  can  contribute 
to  the  purin  intake.  The  most  interesting  contribution  of  vegetable 
origin  has  been  previously  alluded  to  (p.  475) — namely,  the  methyl 
purins  forming  the  active  principles  of  tea,  coffee,  and  cocoa,  caffein, 
or  I,  3,  7-trimethylxanthin  (C8H10N4O2),  theobromin,  or  3,  7-dimethyl- 
xanthin  (CjHgN^Og),  and  theophyllin,  or  i,  3  -  dimethylxantliin 
(CeHsNPa). 

CHo.N— CO  NH— CO  CHo.N— CO 

II  II  I       I 

■O  C— N.CH3  CO      C— N.CH3  CO  C— NH 

CH  I  I        ^CH  I  Vh 


I       I        /-""  I  \.^^^''  I  / 

CH3.N— C— N  CH3.N  —  C-^  CH3.N— C— N 

Caffein.  Theobromin.  Theophyllin. 

Nucleic  acid,  as  stated,  can  be  partially  decomposed  by  the 
succiis  entericus,  by  means  of  a  ferment  called  nuclease  or,  more 
accurately,  nucleic-acidase.  The  groups  into  which  it  is  split 
are  nucleotids  (see  above).  By  another  ferment,  nucleotidase,  a 
portion,  at  any  rate,  of  the  nucleotids  is  further  decomposed  to 
yield  nucleosides,  bodies  of  the  glucoside  class  containing  a  com- 
pound of  a  piuin  base  with  the  carbo-hydrate  group  of  the  nucleic 
acid,  to  which  phosphoric  acid  is  also  coupled.  Beyond  this  stage 
the  hydrolysis  of  nucleic  acid  does  not  proceed  in  the  intestine. 


5^4  METABOLISM,  NUTRITION  AND  DIETETIC^ 

The  resultant  products,  probably  along  with  unchanged  nucleic 
acid,  are  a'bsorbed,  mainly  at  least,  by  way  of  the  bloodvessels. 

It  will  be  well,  however,  to  remember  that  our  knowledge  of 
the  digestion  of  the  nuclein  bodies  is  still  incomplete,  and  the 
natural  tendency  of  the  mind  to  think  in  diagrams  is  apt  to  give  it 
greater  precision  than  is  justified  by  the  facts;  for  example,  it  is 
known  that  even  gastric  juice  is  capable  of  liberating  some  of  the 
phosphoric  acid  from  nucleo-proteins. 

In  the  tissues  the  absorbed  products  of  the  digestion  of  nucleic 
acids  may  be  partially  utilized  without  further  decomposition  for 
the  synthesis  of  nucleo-proteins,  to  take  the  place  of  those  which  are 
destroyed  in  the  metabolism  of  the  cells;  or  they  may  be  split  com- 
pletely into  their  components,  and  these  resynthesized.  Finally, 
and  this  fate  is  probably  not  long  delayed  in  the  case  of  the  surplus 
of  purin  compounds  contained  in  ordinary  dietaries,  both  the  purins 
of  the  food  and  the  purins  arising  from  the  waste  of  the  tissues  are 
for  the  most  part  converted  into  uric  acid  and  excreted  in  the  urine. 
Small  quantities  of  purins  leave  the  body  in  the  faeces  (p.  419). 
The  phosphoric  acid  can  be  utilized  not  only  for  the  building  of 
nucleo-proteins,  but  for  the  synthesis  of  phosphatides.  Eventually 
it  is  eliminated  as  phosphates  in  the  urine.  The  carbo-hydrate 
groups,  so  far  as  they  are  not  utilized  in  the  synthesis  of  nucleic 
acids,  may  be  supposed  to  undergo  metabolism  like  other  carbo- 
hydrates. The  metabolic  history  of  the  pyrimidin  bases  has  not 
been  made  clear. 

Steps  in  Formation  of  Uric  Acid. — As  to  the  manner  in  which 
uric  acid  arises  from  the  nuclein  substances,  we  may  picture  the 
process  as  taking  place  by  the  following  steps  :  Certain  organs  have 
been  shown  to  contain  ferments  which  split  up  nucleo-proteins  into 
protein  and  nucleic  acid.  This  nucleic  acid,  or  nucleic  acid  arising 
in  other  ways  in  the  metabolism  of  nuclein,  and  also  any  nucleic 
acid  absorbed  as  such  from  the  alimentary  canal  in  the  digestion  of 
nuclein-containing  substances,  are  then  decomposed  by  another 
ferment,  similar  to  or  identical  with  the  nuclease  or  nucleic-acidase 
previously  encountered  in  the  intestine.  The  resulting  nucleotids  are 
split  up  by  a  special  ferment  (nucleotidase)  so  as  to  yield  nucleosides. 
These  are  in  turn  decomposed  by  appropriate  enzymes  (nucleo- 
sidases), so  that  we  finally  arrive  at  the  individual '  building-stones,' 
the  nucleic  acid  molecule,  phosphoric  acid,  the  carbo-hydrate  group, 
pyrimidin  and  purin  bases,  especially  adenin  and  guanin.  Then 
follows  the  action  of  ferments  (adenase  and  guanase),  which  remove 
the  amino-group  from  these  purin  bases,  transforming  adenin  into 
hypoxanthin,  and  guanin  into  xanthin  (Jones).  The  deaminiza- 
tion  is  associated  with  hydrolysis.  Thus : 
CgHgNs-h  HjO  =C5H4N40-j-  NH3;  C5H5N6O  +  HgO  =C5H4N402-h  NH3. 

.\denin.  Hypo<niit)iin.  Guanin.  Xanibin. 


METABOLISM  OF  PROTEINS  585 

B5'  oxidation  hypoxanthin  is  changed  into  xanthin  and  xanthin 
into  uric  acid,  and  the  oxidation  seems  to  be  accomphshed  by  a 
separate  oxidizing  fernien"-  xanthin  oxidase,  whose  action  may  be 
thus  represented : 

C5H4N4O  +  O  ^CgHgN/Jg ;  C6H5N4O2  +  O  ^CgHiN^Oj. 

Hypoxanthin.  Xanthin.  Xanthin.  Uric  Acid. 

Evidence  of  the  existence  of  these  ferments,  and  of  their  wide  dis- 
tribution, has  been  obtained  by  making  experiments  on  the  various 
substances  mentioned  with  extracts  of  different  tissues. 

The  portion  of  the  uric  acid  which  comes  from  the  food  (mainly 
from  the  purin  bodies  in  it)  is  sometimes  denominated  the  ex  genoiis 
portion,  while  that  which  arises  from  the  tissues  is  called  the  endog- 
enotis  portion.  The  latter  moiety,  which  generally  amounts  to 
about  0-6  gramme  in  the  twenty-four  hours,  can  be  estimated  by 
restricting  the  diet  to  articles  of  food  free  from  purin  bodies,  such  as 
bread,  milk,  cheese,  eggs,  and  butter.  It  is  stated  that  the  endog- 
enous uric  acid  remains  practically  constant  in  the  same  individual 
under  constant  conditions,  and  is  unaffected  by  changes  in  the  diet. 

The  total  excretion  of  uric  acid  (and  the  other  purin  bodies)  is 
by  no  means  identical  with  the  sum  of  the  uric  acid  taken  in  as 
purin  bases  in  the  food  and  that  produced  in  the  body.  A  con- 
siderable destruction  of  uric  acid  (and  other  purin  bodies)  goes  on 
in  the  body,  and  mainly  in  the  liver.  The  quantity  of  endogenous 
uric  acid  excreted  by  the  Iddneys  bears  a  certain  ratio  to  the  total 
amount  which  has  entered  the  circulation.  This  ratio  varies  much 
in  different  mammalian  species.  In  man  a  full  half  is  said  to  be 
excreted  and  about  a  half  destroyed,  being  mainly  changed  into  urea. 
Some  of  the  exogenous  moiety  is  also  broken  down.  \Vhen  uric  acid 
is  heated  in  a  sealed  tube  with  strong  hydrochloric  acid,  it  is  broken 
up  into  glycin,  carbon  dioxide,  and  ammonia.  There  are  grounds 
for  beheving  that  a  similar  decomposition  takes  place  in  the  body, 
and  that  the  products  are  then  transformed  to  urea  in  the  liver. 

The  process  of  uricolysis,  or  destruction  of  uric  acid,  is  usually 
attributed  to  a  ferment  called  the  uricolytic  ferment,  and  it  has  been 
supposed  that  one  of  the  factors  in  the  production  of  gout  may  be 
a  diminution  in  the  amount  or  activity  of  this  ferment.  In  some 
cases  it  is  said  to  be  entirely  absent.  It  is  doubtful,  however, 
whether  in  man  and  the  anthropoid  apes  the  oxidizing  enzyme, 
uricase  or  uricoxydase,  which  oxidizes  uric  acid  to  allantoin 
(€4115X403),  exists.  In  all  other  mammals  hitherto  investigated  it 
has  been  found  in  some  of  the  tissues.  In  accordance  with  this, 
only  a  trace  of  allantoin  is  present  in  human  urine  and  in  the  urine 
of  the  higher  apes,  while  in  the  other  mammals — for  example,  in 
the  dog — a  large  proportion  of  the  purin  excretion  assumes  this 
form.  It  is  probable  that  there  is  more  than  one  way  in  whicli 
uric  acid  may  be  decomposed  in  the  body,  and,  if  so,  that  there  is 


586  METABOLISM,  NUTRITION  AND  DIETETICS 

more  than  one  ferment  concerned  in  its  transformation.  It  would 
be  well,  therefore,  not  to  speak  of  uricolysis  as  if  it  were  synonymous 
with  the  well-ascertained  process  by  which  allantoin  is  formed 
from  uric  acid,  and  not  to  identify  all  enzymes  which  may  take 
part  in  uricolysis  with  uricoxydase. 

It  is  worthy  of  remark  in  this  connection,  as  a  further  illustration 
of  the  differences  which  may  exist  in  the  purin  metabolism  in 
different  kinds  of  animals,  that  in  man  and  the  anthropoid  apes  the 
quantity  of  purin  bases  in  the  urine  is  small  in  proportion  to  the 
quantity  of  uric  acid.  In  the  pig,  which  is  included  among  the 
animals  that  form  allantoin  from  uric  acid,  the  purin  bases  exceed 
the  uric  acid  in  amount,  whereas  in  the  dog,  which  likewise  excretes 
allantoin,  the  purin  bases  exist  in  very  small  amount  compared 
with  the  uric  acid. 

In  concluding  our  consideration  of  the  metabolism  of  the  nucleic 
acids,  the  question  may  be  raised  whether  it  is  related  to  the  metabo- 
lism of  the  other  substances — carbo-hydrates,  fats,  and  proteins — 
in  such  a  way  that  derivatives  of  nucleic  acid  can  contribute  to  the 
formation  of  any  of  these,  or  derivatives  of  carbo-hydrates,  fats,  or 
proteins  contribute  to  the  formation  of  any  of  the  components  of 
nucleic  acid.  It  has  been  already  mentioned  that  the  phosplioric 
acid  can  aid  in  the  S5mthesis  of  phosphatides,  and  that  the  carbo- 
hydrate groups  probably  take  their  place  in  the  ordinary  carbo- 
hydrate metabolism.  There  is  no  evidence  that  the  purin  bases  can 
take  part  or  can  yield  products  capable  of  taking  part  in  the  forma- 
tion of  any  of  the  other  substances.  The  purin  metaboh'sm,  so  far 
as  is  known,  moves  in  a  closed  circuit.  Of  the  fate  of  the  pyrimidin 
bases  nothing  is  surely  known.  Without  doubt  nucleic  acid  can  be 
formed  in  the  body  when  none  is  contained  in  the  food.  Mc^e  than 
one  source  of  the  phosphoric  acid  and  the  carbo-hydrate  are  known 
and  have  been  already  pointed  out,  but  how  and  from  what  materials 
the  purin  and  pyrimidin  bases  are  formed  cannot  yet  be  stated. 
Recently  the  synthesis  of  nucleosides  has  been  accomplished  in  the 
laboratory  (Fischer).  It  only  needs  the  introduction  of  phosphoric 
acid  in  the  appropriate  way  into  the  molecule  to  give  nucleic  acid. 

The  Significance  of  Kreatin  and  Kreatinin  in  Protein  Metabolism. — 
A  glance  at  the  tables  of  composition  of  the  urine  (p.  471)  will  show 
that  kreatinin,  as  regards  the  quantity  excreted,  is  a  much  more 
important  product  of  nitrogenous  metabolism  than  uric  acid,  stand- 
ing, indeed,  with  the  ammonia  compounds,  next  in  order  to  urea; 
but  our  information  as  to  its  source  and  significance  is  very  scanty. 

Kreatin  is  a-methylguanidin -acetic  acid,  and  kreatinin  is  derived 
from  it  by  loss  of  the  elements  of  water : 

/NH2       /NH2  /NH2  /NH— CO 

C^NH     C<=NH  CH3.COOH  C(  NH  C^NH 

XNHa      \NH.CH3a  \N(CH3).CH2.COOH  \n(CH3).CH2 

Guanidin.        Methylguanidin.    Acetic  acid.  Kreatin.  Kreatinin. 


METABOLISM  OF  PROTEINS  537 

On  heating  with  baryta -water  kreatin  is  decomposed,  yielding  urea, 
mcthylglycocoll  or  sarcosin,  and  other  substances.  It  can  be  prepared 
synthetically  from  sarcosin  and  cyanamid.     Thus: 

/NH2     H.N(CH3)  /NH2 

C^N       +      I  =     C^NH 

CHg.COOH  \N(CH3).CHo.COOH 

Cyanamid.         Methylglycocoll.  ,  Kreatin. 

Kreatin  is  found  in  considerable  amount  (p.  741)  in  muscular 
tissue,  and  in  traces  in  other  tissues  and  in  blood-plasma. 

Kreatinin  can  be  so  readily  obtained  from  kreatin  outside  the 
body  tluit  it  is  tempting  to  suppose  that  the  portion  of  the  kreatinin 
of  the  urine  which  is  not  formed  from  the  kreatin  in  the  food  is 
derived  from  the  kreatin  of  the  muscles  and  other  tissues,  and  many 
theories  have  been  evolved  to  connect  the  kreatinin  of  urine  with 
the  kreatin  of  the  muscles.  But  it  is  doubtful  whether  there  is  any 
direct  connection.  The  alleged  absence  of  kreatinin  from  muscle 
seemed  to  be  opposed  to  the  idea  that  the  kreatin  store  of  the 
muscular  tissue  was  an  important  source  of  urinary  kreatinin;  for 
if  a  constant  transformation  of  this  Idnd  was  going  on,  traces  of 
kreatinin  not  yet  absorbed  by  the  blood  might  have  been  expected 
to  be  present  in  the  muscles.  Recently,  however,  it  has  been 
reported  that  small  quantities  of  kreatinin  do  exist  in  fresh  muscle 
(4  to  8  milligrammes  in  100  grammes  of  tissue),  and  that  when  the 
muscle  is  allowed  to  undergo  autolysis  the  kreatinin  increases  at  a 
very  uniform  rate  at  the  expense  of  the  kreatin.  Added  kreatin 
experiences  the  same  fate  as  the  kreatin  originally  present,  while 
added  kreatinin  inhibits  the  reaction,  or  even  reverses  it  (Myers  and 
Fine).  A  parallelism  with  the  conversion  of  glycogen  into  dextrose 
in  the  liver  easily  suggests  itself,  and  it  is  possible  that  we  are  here 
in  the  presence  of  a  normal  reaction  which  may  account  for  at 
least  a  portion  of  the  kreatinin  excretion.  It  is  probable  that  both 
kreatin  and  kreatinin  can  undergo  changes  in  the  body,  especially 
in  the  liver,  and  it  is  possible  that  the  products  may  be  further 
utilized  in  metabolism.  If  this  were  so,  the  kreatin  store  of  the 
muscles  would  acquire  new  significance  as  a  reserve  of  useful  material 
with  perhaps  a  long  and  varied  metabolic  career  before  it,  and  would 
not  constitute  merely  a  temporar}^  depot  of  waste  material  whose 
metabolic  history  was  ended,  and  which  was  waiting  to  be  excreted. 

However  this  may  be,  the  constancy  of  the  kreatinin  elimination 
on  a  meat-free  diet  (p.  475),  and  its  complete  independence  of  the 
changes  in  the  total  nitrogen  excretion,  show  that  it  has  a  different 
significance  in  protein  metabolism  from  the  urea.  Evidence  is 
accunmlating  that  it  is  especially  in  the  metabolism  of  the  organized 
or  tissue  protein  that  the  product  eventually  excreted  as  kreatinin 
arises;  in  other  words,  that  it  represents  especially  the  nitrogenous 
waste  connected  with  the  wear  and  tear  of  the  bodily  machinery, 
while  urea  represents  also,  and  under  ordinary  conditions  of  diet 


588  METABOLISM,  NUTRITION  AND  DIETETICS 

chiefly,  the  nitrogen  of  the  surplus  amino-acids  which  are  not  utiHzed 
in  the  building  of  new  or  the  repair  of  old  tissue  elements.  The 
fact  that  the  amount  of  kreatinin  excreted  by  different  persons 
seems  to  be  related  to  the  weight  of  active  tissue  in  the  body,  exclud- 
ing fat,  is  in  favour  of  this  suggestion,  and  there  is  other  evidence 
pointing  in  the  same  direction;  for  example,  in  ordinary  circum- 
stances kreatiji  is  either  absent  from  the  urine  or  present  in  very 
small  amoimt,  except  in  young  children.  When,  however,  the  de- 
composition of  tissue-protein  is  abnormally  increased,  as  in  starva- 
tion, in  fevers,  in  woinen  after  delivery,  while  involution  of  the 
uterus  and  the  associated  destruction  of  a  considerable  mass  of 
smooth  muscle  is  taking  place,  kreatin  appears  in  larger  quantities 
in  the  urine,  perhaps  because  it  can  no  longer  be  all  converted  into 
kreatinin.  Now.  the  increased  excretion  of  kreatin  in  starvation 
can  be  prevented  by  giving  carbo-hydrate  food,  which  is  known 
(p.  595)  to  lead  to  sparing  of  tissue-protein  (Mendel  and  Rose). 

The  statement  that  the  content  of  the  urine  in  kreatinin  is  in- 
creased by  muscular  work  may  indicate  that  the  muscular  machine 
wears  out  faster  during  activity  than  during  rest,  or  perhaps  only 
that  already-formed  kreatin  leaves  the  muscles  in  greater  amount 
when  the  blood-flow  is  increased;  but  recent  observations  tend  to 
show  that  this  statement  maj'  require  revision. 

As  to  the  manner  in  which  kreatin  is  changed  into  kreatinin  in 
the  body;  a  highly  suggestive  fact  is  the  presence  of  ferments  in 
various  organs  which  possess  this  power.  Ferments  also  exist 
which  can  decompose  both  kreatin  and  kreatinin.  The  existence 
of  such  enzymes  is  presumptive  evidence  that  the  changes  which 
they  are  capable  of  producing  actually  occur  in  the  organism;  but 
the  seat  of  the  changes  if  they  do  take  place,  and  their  metabolic 
significance,  are  unknown.  Kreatin  when  given  by  the  mouth  or 
injected  into  the  blood  does  not  cause  any  increase  in  the  urinary 
kreatinin,  nor  when  administered  in  moderate  quantities  does  it 
seem  to  be  excreted  as  kreatin.  Kreatinin,  on  the  other  hand, 
when  added  to  the  food,  causes  an  increase  in  the  kreatinin  of  the 
urine. 

Intracellular  Ferments — Autolysis. — As  to  the  agencies  by  which 
the  decomposition  of  the  proteins  is  carried  out  in  the  cells,  we  have 
already  spoken  of  the  oxidizing  cell  ferments,  or  oxydases  (p.  267) .  Re- 
ducing ferments,  or  reductases,  are  also  known,  and  can  be  extracted 
from  most  organs,  if  not  all.  Like  oxydases,  they  act  in  a  weakly 
alkaline  medium,  causing  in  the  presence  of  hydrogen  such  reduc- 
tions as  the  formation  of  nitrites  from  nitrates.  There  is  some 
evidence  that  one  and  the  same  ferment  may  act  as  an  oxydase  or 
a  reductase  according  to  the  conditions.  Recent  researches  have 
brought  to  light  in  addition  hydrolytic  intracellular  ferments,  which 
split  up  proteins  very  much  in  the  same  way  as  the  proteolytic 
ferments  of  the  digestive  juices. 


METABOLISM  OF  PROTEINS  589 

The  significance  of  these  autolytic  enzymes  in  the  normal  metabo* 
hsm  of  proteins  has  been  already  discussed  (p.  569) ;  indeed,  so  many 
of  the  chemical  reactions  of  the  body  have  been  found  to  depend 
upon  enzymes  that  modern  physiology  may  at  first  thought  seem 
almost  to  have  reverted  to  the  position  of  van  Helmont  and  his 
school  in  the  seventeenth  century,  who  resolved  all  difficulties  by 
murmuring  the  magic  word  '  ferment.'  No  fewer  than  eleven  fer- 
ments have  been  stated  to  be  present  and  active  in  the  liver  alone 
— viz.,  a  proteolytic  and  a  nuclein-splitting  ferment,  a  ferment 
which  splits  off  ammonia  from  amino-acids,  a  milk-curdling  ferment, 
a  fibrin  ferment,  a  bactericidal  ferment,  an  oxydase,  a  hpase,  a 
maltase,  a  ferment  called  glycogenase,  which  changes  glycogen  into 
dextrose,  and  an  autolytic  ferment.  In  the  presence  of  such  an 
array  of  enzymes  the  organs  might  seem  to  be  little  more  than 
incubators  in  which  the  ferments  do  their  w^ork.  It  must  not  be 
supposed,  however,  that  the  intracellular  ferments,  whether  they 
cause  decomposition  or  synthesis,  oxidation  or  reduction,  work  in- 
dependently of  what,  for  want  of  a  better  name,  we  must  call  the 
organization  of  the  cell.  We  may  be  sure  they  are  the  servants 
and  not  the  masters  of  the  protoplasm,  and  that  a  drop  of  an  extract 
containing  intracellular  ferments  has  very  different  powers  from  a 
living  cell.  '  It  is  not  in  the  existence  of  the  ferments,  but  in  their 
combined  action  at  the  proper  time  and  in  the  proper  intensity,  that 
the  riddle  of  metabolism  lies  '  (Hober). 

Summary. — At  this  point  let  us  sum  up  what  we  have  learnt  as 
to  the  relation  between  the  proximate  principles  of  the  tissues  and 
the  proximate  principles  of  the  food.  Inside  the  body  we  recognize 
representatives  of  the  three  groups  of  organic  food-substances  in  a 
typical  diet  —  proteins,  carbo-hydrates,  and  fats.  But  we  should 
greatly  err  if  we  were  to  imagine  that  the  three  streams  of  food- 
materials  have  flowed  from  the  intestines  into  the  tissues  each  in  its 
separate  channel,  neither  giving  to  nor  taking  from  the  others. 
The  fats  of  the  body  may,  indeed,  in  part  be  composed  of  molecules 
which  were  present  as  fat  in  the  food  ;  but  they  may  also  be  formed 
from  carbo-hydrates,  and  probably  from  proteins.  The  carbo-hydrates 
of  the  body — the  glycogen  of  the  liver  and  muscles,  the  sugar  of  the  blood 
— may  undoubtedly  be  derived  from  carbo-hydrates  in  the  food,  but  they 
may  also  be  derived  from  proteins  and  from  fats  {certainly  from  their 
glycerin  constituent,  perhaps  from  the  fatty  acids  as  well).  The  pro- 
teins of  the  body  come  mainly,  if  not  solely,  from  the  proteins  of  the  food. 
Although,  of  course,  neither  fats  nor  carbo-hydrates  can  by  themselves 
form  protein,  being  devoid  of  nitrogen,  it  is  possible  that  products 
arising  in  the  intermediary  metabolism  of  either  may,  by  combining 
with  nitrogenous  groups,  be  transformed  into  amino-bodies,  which  can 
then  take  part  in  the  synthesis  of  proteins.  In  any  case  there  is  no 
doubt  that  both  carbo-liyd rates  and  fats  can  economize  proteins  and 
shield  them  from  an  overhasty  metabolism. 


590 


METABOLISM,  NUTRITION  AND  DIETETICS 


Section  IV. — Statistics  of  Nutrition — ^The  Income  and 
Expenditure  of  the  Body  in  Terms  of  Matter* 

Preliminary  Data. — The  office  of  the  food  is  to  maintain  the  con- 
stituents of  the  body  upon  the  whole  in  their  normal  proportions.  A 
knowledge  of  the  chemical  composition  of  the  body  is,  therefore,  an 
important  datum  in  the  consideration  of  the  statistics  of  its  metabolism. 
The  body  of  a  man  analyzed  by  Volkmann  had  the  following  composition  : 

'Water     -         -         -         -  65'9  per  cent. 
Mineral  matter        -         -    4-4        ,, 

{Carbon       1 8 -4  per  cent. "j 
Hydrogen    27         ,,         I 
Nitrogen      2-6         ,,         f  297 
Oxygen        6-0         ,,        J 

The  muscles,  the  adipose  tissue,  and  the  skeleton  form  nearly  four- 
fifths  of  the  total  body-weight  in  the  adult.  The  following  table  shows 
the  percentage  amount  of  each  of  these  tissues  in  a  man,  a  woman,  and 
a  child  (Bischoff) : 


Inorganic  substances 


Organic  substances 


Man. 

Woman. 

New-born 
Child. 

Voluntary  muscles 
Adipose  tissue     - 
Skeleton      -         -         - 
Rest  of  body 

41-8 
l8-2 

15-9 
24-1 

35-8 

28-2 
20'9 

23-5 
13-5 
157 
47-3 

The  nitrogen  is  contained  chiefly  in  the  muscles,  glands,  and  nervous 
system,  and  in  the  constituents  of  the  connective  tissues,  which  yield 
gelatin,  various  mucoids,  and  elastin.  The  ordinary  proteins  make  up 
about  9  per  cent,  of  the  weight  of  the  body,  or  22  per  cent,  of  its  solids; 
the  albuminoids  or  sclero-proteins  (gelatin-yielding  material,  etc.)  (p.  2) 
about  6  per  cent,  of  the  body-weight.  Nitrogen  exists  in  proteins  to 
the  extent  of  16  per  cent.,  so  that  the  6*5  kilos  of  protein  of  a  70-kilo 
body  contain  about  i  kilo  of  nitrogen. 

The  carbon  is  contained  chiefly  in  the  fat,  which  forms  a  very  large 
proportion  of  the  water-free  substance  of  the  body,  and  in  the  proteins. 
A  small  amount  is  present  as  calcium  carbonate  in  the  bones.  In  the 
body  of  a  strong  young  man  weighing  68*6  kilos,  Voit  found  the  following 
quantities  of  dry  fat  in  the  various  tissues : 

Adipose  tissue  -         .         .         .         .  8809*4  grammes. 

Skeleton  _-.--_  2617-2 

Muscles  _...--  636-8         ,, 

Brain  and  spinal  cord  -         -         -         -  226-9         ,, 

Other  organs      ------         ■73-2         ,, 

Total 12363-5 

equivalent  to  18  per  cent,  of  the  whole  body-weight,  or  44  per  cent,  of 
the  solids.  In  dry  fat  rather  more  than  75  per  cent,  of  carbon  is  present, 
and  in  protein  about  50  to  55  per  cent. ;  so  that  while  the  fat  of  the  body 
analyzed  by  Voit  contained  more  than  9  kilos  of  carbon,  only  about  a 
third  of  this  amount  would  be  found  in  the  proteins. 

*  The  income  and  expenditure  of  the  body  in  terms  of  energy  are  considered 
in  Chapter  XII. 


STATISTICS  OF  NUTRITION  591 

In  the  fat  there  is,  rouglily  speaking,  12  per  cent,  of  hydrogen,  in 
proteins  only  7  per  cent.;  so  that  from  three  to  four  times  as  much 
hydrogen  is  contained  in  the  fat  of  the  body  as  in  its  proteins. 

Oxygen  forms  about  12  per  cent,  of  fat,  and  20  to  24  per  cent,  of 
proteins;  the  protein  constituents  of  tlie  body,  therefore,  contain  about 
as  much  of  its  oxygen  as  the  fat. 

Of  the  inorganic  salts,  calcium  phosphate,  Ca3(P04)2,  is  much  the 
most  abundant,  owing  to  the  large  amount  of  it  in  bone,  in  the  ash  of 
which  it  is  found  to  the  extent  of  83  per  cent.,  along  with  13  per  cent, 
of  calcium  carbonate.  . 


Income  and  Expenditure  of  Nitrogen — The  Nitrogen 
Balance-Sheet. 

Nitrogenous  Equilibrium. — It  is  a  matter  of  common  experi- 
ence that  the  weight  of  the  body  of  an  adult  may  remain  approxi- 
mately constant  for  many  months  or  years,  even  when  the  diet  varies 
greatly  in  nature  and  amount.  And  not  only  may  the  weight  remain 
constant,  but  the  relative  proportions  of  the  various  tissues  of  the 
body,  so  far  as  can  be  judged,  may  remain  constant  too.  Here  it 
is  evident  that  the  expenditure  of  the  body  must  precisely  balance 
its  income:  it  must  lose  as  much  nitrogen  as  it  takes  in,  otherwise 
it  would  put  on  flesh ;  it  must  lose  as  much  carbon  as  it  takes  in, 
otherwise  it  would  put  on  fat.  Or,  again,  the  body  may  be  losing 
or  gaining  fat,  giving  off  more  or  less  carbon  than  it  receives,  while 
its  '  flesh  '  (its  protein  constituents)  remains  constant  in  amount, 
the  expenditure  of  nitrogen  being  exactly  equal  to  the  income.* 
In  both  cases  we  say  that  the  body  is  in  nitrogenous  equilibrium. 

A  starving  animal  or  a  fever  patient,  on  the  other  hand,  is  living 
upon  capital,  the  former  entirely,  the  latter  in  part ;  the  expenditure 
of  nitrogen  is  greater  than  the  income.  A  growing  child  is  living 
below  its  income,  is  increasing  its  capital  of  flesh.  In  neither  case 
is  nitrogenous  equilibrium  present. 

The  starving  animal,  as  long  as  Hfe  lasts,  excretes  urea,  kreatinin, 
and  other  nitrogenous  substances,  and  gives  off  carbon  dioxide; 
but  its  expenditure,  and  especially  its  expenditure  of  nitrogen,  is 
pitched  upon  the  lowest  scale.  It  lives  penuriously,  it  spins  out 
its  resources;  its  glycogen  goes,  its  fat  goes,  a  certain  part  of  its 
protein  goes,  and  when  its  weight  has  fallen  from  25  to  50  per  cent, 
it  dies.  At  death  the  heart  and  central  nervous  sj'stem  are  found 
to  have  scarcely  lost  in  weight ;  the  other  organs  have  been  sacrificed 
to  feed  them.  Fig.  199  shows  the  percentage  loss  of  weight  and 
the  proportion  of  the  total  loss  which  falls  upon  each  of  the  organs 
of  a  cat  in  starvation  (Voit). 

*  For  long  experiments  extending  over  many  days  the  nitrogen  balance 
may  be  considered  as  practically  the  same  as  the  protein  balance,  but  this 
is  not  necessarily  true  of  short  periods  of  time,  since  the  stock  of  nitrogen 
present  in  the  body  in  other  forms  than  proteins,  although  relatively  small, 
is  subject  to  variations. 


592  METABOLISM,  NUTRITION  AND  DIETETICS 

For  the  first  day  of  starvation  the  excretion  of  urea  in  a  dog  or 
cat  is  not  diminished;  it  takes  about  twenty-four  hours  for  all  the 
nitrogen  corresponding  to  the  proteins  of  the  last  meal  to  be  elimin- 
ated. On  the  second  day  the  quantity  of  urea  sinks  abruptly; 
then  begins  the  true  starvation  period,  during  which  the  daily  output 
of  urea  remains  constant  or  diminishes  very  slowly  until  a  short  time 
before  death,  when  it  rapidly  falls,  and  soon  ceases  altogether.  An 
increase  in  the  excretion  may  precede  the  final  abrupt  decline  (pre- 
mortal increase).  This  seems  to  indicate  the  time  at  which  all  the 
available  fat  has  been  used  up,  and  after  which  protein  is  no  longer 
'  spared  '  by  the  fat.*  If  the  animal  has  little  fat  in  its  body  to 
begin  with,  the  rise  in  the  urea  excretion  takes  place  even  after  the 
first  few  days.      So  long  as  the  fat  lasts  the  rate  at  which  it  is 


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Fig.  199. — Diagram  showing  Loss  of  Weight  of  the  Organs  in  Starvation.  The 
numbers  under  I.  are  the  percentages  of  the  total  loss  of  body-weight  borne  by 
the  various  organs  and  tissues.  The  numbers  under  II.  give  the  percentage  loss 
of  weight  of  each  organ  calculated  on  its  original  weight  as  indicated  by  com- 
parison with  the  organs  of  a  similar  animal  killed  in  good  condition. 

destroyed — as  estimated  froiji  the  amount  of  carbon  given  off  minus 
the  carbon  corresponding  to  the  broken-down  proteins — ^remains 
very  nearly  constant  after  the  first  day.  The  fat  to  a  certain  extent 
economizes  the  proteins  of  the  starving  body,  but  however  much 
fat  may  be  present,  a  steady  waste  of  the  tissue-proteins  goes  on. 
If  non-nitrogenous  food  in  the  form  of  sugar  is  supplied  to  an  other- 
wise starving  animal,  the  premortal  rise  in  the  nitrogen  excretion 
does  not  occur.  By  giving  a  sufficient  quantity  of  sugar,  or  of 
sugar  and  fat,  but  practically  no  protein  (so-called  nitrogen  starva- 
tion), the  excretion  of  nitrogeii  may  be  reduced  to  one-third  of  its 
amount  when  no  food  at  all  is  given.     This  is  true  both  in  animals 

*  If  the  animal  has  been  for  some  time  on  a  diet  containing  an  abundance 
of  proteins,  several  days  may  elapse  before  the  constant  excretion  of  urea 
is  reached;  if  the  previous  diet  has  been  poor  in  protein,  the  constant  star- 
vation output  may  be  at  once  established. 


STATISTICS  OF  NUTRITION 


593 


and  man  In  this  way  the  daily  excretion  of  nitrogen  in  a  man  has 
been  reduced  to  4  grammes.  It  is  a  remarkable  fact  that  while  a 
mixture  of  carbo-hydrate  and  fat  will  act  just  as  well  as  carbo- 
hydrate alone  in  bringing  about  this  reduction  in  the  hitrogen 
output,  fat  without  carbo-hydrate  is  much  less  effective.  The 
hypothesis  suggested  by  Landergren  to  explain  this  is  alluded  to 
on  another  page  (p.  542). 

The  results  obtained  on  fasting  men  differ  in  some  respects  from 
those  obtained  on  starving  animals.  In  ten  days  of  hunger,  Cetti, 
a  professional '  fasting  man  '  of  meagre  habit,  excreted  112  grammes 
nitrogen,  or  an  average  of  11  grammes  a  day.  The  excretion  was 
least  on  the  eighth,  ninth,  and  tenth  days — namely,  about  9  grammes 
a  da5^  On  the  third  day  it  was  higher  than  on  the  second,  and 
almost  as  high  on  iSgrams 
the  fourth  as  on  the 
third.  A  similar  rise 
in  the  nitrogen  lo^naros 
excretion  on  the 
second  day  has  been 
observed  in  other  "5  grams 
fasting  men,  but  is 
either  rare  or  absent 
in  fasting  dogs.  The 
explanation  appar- 
ently is  that  in  the 
ordinary  food  of 
man  there  is  a 
greater  abundance 
of  carbo  -  hydrates 
and  fats,  the  pro- 
tein -  sparing  action 
of    which    is    most 


; 


Ai5 

e>6 


A4^5 
6)16 


A60 


Bf4£ 


A50 
^1 

Fig.  200. — Excretion  of  Urea  in  Starvation.  A  is  a  curve 
representing  the  quantity  of  urea  excreted  daily  by  a 
fat  dog  in  a  starvation  period  of  sixty  days.  B  is  the 
curve  of  urea  excretion  in  a  lean  young  dog  in  a 
starvation  period  of  twenty-four  days.  Both  are  con- 
structed from  Falck's  numbers,  but  in  A  only  every 
third  day  is  put  in,  in  order  to  save  space.  The  num- 
bers along  the  vertical  axis  represent  grammes  of  m-ea; 
those  along  the  horizontal  axis  days  from  the  beginning 
of  starvation. 


pronounced  at  the  very  beginning  of  the  starvation  period.  The 
quantity  of  chlorine  and  alkalies  in  the  urine  was  also  diminished, 
while  the  phenol  was  increased.  The  respiratory  quotient  sank  to 
0-66  to  0-69 — even  less  than  the  quotient  corresponding  to  oxida- 
tion of  fats  alone.  The  meaning  of  this,  in  all  probability,  is  that 
some  of  the  carbon  of  the  broken-down  proteins  was  laid  up  in  the 
body  as  glycogen  (Zuntz).  In  another  professional  fasting  man 
(Succi)  with  a  considerable  amount  of  body-fat,  the  excretion  of 
nitrogen  was  found  to  diminish  continuously  during  a  fast  of  thirty 
days,  being  less  than  7  grammes  on  the  tenth  day.  In  another  fast 
of  twenty-one  days  by  the  same  person  it  was  a  little  less  than 
3  grammes  on  the  last  day.  The  surprisingly  small  nitrogenous 
waste  in  this  case  is  perhaps  to  be  accounted  for  by  the  protein- 
sparing  action  of  the  abundant  body-fat.     The  nitrogenous  metabo- 


594 


METABOLISM,  NUTRITION  AND  DIETETICS 


lism  has  also  been  investigated  during  long-continued  hypnotic  sleep 
(Hoover  and  Sollmann).  The  results  were  very  much  the  same  as 
in  an  ordinary  starvation  experiment. 

It  might  be  supposed  that  if  an  animal  was  given  as  much  nitrogen 
in  the  food  in  the  form  of  proteins  as  corresponded  to  its  daily  loss 
of  nitrogen  during  starvation,  this  loss  would  be  entirely  prevented 
and  nitrogenous  equilibrium  restored.  The  supposition  would  be 
very  far  from  the  reality.  If  a  dog  of  30  kilos  weight,  which  on 
the  tenth  day  of  starvation  excreted  11-4  grammes  urea,  had  then 
received  a  daily  quantity  of  protein  equivalent  to  this  amount — 
that  is  to  say,  about  34  grammes  of  dry  protein,  or  175  grammes  of 
lean  meat — ^the  excretion  of  nitrogen  would  at  once  have  leaped 
up  to  nearly  double  its  starvation  value.  If  the  quantity  of  protein 
in  the  diet  was  progressively  increased,  the  output  of  urea  would 
increase  along  with  it,  but  at  an  ever-slackening  rate;  and  at  length 
a  condition  would  be  reached  in  which  the  income  of  nitrogen 
exactly  balanced  the  expenditure,  and  the  animal  neither  lost  nor 
gained  flesh. 

In  an  experiment  of  Voit's,  for  instance,  the  calculated  loss  of  flesh 
in  a  dog  with  no  food  at  all  was  igo  grammes  a  day.  The  animal  was 
now  fed  on  a  gradually  increasing  diet  of  lean  meat,  with  the  following 
result : 


Flesh  in  the 

Flesh  used  up  in 

Net  Loss  ol 

Food. 

the  Body. 

Body-flesh. 

0 

190 

190 

250 

341 

91 

3.SO 

411 

61 

400 

454 

54 

45f 

471 

21 

480 

492 

12 

1 

The  loss  of  nitrogen  in  the  urine  and  faeces  is  what  was  measured. 
Knowing  the  average  composition  of  '  body-flesh  '  (muscles,  glands, 
etc.),  it  is  possible  to  translate  results  stated  in  terms  of  nitrogen  into 
results  stated  in  terms  of  '  flesh.'  Muscle  contains  approximately 
3-4  per  cent,  of  nitrogen.  Here,  with  a  diet  of  480  grammes  of  meat,  the 
dog  was  still  losing  a  little  flesh;  it  would  probably  have  required  from 
500  to  600  grammes  for  equilibrium.  The  results  are  graphically 
repr».sented  in  Fig.  201,  p.  596. 

The  quantity  of  protein  food  necessary  for  nitrogenous  equili- 
brium varies  with  the  conchtion  of  the  organism;  an  emaciated  body 
requires  less  than  a  muscular  and  well-nourished  body.  The  least 
quantity  which  would  suffice  to  maintain  in  nitrogenous  equilibrium 
the  famous  35  kilo  dog  of  Voit,  even  in  very  meagre  condition,  was 
480  grammes  of  lean  meat,  corresponding  to  16  grammes  of  nitrogen, 
or  35  grammes  of  urea — that  is,  about  three  times  the  daily  loss 


STATISTICS  OF  NUTRITION  595 

during  starvation.  From  this  lower  limit  up  to  2,500  grammes  of 
meat  a  day  nitrogenous  equilibrium  could  always  be  attained,  the 
animal  putting  on  some  flesh  at  each  increase  of  diet,  until  at  length 
the  whole  2,500  grammes  was  regularly  used  up  in  the  twenty-four 
hours.  A  further  increase  was  only  checked  by  digestive  troubles. 
A  man,  or  at  least  a  civilized  man,  can  consume  a  much  smaller 
amount  both  absolutely  and  in  proportion  to  the  body-weight. 
Rubner,  with  a  body-weight  of  yz  kilos,  was  able  to  digest  and  absorb 
over  1,400  grammes  of  lean  meat;  Ranke,  with  about  the  same 
body-weight,  could  only  use  up  1,300  giimmes  on  the  first  day  of 
his  experiment,  and  less  than  1,000  grammes  on  the  third.  But 
whether  the  surplus  of  protein  food  above  the  necessary  minimum 
is  great  or  small,  nitrogen  equilibrium  is  eventually  attained,  and 
thereafter  all  the  nitrogen  of  the  food  regularly  appears  in  the 
excreta;  the  explanation  of  this  fact  will  be  considered  a  little 
later  (p.  598). 

So  much  for  a  purely  protein  diet.  When  fat  is  given  in  addition 
to  protein,  nitrogenous  equilibrium  is  attained  with  a  smaller  quantity 
of  the  latter.  A  dog  which,  with  protein  food  alone,  is  putting  on 
flesh,  will  put  on  more  of  it  before  nitrogenous  equiUbrium  is  reached 
if  a  considerable  quantity  of  fat  be  added  to  its  diet.  Fat,  therefore, 
economizes  protein  to  a  certain  extent,  as  we  have  already  recog- 
nized in  the  case  of  the  starving  animal.  On  the  other  hand,  when 
protein  is  given  in  large  quantities  to  a  fat  animal,  the  consumption 
of  fat  is  increased ;  and  if  the  food  contains  little  or  none,  the  body- 
fat  will  diminish,  while  at  the  same  time  '  flesh  '  may  be  put  on. 
The  Banting  cure  for  corpulence  consists  in  putting  the  patient 
upon  a  diet  containing  much  protein,  but  little  fat  or  carbo-hydrate; 
and  the  fact  just  mentioned  throws  light  upon  its  action. 

All  that  we  have  here  said  of  fat  is  true  of  carbo-hydrates.  To  a 
great  extent  these  two  kinds  of  food  substances  are  complementary. 
Carbo-hydrates  economize  proteins  as  fat  does,  but  to  a  greater 
extent,  so  that  with  an  abundant  supply  of  carbo-hydrate  in  the 
food  the  minimum  protein  requirement  can  be  forced  down  much 
below  what  is  possible  on  a  diet  of  protein  and  fat  alone.  Carbo- 
hydrates also  economize  fat,  so  that  when  a  sulflcicnt  quantity  of 
starch  or  sugar  is  given  to  an  otherwise  starving  animal,  all  loss  of 
carbon  from  the  body,  except  that  which  goes  off  in  the  urea,  krea- 
tinin,  etc.,  still  excreted,  can  be  prevented.  Of  course,  the  animal 
ultimately  dies,  because  the  continuous,  though  diminished,  loss  of 
protein  cannot  be  made  good.  The  fact  that  carbo-hydrates  econo- 
mize proteins  so  much  more  efficiently  than  fat  indicates  that  sugar 
is  essential  in  the  bodily  metabolism,  so  that  when  carbo-hydrates 
are  absent  from  the  food  some  of  the  protein  must  be  broken  down 
so  as  to  yield  eventually  the  compounds  necessary  for  the  formation 
of  carbo-hydrate.     It  is  probable,  indeed,  that  purified  proteins, 


596 


METABOLISM,  NUTRITION  AND  DIETETICS 


Grarr)5 
Soo 

300 
zoo 


100 


\ 

\  ' 

,.., 

\ 

100    jp 


absolutel}'  free  from  admixture  with  carbo-hydrates,  which,  of 
course,  is  not  the  case  with  the  natural  protein  foods,  will  not  per- 
manently suffice  for  nutrition,  but  that  the  protein  must  be  supple- 
mented by  a  certain  amount  of  carbo- 
hydrate in  some  form  available  for  the 
tissues.  It  would  appear,  indeed,  that 
fats  are  not  absolutely  indispensable 
either  for  maintenance  or  for  growth. 
White  rats  have  been  seen  to  grow  nor- 
mally over  long  periods  with  dietaries 
devoid  of  fat ;  for  example,  mixtures  of  the 
purified  protein  edestin  (from  hemp  seed) 
or  casein  with  starch,  sugar,  and  '  protein- 
free  milk  '  freed  from  fat  by  extraction 
with  ether  (Osborne  and  Mendel).  While 
in  these  experiments  the  food  might  not 
have  been  free  from  the  so-called  '  lipoids,' 
it  has  been  demonstrated  that  an  impor- 
tant group  of  substances  of  this  class,  the 
phosphatides,  can  be  synthesized  in  the 
body,  the  necessary  phosphorus  being  ob- 
tainable even  from  inorganic  phosphates 
(McCollom). 

Relation  between  Nitrogen  excreted  and 
the  Quantity  of  Protein  Food. — At  this 
point  we  may  consider  a  little  more 
closely  a  phenomenon  already  alluded  to, 
and  to  which  much  discussion  used  to  be 
devoted  by  writers  on  metabolism.  It 
has  been  stated  that  within  the  limits  of 
nitrogenous  equilibrium,  which  is  the  nor- 
mal state  of  the  healthy  adult,  the  body 
lives  up  to  its  income  of  nitrogen;  it  lays 
by  nothing  for  the  future.  In  the  actual 
pinch  of  starvation  the  organism,  when 
its  behaviour  is  tested  by  a  comparison 
of  the  intake  and  excretion  of  nitrogen, 
appears  to  have  become  suddenly  econo- 
mical. When  a  plentiful  supply  of  protein 
is  presented  to  the  starving  body,  it  seems, 
judged  by  the  same  criterion,  to  pass  at 
once  from  extreme  frugality  to  luxury. 
Some  flesh  may  be  put  on  for  a  short  time,  some  nitrogen  may  be 
stored  up;  but  the  excretion  of  nitrogen  is  soon  adjusted  to  the  new 
scale  of  supply,  and  the  protein  income  is  apparently  spent  as  freely 
as  it  is  received.     These  facts  were  usually  summed  up  in  the 


Fig.  201.  -Curves constructed 
lo  illustrate  Nitrogenous 
Equilibrium  (from  an  Ex- 
periment of  Voit's).  The 
loss  of  flesh  in  grammes  is 
laid  off  along  the  horizontal 
axis.  The  income  and 
expenditure  corresponding 
to  a  gis'en  loss  are  laid  off 
(in  granmies  of  'flesh') 
along  the  vertical  axis.  The 
continuous  curve  is  the 
curve  of  income;  the  dotted 
curve,  of  oxjienditure.  With 
no  income  at  all  the  expen- 
diture is  190  grammes; 
with  au  income  of  480 
grammes  the  expenditure 
is  492  and  the  loss  la 
grammes.  Nitrogenous 
equilibrium  is  represented 
as  being  reached  with  an 
income  of  about  530 
grammes;  here  the  two 
curves  cut  one  another. 


STATISTICS  OF  NUTRITION  597 

dictum,  often  dignified  as  a  '  law  '  of  nitrogenous  metabolism  that : 
Consumption  of  protein  is  largely  determined  by  supply  (Practical 
Exercises,  p.  693). 

To  explain  this  many  hypotheses  were  invented.  The  famous  theory 
of  Voit  aPKiimcd  that  the  food-protein  after  absorption  (the  so-called 
'  circulating-protein  ')  is  carried  to  the  tissues  and  taken  up  by  the 
cells,  whtre  the  greater  part  of  it,  without  lieing  incorporated  with  the 
protoplasm,  is  nevertheless  acted  upon,  rendered  unstable,  shaken  to 
pieces,  as  it  were,  by  the  whirl  of  life  (by  the  intracellular  enzymes  we 
might  now  say  less  dramatically)  in  the  organized  framework,  the 
interstices  of  which  it  fills. 

Pfliiger.  on  the  other  hand,  maintained  that  we  have  no  right  to 
draw  a  distinction  between  the  consumption  of  organ-  and  circulating- 
protein;  that  the  whole  of  the  latter  ultimately  rises  to  the  height  of 
organ-  or  tissue-protein,  and  passes  on  to  the  downward  stage  of 
metabolism  only  through  the  topmost  step  of  organization.  An  increase 
in  the  supply  of  nitrogenous  material  in  the  blood  must,  on  this  view, 
be  accompanied  with  an  increased  tendency  to  the  break-up,  the  dis- 
sociation, as  Pfliiger  put  it,  of  the  living  substance.  The  actual  organ- 
ized elements,  however,  the  existing  cells,  were  not  supposed  to  be 
destroyed;  the  building  remained,  for  although  stones  were  constantly 
crumbling  in  its  walls,  others  were  being  constantly  built  in. 

A  much  less  plausible  view  was  that  the  tissue  elements  themselves  are 
short-lived ;  that  the  old  cells  disappear  bodily  and  are  replaced  by  new 
cells;  and  that  the  whole  of  the  proteins  of  the  food  take  part  in  this 
process  of  total  ruin  and  reconstruction.  Histological  evidence,  as  soon 
as  the  methods  of  examining  tissues  with  the  microscope  became 
sufficiently  refined,  told  strongly  against  this  idea.  Although  the  cells 
of  certain  glands,  such  as  the  mammary,  perhaps  the  mucous  glands, 
and  especially  the  sebaceous  glands  (p.  556),  exhibit  changes  which, 
hastily  interpreted,  might  seem  to  indicate  that  they  break  down 
bodily,  as  an  incident  of  functional  activity,  no  proof  could  be  obtained 
of  the  production  of  new  cells  on  the  immense  scale  which  this  theory 
would  require.  The  relatively  small  and  constant  amount  of  the 
endogenous  metabolism  indicates  that  the  actual  protoplasmic  sub- 
stance, the  living  framework  of  the  cell,  is  comparatively  stable; 
that  it  docs  not  break  down  rapidly;  and  that  only  a  small  and 
fairly  constant  amount  of  food-  or  circulating-protein,  or  of  the 
decomposition  products  of  protein,  is  required  to  supply  the  waste 
of  the  organ-protein. 

We  have  referred  to  these  theories  because  there  could  scarcelj'  be  a 
more  instructive  instance  of  the  way  in  which  theories  become  obsolete 
with  the  advance  of  knowledge  anel  of  the  way  in  which,  with  tl.e 
advance  of  knowledge,  a  phenomenon  which  appears  an  absolute  riddle 
to  one  generation  may  become  fairlj-  intelligible  to  the  next,  perhaps 
childishly  simple  to  a  third.  The  student  will  not  derive  much  benefit 
from  the  perusal  of  this  page  should  he  fail  to  recognize  that  the 
hypotheses  of  the  twentieth  century  arc  mortal  too,  and  bound  for  the 
same  bourne  as  those  of  the  nineteenth. 

It  is  apparent  in  the  first  place  from  our  study  of  the  metabolism 
of  the  proteins  that  the  conclusion,  '  consumption  of  protein  is  pro- 
portional to  supply,'  cannot  be  drawn  from  the  equality  of  nitrogen 
intake  and  nitrogen  output.  The  amino-acids  derived  from  proteins, 
except  that  relatively  small  fraction  employed  in  repairing  the 


598  METABOLISM,  NUTRITION  AND  DIETETICS 

waste  of  the  tissues,  which  in  nitrogen  equihbrium  is  exactly  com- 
pensated for  by  a  corresponding  release  of  amino-acids  or  their 
equivalent  from  the  cell-proteins,  are  indeed  speedily  deaminated 
and  the  nitrogen  of  the  amino-groups  excreted  as  urea  (with 
ammonia  compounds  and  kreatinin).  But,  as  we  have  seen,  only  a 
small  proportion  of  the  chemical  energy  of  the  amino-acids  and  only 
a  small  fraction  of  their  carbon  are  liberated  in  this  process.  The 
carbon-containing  residues  are  katabolized  only  to  the  extent  re- 
quired by  the  momentary  needs  of  the  tissues,  any  balance  being 
stored  as  part  of  the  reserve  of  carbo-hydrate  or  of  fat.  The  body 
does  not  possess  the  means  of  storing  surplus  amino-acids  as  such 
or  even  in  the  form  of  proteins,  except  to  the  small  extent  corre- 
sponding to  any  increase  which  may  occur  in  the  body-protein 
when  the  food-protein  is  increased  beyond  the  minimum  required 
for  nitrogen  equilibrium.  Why  the  organism  has  not  developed 
the  capacity  to  store  large  quantities  of  protein  is,  of  course,  an 
interesting  question,  but  it  need  scarcely  be  discussed  here.  One 
obvious  reason  is  that  protein  is  not  a  suitable  source,  nor  are  amino- 
acids  apparently  a  suitable  source  of  energy  for  the  tissues  until 
they  have  been  deaminated  and  have  probably  undergone  further 
decomposition  and  transformation.  Therefore  they  are  decomposed 
at  once  and  their  available  residue  stored,  if  it  is  in  any  case  to  be 
stored,  in  the  more  available  form  of  carbo-hydrate  (or  fat). 
Where  the  food-proteins  differ  greatly  from  the  body-proteins  in 
the  proportions  of  the  various  amino-acids,  there  would  be  no  object 
in  storing  a  great  surplus  of  those  which  are  most  plentiful  in  the 
food,  if  they  were  at  the  same  time  the  scarcest  in  the  tissues,  or, 
in  the  case  of  gland-cells,  the  scarcest  in  the  proteins  which  they 
manufacture  for  their  secretions. 

At  any  moment  the  magnitude  of  this  non-utilizable  surplus  will 
depend  upon  the  quantity  of  that  one  of  the  indispensable  amino- 
acids  which  is  present  in  the  smallest  amount.  For  the  proper 
proportion  must  be  preserved  between  the  different  '  stones  '  out  of 
which  the  molecule  is  built.  When  a  single  amino-acid  is  intro- 
duced into  the  body,  it  is  at  once  changed  into  urea  and  excreted, 
since  it  cannot  be  utilized  by  itself  for  building  up  protein. 

When  the  cells  have  once  culled  from  the  mixture  circulating  in 
the  blood  the  amino-acids,  a  full  supply  of  which  they  have  most 
difficulty  in  obtaining,  a  residue,  large  or  small,  according  to  the 
quantity  and  quality  of  the  protein  intake,  will  be  left,  and  this  can 
only  be  utilized  to  supph^  energy  or  to  add  to  the  fat  and  carbo- 
hydrate stores.  For  these  uses  removal  of  the  amino-group  is  an 
essential  preliminary.  The  question  whether  the  deamination  of  a 
large  part  of  the  amino-acids  coming  from  the  intestine  takes  place 
in  the  liver,  so  that  the  surplus  nitrogen  is  shunted  out  of  the  main 
metabolic  current  at  its  very  source,  has  been  already  touched  upon 


STATISTICS  OF  NUTRITION  599 

(P-  578)-  Some  writers  conceive  that  in  such  a  short-cut  from  pro- 
tein to  urea  we  have  a  kind  of  physiological  safety-valve  to  protect 
the  tissues  from  the  burden  of  an  excessive  metabolism.  And  ii 
by  this  is  meant  that  it  is  advantageous  to  the  tissues  that  a  special 
mechanism  should  exist  to  eliminate  a  surplus  of  nitrogen  which  they 
do  not  require,  and  which  they  cannot  store,  and  to  present  them 
with  a  residue  which  they  can  utilize,  the  conception  is  certainly 
correct.  But  there  is  no  good  evidence  that  in  the  presence  of  an 
over-abundant  supply  of  amino-acids  the  endogenous  protein  meta- 
bohsm  would  be  essentially  modified. 

Relation  of  Nitrogenous  Metabolism  to  Muscular  Work. — This  is 
another  of  those  classical  physiological  problems  which  it  is  difficult 
to  present  properly  apart  from  its  historical  setting.  The  general 
result  of  much  experimental  work  and  long-continued  discussion  is 
that  when  the  work  does  not  transgress  what  may  be  called  '  normal 
limits,'  the  excretion  of  nitrogen  is  nearly  independent  of  mus- 
cular work — that  is  to  say,  the  quantity  of  nitrogen  excreted  by  a 
man  on  a  given  diet  is  practically  the  same  whether  he  rests  or  works. 
Before  this  was  known  it  was  maintained  by  Liebig  that  proteins 
alone  could  supply  the  energy  of  muscular  contraction — that,  in 
fact,  proteins  were  solely  used  up  in  the  nutrition  and  functional 
activity  of  the  nitrogenous  tissues,  while  the  non-protein  food 
yielded  heat  by  its  oxidation.  As  exact  experiments  multiplied,  it 
was  found  that  muscular  work,  the  production  of  which  is  the 
function  of  by  far  the  greatest  mass  of  protein-containing  tissue, 
had  little  or  no  effect  upon  the  excretion  of  urea  in  the  urine.  More 
than  this,  it  was  shown  that  a  certain  amount  of  work  accomplished 
(by  Fick  and  Wislicenus  in  climbing  a  mountain)  on  a  non-nitrog- 
enous diet  had  double  the  heat  equivalent  of  the  whole  of  the  pro- 
tein consumed  in  the  body,  as  estimated  by  the  urea  excreted  during, 
and  for  a  given  time  after,  the  work.  On  the  assumption  that  all 
the  urea  corresponding  to  the  protein  broken  down  was  eliminated 
during  the  time  of  this  experiment,  a  part  at  least  of  the  work  must 
have  been  derived  from  the  energy  of  non-nitrogenous  material. 
And  other  experiments  in  which  account  was  taken  of  the  increase 
in  the  carbon  dioxide  given  off  (as  conspicuous  an  accompaniment 
of  muscular  work  as  tlie  constancy  of  the  urea  excretion),  showed 
that  during  muscular  exertion  carbonaceous  substances  other  than 
proteins — that  is  to  say,  fats  and  carbo-hydrates — are  oxidized  in 
gi  eater  amount  than  during  rest. 

So  the  pendulum  of  physiological  orthodoxy  came  full-swing  to  the 
olher  side.  Liebig  and  his  school  had  taught  that  proteins  alone  were 
consumed  in  functional  activity;  the  majority  of  later  physiologists 
following  Voit  denied  to  the  proteins  any  share  whatever  in  (he  energy 
which  appears  as  muscular  contraction.  The  proteins,  they  said, 
'  repair  the  slow  waste  of  the  framework  of  the  muscular  machine, 
replace  a  loose  rivet,  a  worn-out  belt,  as  occasion  may  require ;  the 


6oo  METABOLISM.  NUTRITION  AND  DIETETICS 

carbo-hydrates  and  fats  are  the  fuel  which  feeds  the  furnaces  of  life, 
the  material  which,  dead  itself,  is  oxidized  in  the  interstices  of  the 
living  substance,  and  yields  the  energy  for  its  work.' 

Now,  it  is  a  singular  coincidence,  and  full  of  instruction  for  the 
ingenuous  student  of  science,  that  the  facts  which  were  supposed 
absolutely  to  disprove  the  older  theory,  and  absolutely  to  establish  its 
more  modem  rival,  are  now  seen  to  do  neither  the  one  thing  nor  the 
other.  The  fact — and  it  is  a  fact — that  the  excretion  of  nitrogen  is 
but  little  affected  by  muscular  contraction,  does  not  prove  that  none 
of  the  energy  of  muscular  work  comes  from  proteins;  the  fact  that, 
under  certain  conditions,  some  of  the  muscular  energy  must  apparently 
come  from  non-nitrogenous  materials,  does  not  prove  that  these  are  the 
normal  source  of  it  all.  The  distinction  had  again  been  made  too 
absolute.  The  pendulum  must  again  swing  back  a  little;  and  the 
experiments  of  Pfiiiger  and  his  pupils  were  soon  to  set  it  moving. 

In  the  first  place,  it  is  not  perfectly  correct  to  say  that  work 
causes  no  increase  in  the  excretion  of  nitrogen;  excessive  work  in 
man,  and  work,  severe  but  not  excessive,  in  a  flesh-fed  dog  (Pfiiiger), 
do  cause  somewhat  more  nitrogen  to  be  given  off.  On  the  first  day 
of  work  the  increase  is  always  much  less  than  on  the  second  and  th'rd ; 
and  on  the  first  and  second  rest  days,  following  work,  the  ehmina- 
tion  of  nitrogen  is  still  increased.  After  excessive  exercise  in  man 
not  only  is  the  urea  increased,  but  also  the  ammonia,  kreatinin,  and 
if  the  subject  is  in  poor  training,  the  uric  acid  and  purin  bases  (Pat on. 
Stockman,  etc.).  Moderate  exercise  causes  no  increase  on  the  first 
day,  but  a  slight  increase  on  the  second.  The  meaning  of  these 
facts  seems  to  be  that  during  muscular  work  the  intensity  of  which 
does  not  exceed  certain  limits,  the  protein  waste  of  the  muscular 
substance  itself  is  no  greater  than  during  rest.  When,  however,  the 
machine  is  '  speeded  up  '  beyond  a  certain  point  the  wear  and  tear 
is  sensibly  increased  and  an  excess  of  tissue-protein  is  katabolized. 
There  is  no  reason  to  suppose  that  the  tissue-protein  thus  broken 
down  will  not  yield  energy  for  the  muscular  work  by  the  oxidation 
of  its  non-nitrogenous  residue,  just  as  well  as  the  surplus  amino- 
bodies  derived  from  food-protein.  The  muscular  machine  has  the 
peculiarity  that  it  is  constructed  of  combustible  material;  even  the 
dust  and  the  splinters,  if  we  may  so  express  it,  which  represent  the 
wear  and  tear  of  the  machine  can  be  burnt  in  the  furnace  which  keeps 
it  going. 

In  the  second  place,  even  if  the  excretion  of  nitrogen  were  entirely 
unaffected  by  work,  this  would  not  prove  that  none  of  the 
energy  of  the  work  comes  from  proteins.  For,  as  we  have  seen, 
it  is  after  the  nitrogen  has  been  split  off  and  converted  into  urea 
that  the  energy  of  a  great  part  of  the  food-protein  is  developed  by 
oxidation.  Further,  since  the  animal  body  is  a  beautifully-balanced 
mechanism  which  constantly  adapts  itself  to  its  conditions,  it  is 
conceivable  that  it  may,  when  called  upon  to  labour,  save  proteins 
from  lower  uses  to  devote  them  to  muscular  contraction.     In  this 


STATISTICS  OF  NUTRITION  box 

case  the  excretion  of  nitrogen  would  not  necessarily  bt,  altered;  the 
proteins  which,  in  the  absence  of  work,  would  have  been  oxidized 
within  the  muscular  substance  or  elsewhere,  their  energy  appearing 
entirely  as  heat,  may,  wlien  the  call  for  protein  to  take  the  place  of 
that  broken  down  in  muscular  contraction  arises,  be  diverted  to  this 
purpose. 

In  any  case,  there  is  no  doubt  that  a  dog  fed  on  lean  meat  ma}' 
go  on  for  a  long  rime  performing  far  more  work  than  can  be  yielded 
by  the  energy  of  fat  and  carbo-hydrates  occurring  in  traces  in  the 
food,  or  taken  from  the  stock  in  the  animal's  body  at  the  beginning 
of  the  period  at  work.  A  large  portion,  and  perhaps  the  whole,  of 
the  work,  must  in  this  case  be  derived  from  the  energy  of  the  pro- 
teins (Pfliiger).  On  the  other  hand,  it  is  well  established  that  when 
fats  and  carbo-hydrates  are  present  in  sufficient  quantity  in  the 
tissues  or  the  food,  they  constitute  the  main  source  of  the  energy 
of  muscular  contraction  (p.  746),  and  there  is  some  evidence  that  of 
the  two  classes  of  food  materials  carbo-hydrates  in  the  form  of 
dextrose  (or  glycogen)  is  the  material  of  election. 

The  outcome,  then,  of  this  famous  controversy  is  essentially  a 
compromise.  Everybody  now  admits  that  the  muscular  machine 
can  and  does  utilize  predominantly  any  one  of  the  great  groups 
of  food  substances,  be  it  carbo-hydrate,  fat,  or  protein,  when  the 
dietetic  conditions  are  such  that  only  one  of  these  is  offered  to  it 
in  large  amount,  the  others  being  either  absent  or  offered  in  small 
amount.  To  be  sure,  amino-acids  are  not  the  first  choice,  but  if 
it  must  do  so  the  muscle  can  make  shift  with  them,  and  can  indeed 
make  them  serve  excellently  well.  When  all  the  food  substances 
are  present  in  abundance,  carbo-hydrate  is  favoured  above  fat,  and 
fat  above  protein. 

Experience  has  shown  that  the  minimum  quantity  of  nitrogen 
required  in  the  food  of  a  man  whose  daily  work  involves  hard 
physical  toil  is  higher  than  the  minimum  required  by  a  person  lead- 
ing an  easy,  sedentary  life.  This  is  evidently  in  accordance  with 
the  view  that  protein  is  actually  used  up  in  muscular  contraction ; 
but  it  is  not  inconsistent  with  the  opposite  view.  For  the  body  of  a 
man  fit  for  continuous  hard  labour  has  a  greater  mass  of  muscle 
to  feed  than  the  bodj'  of  a  man  who  is  only  fit  to  handle  a  composing- 
stick,  or  drive  a  quill,  or  ply  a  needle;  and  the  greater  the  muscular 
mass,  the  greater  the  muscular  waste.  But  if  an  animal  just  in 
nitrogenous  equilibrium  on  a  diet  of  lean  meat  when  doing  no  work 
is  made  to  labour  day  after  day,  it  will  lose  flesh  unless  the  diet 
be  increased.  This  must  mean  that  some  of  the  protein  is  being 
diverted  to  muscular  work,  and  that  the  balance  is  not  sufficient 
to  keep  up  the  original  mass  of  '  flesh  '  (see  p.  615). 

Relative  Value  of  Different  Proteins  in  Nutrition — Synthesis  of 
Amino-Acids. — ^The  fact  that  the  various  proteins  dilk-r  quantita- 


602  METABOLISM,  NUTRITION  AND  DIETETICS 

ti  vely  and  qualitatively  in  respect  to  their  amino-acids  raises  the  ques- 
tion of  the  relative  value  of  different  proteins  in  nutrition.  In  this  is 
involved  the  further  question,  whether  the  body  can  itself  sjmthesize 
from  other  materials  any  of  the  amino-acids  which  may  be  deficient, 
or  change  one  amino-acid  into  another.  That  the  '  peptones  '  derived 
from  a  protein  which  is  itself  capable  of  permanently  supplying 
the  whole  nitrogenous  intake  of  the  organism  can  be  substituted 
for  the  protein  scarcely  needs  demonstration,  since  it  is  known  that 
the  protein  is  converted  into  peptones  in  digestion.  Nevertheless, 
this  has  been  proved  conclusively  by -feeding  experiments  with 
peptones.  It  was  to  be  expected,  too,  leaving  out  of  account  all 
consideration  of  the  means  of  overcoming  the  repugnance  of  animals 
to  accepting  such  unnatural  food  substances,  that  the  further 
products  of  protein  hydrolysis,  the  amino-acids,  etc.,  could  be 
substituted  for  the  original  proteins  when  these  were  themselves 
adequate.  For  it  is  in  the  form  of  amino-acids  or  at  most  of  such 
relatively  simple  polypeptide  groups  as  may  still  hang  together 
after  complete  digestion  and  absorption,  that  the  nitrogenous  food 
substances  are  normally  offered  to  the  tissues.  Experimental 
demonstration  of  the  feasibility  of  this  substitution  has  also  been 
obtained.  The  split  products  of  meat,  for  example,  will  keep  an 
animal  in  nitrogen  equilibrium  as  well  as  the  meat  from  which  they 
are  derived.  But  what  happens  when  one  or  more  of  the  amino- 
acids  found  in  the  proteins  of  the  body  are  missing  from  the  protein 
of  the  food  ?  That  the  components  of  an  amino-acid  like  cirginin 
(ornithin  and  urea),  into  which  it  can  be  split  not  only  by  the 
possibly  crude  and  violent  methods  of  the  chemical  laboratorj^  but 
also  by  the  delicate  and  precisely-adapted  '  biological  '  action  of  a 
special  enzyme  (arginase),  should  be  able  to  replace  the  original 
amino-acid  is  a  fact  which  does  not  greatly  help  towards  an  answer. 
For  when  these  components,  or  ornithin  alone,  since  urea  is  always 
present  in  the  body,  are  given  instead  of  arginin,  the  reversal  of  the 
enzyme  reaction  by  which  arginin  is  decomposed  is  all  that  is  neces- 
sary for  its  S3mthesis,  and  the  reversal  of  such  a  reaction  is  doubtless 
a  very  commonplace  affair  in  tissue  metabolism.  The  formation 
of  one  amino-acid  from  another,  or  from  materials  which  do  not 
originate  exclusively  from  protein,  is  a  different  thing,  and  the 
answer  to  the  question  raised,  so  far  as  it  can  yet  be  given,  is  that 
the  way  in  which  the  body  deals  with  a  deficiency  in  the  protein 
'  building  stones  '  depends  upon  the  nature  of  the  missing  amino- 
acids.  Thus,  the  phospho-protein  casein  does  not  yield  glycin  on 
hydrolysis;  yet  it  has  been  shown  that  casein  is  a  perfectly  adequate 
or  complete  protein  food  capable  of  covering  the  whole  nitrogen 
requirement  of  the  body  over  long  periods.  The  same  is  true  of  the 
cleavage  products  of  casein  which  has  been  subjected  to  pancreatic 
digestion.     In  an  animal  fed  on  no  other  protein  than  casein,  with 


STATISTICS  OF  NUTRITION  603 

suitable  quantities  of  carbo-hydrate  and  fat  in  addition,  the  glycin 
contained  in  certain  of  the  body  proteins  must  therefore  have  been 
produced  in  the  body  itself.  We  have  already  seen  (p.  571)  that 
for  the  synthesis  of  hippuric  acid  after  the  administration  of  benzoic 
acid,  glycin  is  necessary,  and  the  quantity  of  hippuric  acid  which 
can  be  thus  produced  is  so  great  that  it  is  impossible  to  suppose 
that  it  all  comes  from  glycin  preformed  in  the  body  or  from  glycin 
in  the  food  substances.  It  may  accordingly  be  taken  as  pro\ed 
that  the  tissues  have  the  power  of  synthesizing  at  least  this  one  of 
the  amino-acids  (amino-acetic  acid),  reckoned  among  the  protein 
'  building  stones. '  It  is  said  that  if  the  casein  has  been  hydrolysed 
by  acid,  the  products  will  not  preserve  nitrogen  equilibrium,  per- 
haps because  the  acid  has  broken  up  all  the  polypeptides  (p.  2), 
some  of  which  the  cells  may  Reed  as  the  starting-point  of  protein 
synthesis.     This,  however,  is  uncertain. 

Lysin  also  appears  to  be  capable  of  being  synthesized  in  the  body, 
and  protein  foods  free  from  lysin,  or  containing  only  a  trace  of  it, 
may  yet  be  adequate  for  nutrition  and  growth.  Prohn,  too,  is  not 
indispensable,  and  this  is  of  special  interest,  for  the  amino-acids 
hitherto  mentioned  as  capable  of  being  built  up  in  the  tissues  are 
a.ll  more  or  less  directly  related  to  each  other,  being  derivatives  of 
the  series  of  saturated  fatty  acids.  The  task  of  changing  one  of 
these  into  another  in  which  the  food  is  deficient  may,  therefore,  be 
considered  a  comparatively  easy  one.  But  prolin  has  no  obvious 
relation  to  most  of  the  other  amino-acids. 

It  is  a-pyrrolidin  carboxylic  acid, 

CHo — CHj  Cri2 — Cxia 

i     I  I     J 

CHo     CH.COOH— ?.e.,  pyrrolidin,    CHg     CHj 

\     /  \     / 

NH  NH 

in  which  H  in  one  of  the  CHg  groups  is  replaced  by  carbnx}-!  (COOH). 
It  has  been  suggested  that  prolin  may  be  formed  in  the  body  from 
glutaminic  (amino-glutaric)  acid,  which  by  loss  of  a  molecule  of  water 
can  be  made  to  yield  a-pyrrolidon  carboxylic  acid.     Thus, 

CH2.CH2.CH.COOH  CHg— CH, 

COOH      NH,  -H2O      =     CO       CH.COOH 

\     / 

NH 

Glutaminic  acid.      -  a-pyrroliiion  carboxylic  acid. 

By  reduction  the  latter  compound  might  be  changed  into  prolin. 

With  proteins  deficient  in  certain  other  amino-acids  a  totally 
different  result  has  been  obtained.  Gelatin,  for  example,  contains 
most  of  the  amino-acids  and  other  groups  which  compose  the  body 
proteins,  but  tyxosin,  cystin,  and  tryptophane  are  lacking  in  the 


6o4  METABOLISM.  NUTRITION  AND  DIETETICS 

gelatin  molecule.  Zein,  an  alcohol-soluble  protein  or  prolamin* 
derived  from  maize,  yields  no  tryptophane,  glycin,  or  lysin.  Now, 
it  is  found  that  neither  gelatin  nor  zein  can  replace  the  whole  of 
the  ordinary  proteins  in  the  food.  When  only  enough  protein  is 
taken  to  prevent  loss  of  nitrogen  from  the  body,  one-fifth  of  the 
necessary  nitrogen  can  be  supplied  in  the  form  of  gelatin.  When 
the  food  is  much  richer  than  this  in  ordinary  protein,  a  correspond- 
ingly greater  proportion  of  the  protein  can  be  replaced  by  gelatin. 
The  surplus  is  not  used  in  the  endogenous  metabolism  of  the  cells 
(p.  56.1),  but  supplies  energy  to  the  body  after  the  elimination  of 
its  nitrogen  as  urea,  just  as  the  surplus  protein  would  do.  Thus 
gelatin  economizes  protein  in  the  same  way  that  fat  and  carbo- 
hydrates do,  but  also  to  some  extent  in  a  different  way  by  supplying 
'  building  stones  '  for  the  protoplasm.  It  is  therefore  an  interesting 
question  whether  gelatin  can  fully  replace  protein  when  the  missing 
substances  are  given  in  addition.  Kauffmann  has  stated  that  his 
own  nitrogen  requirement  (15-2  grammes)  was  almost  completely 
covered  by  a  mixture  containing  93  per  cent,  of  the  nitrogen  in  the 
form  of  gelatin,  4  per  cent,  as  tyrosin,  2  per  cent,  as  cystin,  and 
I  per  cent,  as  tryptophane,  in  addition  to  the  same  amounts  of 
carbo-hydrate  and  fatty  food  as  in  the  comparison  diet,  in  which 
the  nitrogen  was  supplied  in  the  form  of  plasmon,  a  commercial 
preparation  of  casein. 

Similar  results  have  been  reported  in  experiments  on  animals  in 
which  attempts  have  been  made  to  '  complete  '  such  inadequate 
proteins  by  addition  of  the  missing  amino-bodies,  with  fair  but, 
according  to  Osborne  and  Mendel,  not  entirely  satisfactory  results. 
The  converse  experiment,  in  which  an  amino-acid  such  as  trypto- 
phane has  been  purposely  eliminated  from  the  food  mixture,  has 
also  been  tried,  with  the  result  that  rapid  deterioration  in  the 
condition  of  the  animal  ensued.  It  would  seem,  indeed,  that 
whatever  capacity  the  animal  body  may  have  for  synthesizing 
certain  of  the  amino-acids,  this  power  does  not  extend  to  the  cychc 
compounds  tryptophane,  tyrosin,  phenylalanin,  and  histidin,  which 
must  be  supplied  in  the  food.  It  has  been  suggested  by  Osborne 
that  in  this  regard  an  essential  difference  exists  between  the  animal 
and  the  plant,  the  latter  alone  being  endowed  with  the  function  of 
'  cyclopoiesis,'  or  formation  of  substances  of  the  cyclic  type.  It 
is  not  clearly  understood  as  yet  on  what  this  difference  really  hinges, 
whether,  as  some  have  supposed,  on  the  inability  of  the  animal 
organism  to  form  the  appropriate  fatty  acid  radicals,  or  on  some 

*  The  prolamins  are  so  called  because  on  hydrolysis  they  yield  exceptionally 
large  amounts  of  prolin  (p.  354)  and  ammonia.  They  are  insoluble  in  water 
and  absolute  alcohol,  but  soluble  in  70  to  80  per  cent,  alcohol  and  in  dilute 
acids  and  alkalies.  Besides  zein  they  include  gliadin  (from  wheat  and  rye), 
hordcin  (from  barley),  and  bynin  (from  malt).  They  arc  extraordinarily  rich 
in  glutaminic  acid,  hordein  yielding  more  than  any  protein  hitherto  investi- 
gated (over  41  per  cent). 


STATISTICS  OF  NUTRITION  605 

other  limitation  of  its  chemical  powers.  While  the  cyclic  (and  hetero- 
cyclic) compounds  cannot  be  replaced  by  other  '  Bausteine  '  of  the 
proteins,  they  may  to  some  extent  replace  each  other.  Thus  it  would 
seem  that  tyrosin  can  be  replaced  by  phenylalanin  (Abderhalden). 
While  some  of  the  food  proteins  like  casein  are  suflScient  by 
themselves  to  supply  all  the  amino-bodies  necessary  not  only  for 
the  maintenance,  but  also  for  the  growth  of  the  body,  and  can 
accordingly  be  termed  adequate  or  complete  protein  food  sub- 
stances, others,  hke  gelatin,  are  insufficient  by  themselves  to  supply 
the  protein  required  for  mere  maintenance,  still  less  for  growth, 
and  may  be  spoken  of  as  inadequate  or  incomplete  proteins.  There 
is  a  third  intermediate  group,  comprising  proteins  which  suffice 
when  given  as  the  sole  protein  food  to  maintain  the  body  for  an 
indefinitely  long  period,  and  to  repair  the  tissue  waste  without  per- 
mitting growth  of  the  animal  to  take  place.  Gliadin  and  hordein  1 
.(see  footnote,  p.  604)  are  representatives  of  this  group.  The  ex- 
periments of  Osborne  and  Mendel  with  gliadin  are  of  special  interest, 
since  this  substance  is  very  differently  constituted  from  the  ordinary' 
food  proteins,  as  well  as  from  the  tissue  proteins  of  the  animal 
body.  While,  as  already  stated,  it  yields  very  large  quantities  of 
glutaminic  acid,  prolin,  and  ammonia,  it  either  contains  no  lysin 
and  no  glycin,  or  yields  too  little  to  be  detected  with  certainty. 
It  also  yields  comparatively  little  histidin  and  arginin.  Now,  it 
has  been  foimd  that  a  dietary  containing  carbo-hydrate,  fats,  and 
inorganic  salts,  but  no  protein  except  gliadin,  suffices  to  maintain 
adult  rats  in  good  condition  for  very  long  periods  (up  to  290  days), 
and  also  to  maintain  young  rats  in  a  stationary  condition  as  regards 
growth,  but  in  perfect  health.  The  youthful  appearance  of  the  rats 
whose  growth  was  thus  inhibited  was  very  striking,  and  corresponded 
with  their  size  rather  than  with  their  age.  The  capacity  for  growth 
on  a  normal  diet  was  apparently  not  in  the  least  diminished ;  the 
growth  processes  simply  remained  in  abeyance. 

'  In  one  rat,  after  a  continuous  suppression  of  growth  lasting  277  days, 
when  the  animal  was  314  days  old — an  age  at  which  normally  little  or 
no  growth  takes  place — satisfactory  growth  was  resumed  on  a  suitable 
diet.'  A  still  more  remarkable  experiment  was  the  following:  '  A  male 
rat,  kept  for  154  days  with  gliadin  as  the  sole  protein  in  the  food,  was 
paired  with  a  female  also  on  the  gliadin  diet.  At  the  end  of  178  days 
on  the  gliadin  diet  she  gave  birth  to  four  young,  which  were  satisfactorily 
nourished  by  the  mother,  still  on  gliadin,  during  the  first  month  of 
their  existence.  After  a  month  three  of  the  young  rats  were  removed 
from  the  mother  and  put  on  diets  of  casein  food  {i.e.,  casein  plus  suitable 
proportions  of  carbo-hydrate,  fat,  and  inorganic  materials),  edeotin 
food  and  milk  food  respectively.  The  fourth  was  left  with  the  mother. 
The  fourth  rat  began  to  evince  a  failure  to  grow  at  about  the  period 
(thirty  days)  when  young  rats  are  wont  to  depend  upon  extraneous  food. 

The  meaning  of  this  last  observation  can  only  be  that  the  young 
animal,  when  obliged  to  depend  upon  its  share  of  the  gliadin  food 


6o6  METABOLISM,  NUTRITION  AND  DIETETICS 

left  with  the  mother  in  place  of  the  milk  formed  by  the  mother 
from  this  same  gliadin  food  mixture,  showed  the  typical  failure  to 
grow  on  a  diet  inadequate  as  regards  the  power  of  producing  growth 
in  respect  to  the  protein  contained  in  it.  On  the  other  hand,  in  the 
body  of  the  mother  this  inadequate  diet  had  been  so  transformed 
that  not  only  had  she  maintained  her  body-weight  and  repaired 
her  tissue  waste  completely,  but  she  had  produced  from  it  every- 
thing necessary  for  the  development  of  the  embryo  rats  up  to  full 
term,  and  after  that  ever3rthing  necessary  (in  the  form  of  milk) 
for  their  normal  growth  during  the  period  of  suckling.  On  the 
whole,  a  very  large  amount  of  body  tissue  in  proportion  to  the 
original  weight  of  the  mother  must  have  been  formed  or  renewed 
in  the  200  days  or  more  during  which  the  experiment  continued, 
and  during  which  gliadin  was  being  steadily  transmuted  into  tissue 
protein,  and  latterly  into  the  proteins  of  milk  as  well,  by  what 
might  almost  be  called  a  feat  of  chemical  legerdemain.  There  must 
have  occurred  a  synthesis  '  not  only  of  the  Bausteine  (the  "  building- 
stones  ")  deficient  in  the  protein  intake,  but  likewise  of  tissue  and 
milk  components  like  the  nucleic  acids  (with  their  content  of  purins, 
pyrimidins,  and  organically  combined  phosphorus)  and  phospho 
proteins  like  casein,  etc.,  which  were  completely  missing  '  in  the  food. 

It  has  been  suggested  that  the  bacteria  of  the  alimentary  canal, 
which,  of  course,  are  plant  cells,  may  have  and  may  exercise  on  a  large 
scale  the  power  of  building  up  new  amino-acids  from  a  variety  of 
materials  in  the  intestinal  contents,  and  that  they  may  thus  be  synthe- 
sizing agents,  thanks  to  which  inadequate  proteins  may  be  reshaped  to 
proteins  adequate  to  the  needs  of  the  body.  It  is  precisely,  however, 
in  the  case  of  incomplete  proteins  like  gelatin  deficient  in  cyclical 
compounds,  that  the  body  fails  to  effect  the  necessary  transformation 
in  spite  of  the  fact  that  plant  cells  are  supposed  to  be  specially  capable 
of  forming  these  compounds.  In  any  case  bacterial  action  would  not 
explain  why  proteins  like  gliadin  and  hordein  are  only  adequate  for  the 
renewal  of  tissue,  and  not  for  its  growth.  This  points  rather  to  the 
possibility  that  the  processes  by  which  the  nitrogenous  compounds 
degraded  in  cellular  metabolism  are  replaced  are  not  of  the  same  char- 
acter as  the  processes  by  which  new  nitrogenous  complexes  are  built 
up  into  growing  protoplasm.  If,  for  instance,  the  protein  molecule  is 
not  completely  disrupted  in  ordinary  metabolism,  it  will  not  need  to  be 
completely  reconstructed,  while  in  the  formation  of  new  tissue  complete 
protein  molecules  will  have  to  be  synthesized.  Incomplete  proteins 
like  gliadin  may  furnish  building-stones  adequate  for  repairing  the 
house,  but  inadequate  for  building  it  from  the  foundations. 

Income  and  Expenditure  of  Carbon — ^The  Carbon  Balance-Sheet. — 
This  division  of  the  subject  has  been  necessarily  referred  to  in 
treating  of  the  nitrogen  balance-sheet,  and  may  now  be  formally 
completed. 

Carbon  Equilibrium. — A  body  in  nitrogenous  equilibrium  may  or 
may  not  be  in  carbon  equilibrium.  It  has  been  repeatedly  pointed 
out  that  the  continued  loss  or  gain  of  carbon  by  an  organism  in 


STATISTICS  OF  NUTRITION  607 

nitrogenous  equilibrium  means  the  loss  or  gain  of  fat;  and,  since 
the  quantity  of  fat  in  the  body  may  vary  within  wide  limits  without 
harm,  carbon  equilibrium  is  less  important  than  nitrogen  equili- 
brium. It  is  also  less  easily  attained  when  the  carbon  of  the  food 
is  increased,  for  the  consumption  of  fat  is  not  necessarily  increased 
with  the  supply  of  fat  or  fat-producing  food,  and  there  is  by  no 
means  the  same  prompt  adjustment  of  expenditure  to  income  in 
the  case  of  carbon  as  in  the  case  of  nitrogen. 

Carbon  equilibrium  can  be  obtained  in  a  flesh-eating  animal,  Hke 
a  dog,  with  an  exclusively  protein  diet;  but  a  far  higher  minimum 
is  required  than  for  nitrogenous  equilibrium  alone.  Voit's  dog 
required  at  least  1,500  grammes  of  meat  in  the  twenty-four  hours 
to  prevent  his  body  from  losing  carbon.  For  a  man  weighing 
70  kilos,  the  daily  excretion  of  carbon  on  an  ordinary  diet  is  250  to 
300  grammes.  About  2,000  grammes  of  lean  meat  would  be  re- 
quired to  yield  this  quantity  of  carbon;  and,  even  if  such  a  mass 
could  be  digested  and  absorbed,  more  than  three  times  the  necessary 
nitrogen  would  have  to  undergo  preliminary  cleavage  and  excretion 
as  urea  or  be  thrown  upon  the  tissues. 

Not  only  may  carbon  equilibrium  be  maintained  for  a  short  time 
in  a  dog  on  a  diet  containing  fat  only,  or  fat  and  carbo-hydrates,  but 
the  expenditure  of  carbon  may  be  less  than  the  income,  and  fat  may 
be  stored  up.  But,  of  course,  if  this  diet  is  continued,  the  animal 
ultimately  dies  of  nitrogen  starvation. 

So  far  we  have  spoken  only  of  the  income  and  expenditure  of 
carbon  and  nitrogen;  and  from  these  data  alone  it  is  possible  to 
deduce  many  important  facts  in  metabolism,  since,  knowing  the 
elementary  composition  of  proteins,  fats,  and  carbo-hydrates,  we 
can,  on  certain  assumptions,  translate  into  terms  of  proteins  or  fat 
the  gain  or  loss  of  an  organism  in  nitrogen  and  carbon,  or  in  carbon 
alone.  But  the  hydrogen  and  oxygen  contained  in  the  solids  and 
water  of  the  food,  and  the  oxygen  taken  in  by  the  lungs,  are  just  as 
important  as  the  carbon  and  nitrogen ;  it  is  just  as  necessary  to  take 
account  of  them  in  drawing  up  a  complete  and  accurate  balance- 
sheet  of  nutrition.  Fortunately,  however,  it  is  permissible  to 
devote  much  less  time  to  them  here,  for  when  we  have  determined 
the  quantitative  relations  of  the  absorption  and  excretion  of  the 
carbon  and  nitrogen,  we  have  also  to  a  large  extent  determined 
those  of  the  oxygen  and  hydrogen. 

Income  and  Expenditure  of  Oxygen  and  Hydrogen. — The  oxj'gen 
absorbed  as  gas  and  in  the  solids  of  the  food  is  given  off  chiefly  as 
carbon  dioxide  by  the  lungs;  to  a  small  extent  as  water  by  the  lungs, 
kidneys,  and  skin;  and  as  urea  and  other  substances  irt  the  urine 
and  fseces.  The  hydrogen  of  the  solids  of  the  food  is  excreted  in 
part  as  urea,  but  in  far  larger  amount  as  water.  The  hydrogen  and 
oxygen  of  the  ingested  water  pass  off  as  water,  without,  so  far  as 


6o8  METABOLISM.  NUTRITION  AND  DIETETICS 

we  know,  undergoing  any  chemical  change,  or  existing  in  any  othei 
form  within  the  body.  But  it  is  important  to  recognize  that 
although  none  of  the  water  taken  in  as  such  is  broken  up,  some 
water  is  manufactured  in  the  tissues  by  the  oxidation  of  hydrogen. 
We  have  already  considered  (p.  240)  the  gaseous  exchange  in  the 
lungs,  and  we  have  seen  that  all  the  oxygen  taken  in  does  not 
reappear  as  carbon  dioxide.  It  was  stated  there  that  the  missing 
oxygen  goes  to  oxidize  other  elements  than  carbon,  and  especially 
to  oxidize  hydrogen.  We  have  now  to  explain  more  fully  the  cause 
of  this  oxygen  deficit 

The  Oxygen  Deficit.— The  carbo-hydrates  contain  in  themselves 
enough  oxygen  to  form  water  with  all  their  hydrogen ;  they  account  for 
a  part  of  the  water-formation  in  the  body,  but  for  none  of  the  oxygen 
deficit. 

The  fats  are  very  different ;  their  hydrogen  can  be  nothing  like  com- 
pletely oxidized  by  their  oxygen.  A  gramme  of  hydrogen  is  contained 
in  8*5  grammes  of  dry  fat,  and  needs  8  grammes  of  oxygen  for  its  com- 
plete combustion.  Only  i  gramme  of  oxygen  is  yielded  by  the  fat 
itself;  so  that  if  a  man  uses  100  grammes  of  fat  in  twenty-four  hours, 
rather  more  than  80  grammes  of  the  oxygen  taken  in  must  go  to 
oxidize  the  hydrogen  of  the  fat. 

The  proteins  also  contribute  to  the  deficit.  In  100  grammes  of 
dry  proteins  there  arc  15  grammes  of  nitrogen,  7  grammes  of  hydrogen, 
and  21  grammes  of  oxygen.  The  carbon  does  not  concern  us  at  present. 
The  33  grammes  of  urea,  corresponding  to  100  grammes  of  protein, 
contains  15  grammes  of  nitrogen,  a  little  more  than  2  grammes  of 
hydrogen,  and  a  little  less  than  g  grammes  of  oxygen.  There  remain 
5  grammes  of  hydrogen  and  12  grammes  of  oxygen.  But  5  grammes  of 
hydrogen  needs  for  complete  combustion  40  grammes  of  oxygen ;  there- 
fore 28  grammes  of  the  oxygen  taken  in  must  go  to  oxidize  the  hydrogen 
of  100  grammes  of  protein.  Taking  140  grammes  of  protein  as  the 
amount  in  a  liberal  diet  for  a  man,  we  get  39  grammes  as  the  required 
quantity  of  oxygen.  This,  added  to  the  80  grammes  needed  for  the 
hydrogen  of  the  fat,  makes  a  total  of,  say,  120  grammes,  equivalent  to 
about  85  litres  of  oxygen.  A  small  amount  of  oxygen  also  goes  to 
oxidize  the  sulphur  of  proteins. 

With  a  diet  containing  less  fat  and  protein  and  more  carbo-hydrate, 
the  oxygen  deficit  would  of  course  be  less. 

The  Production  of  Water  in  the  Body. — One  gramme  of  hydrogen 
corresponds  to  9  grammes  of  water.  In  140  grammes  of  proteins  and 
100  grammes  of  fat  there  are,  in  round  numbers,  22  grammes  of  hydro- 
gen; in  350  grammes  of  starch,  2i'5  grammes.  With  this  diet, 
43*5  grammes  of  hydrogen  is  oxidized  to  water  within  the  body  in 
twenty-four  hours,  corresponding  to  a  water  production  of  391  grammes, 
or  15  to  20  per  cent,  of  the  whole  excretion  of  water.  It  has  been 
observed  that  during  starvation  the  tissues  sometimes  become  richer 
in  water,  even  when  none  is  drunk.  The  only  explanation  is  that  the 
elimination  of  water  does  not  keep  pace  with  the  rate  at  which  it  is 
produced  from  the  hydrogen  of  the  broken-down  tissue -substances,  or 
set  free  from  the  solids  with  which  it  is  (physically  ?)  united. 

Inorganic  Salts. — The  inorganic  salts  of  the  excreta,  like  the 
water,  are  for  the  most  part  derived  from  the  salts  of  the  food, 


STATISTICS  OF  NUTRITION  609 

which  do  not  in  general  undergo  decomposition  in  the  body.  A 
portion  of  the  chlorides,  however,  is  broken  up  to  yield  the  hydro- 
chloric acid  of  the  gastric  juice.  Within  the  body  sonic  of  the  salts 
are  more  or  less  intimately  united  to  the  proteins  of  the  tissues  and 
juices,  some  simply  dissolved  in  the  latter.  The  chlorides,  phos- 
phates and  carbonates  are  the  most  important;  the  potassium  salts 
belong  especially  to  the  organized  tissue  elements,  the  sodium  salts 
to  the  liquids  of  the  body;  calcium  phosphate  and  carbonate  pre- 
dominate in  the  bones.  The  amount  and  composition  of  the  ash 
of  each  organ  only  change  within  narrow  limits.  In  hunger  the 
organism  clings  to  its  inorganic  materials,  as  it  clings  to  its  tissue- 
proteins;  the  former  are  just  as  essential  to  life  as  the  latter.  In  a 
starving  animal  chlorine  almost  disappears  from  the  urine  at  a  time 
when  there  is  still  much  chlorine  in  the  bod}'^;  only  the  inorganic 
salts  which  have  been  united  to  the  used-up  proteins  are  excreted, 
so  that  a  starving  animal  never  dies  for  want  of  salts. 

When  sodium  chloride  is  omitted  as  an  addition  to  the  food  of 
man,  the  decomposition  of  protein  seems  to  be  slightly  accelerated, 
but  for  a  time,  at  least,  there  are  no  serious  symptoms  (Belli). 

It  is  a  general  rule  that  purely  carnivorous  animals  do  not  desire 
salt,  and  the  same  is  true  of  human  beings  living  on  a  purely  animal 
diet,  while  vegetable  feeders  eagerly  seek  it.  On  the  other  hand, 
when  an  animal,  even  a  carnivore,  is  fed  with  a  diet  as  far  as  possible 
artificially  freed  from  salts,  but  otherwise  sufficient,  it  dies  of  sali- 
hunger.  The  blood  first  loses  inorganic  material,  then  the  organs. 
The  total  loss  is  very  small  in  proportion  to  the  quantity  still 
retained  in  the  body;  but  it  is  sufficient  to  cause  the  death  of  a 
pigeon  in  three  weeks,  and  of  a  dog  in  six,  with  marked  symptoms 
of  muscular  and  nervous  weakness.  A  deficiency  of  lime  salts 
causes  changes  particularly  in  the  skeleton,  although  the  nutrition 
of  the  rest  of  the  body  is  also  interfered  with.  These  chrmges  are 
of  course  most  marked  in  young  animals,  in  which  the  bones  are 
growing  rapidly.  In  pigeons  on  a  diet  containing  very  little  calcium 
the  bones  of  the  skull  and  sternum  become  extremely  thin  and 
riddled  with  holes,  while  the  bones  concerned  in  movement  scarcely 
suffer  at  aU  (E.  Voit). 

It  is  not  indifferent  in  what  form  the  calcium  is  taken,  nor  can  it  be 
replaced  to  any  great  extent  by  other  earthy  bases,  as  magnesium  or 
strontium.  Weiske  fed  five  young  rabbits  of  the  same  litter  on  oats, 
a  food  relatively  poor  in  calcium.  One  of  the  rabbits  received  in 
addition  calcium  carbonate,  another  calcium  sulphate,  a  third  mag- 
nesium carbonate,  and  a  fourth  strontium  carbonate.  At  the  end  of  a 
certain  time  it  was  found  that  the  skeleton  of  the  rabbit  fed  with  calcium 
carbonate  was  the  heaviest  and  strongest  of  all,  and  contained  the 
greatest  proportion  of  mineral  matter.  Then  came  the  rabbit  fed  with 
calcium  sulphate.  The  animal  which  received  only  oats  had  the  worst- 
developed  skeleton ;  the  condition  of  the  animals  fed  with  magnesium 
and  strontium  carbonates  was  but  little  better. 

39 


6io  METABOLISM,  NUTRITION  AND  DIETETICS 

Milk  as  a  Food. — Milk  is  a  food  rich  in  calcium  and  also  in  phos 
phorus,  a  circumstance  evidently  related  to  the  rapid  development 
of  the  skeleton  in  the  young  child.  As  in  the  other  natural  foods, 
the  calcium  and  phosphorus  are  partly  in  the  form  of  organic  com- 
pounds, united  with  the  proteins,  the  calcium  especially  with 
caseinogen,  and  partly  in  the  form  of  inorganic  salts.  Both  of  these 
elements  are  more  easily  assimilated  by  the  body  in  the  organic 
than  in  the  inorganic  form.  The  same  is  true  of  iron,  which  exists 
in  organic  combination  in  the  bran  of  wheat,  in  the  haemoglobin  of 
the  blood  and  of  muscular  fibres,  in  the  nuclei  of  most  cells,  vegetable 
and  animal,  and  conspicuously  in  the  nuclein  compounds  of  the  yolk 
of  the  egg.  Attempts  have  been  made  to  increase  the  amount  of 
iron  in  hen's  eggs  by  giving  them  food  mixed  with  preparations  of 
iron — e.g.,  iron  citrate.  An  increase  takes  place,  but  only  after  a 
long  time.  Thus  in  one  experiment  loo  grammes  of  egg-substance 
contained  44  milligrammes  of  Fe203  before  the  administration  of 
the  iron  was  begun;  after  feeding  with  iron  for  three  and  a  half 
weeks  the  amount  was  4-5  milHgrammes,  after  more  than  two 
months  74  milligrammes;  and  after  a  year  only  73  milligrammes. 
Although,  as  we  have  seen,  inorganic  iron  can  be  absorbed,  it  is 
certainly  the  case  that  under  ordinary  conditions  all  the  iron  that 
the  body  receives  or  needs  is  taken  in  the  form  of  organic  com- 
pounds, since  there  is  no  inorganic  iron  in  the  natural  food  sub- 
stances. Stockman,  from  careful  estimations  of  the  quantity  of  iron 
in  a  number  of  actual  dietaries,  finds  that  it  only  amounts  to  about 
8  to  10  milligrammes  a  day.  He  concludes  that  the  greater  part  of 
it  must  be  retained  in  the  body  and  used  over  and  over  again. 

Milk  is  poor  in  iron,  but  this  does  not  hinder  the  development  of 
the  young  child,  except  when  it  is  weaned  too  late,  when  it  is  apt  to 
become  anaemic  unless  the  milk  is  supplemented  with  a  food  rich 
in  iron,  such  as  yolk  of  egg.  The  explanation  is  that  the  foetus, 
especially  in  the  last  three  months  of  intra-uterine  life,  accumulates 
a  store  of  iron  in  the  liver  and  other  organs;  so  that,  in  proportion 
to  its  body-weight,  it  is  at  birth  several  times  richer  in  iron  than  the 
adult.  This  iron,  of  course,  all  comes  from  the  mother,  and  the 
loss  is  not  exactly  balanced  by  the  excess  of  iron  in  her  food;  certain 
of  her  organs,  the  spleen,  for  instance,  though  not  apparently  the 
liver,  are  impoverished  as  regards  their  content  of  iron. 

SFXTiON  V. — Dietetics. 

There  are  two  ways  in  which  we  can  arrive  at  a  knowledge  of  the 
amount  of  the  various  food  substances  necessary  for  an  average 
man :  (a)  By  considering  the  diet  of  large  numbers  of  people  doing 
fairly  definite  work,  and  sufficiently,  but  not  extravagantly,  fed — 
e.g.,  soldiers,  gangs  of  navvies,  or  plantation  labourers;  {b)  by  making 
special  experiments  on  one  or  more  individuals. 


DIETETICS  6n 

Voit,  bringing  together  a  large  number  of  observations,  concluded 
that  an  '  average  workman,'  weighing  70  to  75  kilos,  and  working 
ten  hours  a  day,  required  in  the  twenty-four  hours  118  grammes 
protein,  56  grammes  fat,  and  500  grammes  carl)o-hydrate,  corre- 
sponding to  about  18  8  grammes*  nitrogen,  and  at  least  328  grammes 
carbon. 

Ranke  found  the  following  a  sufficient  diet  for  himself,  with  a 
body- weight  of  74  kilos : 

Proteins  -         -         -         -         -         -     100  grammes. 

Fat  .--_.«     100 

Carbo-hydrates         _        .         .         .     240 

This  corresponds  to  only  16  grammes  nitrogen  and,  say,  230  grammes 
carbon. 
A  German  soldier  in  the  held  receives  on  the  average: 

Proteins  -         -         -         -         -         -151  grammes. 

Fat  -        -         -         -        -         -      46 

Carbo-hydrates         -         -        -        -     522         ,, 

representing  about  24  grammes  nitrogen  and  340  grammes  carbon. 
The  average  ration  for  four  British  regiments  in  peace-time  con- 
tained 133  grammes  protein,  115  grammes  fat,  and  424  grammes 
carbo-hydrate  (  =  3,400  calories).  But  in  addition  the  soldiers 
constantly  obtained  at  their  own  expense  a  supper,  generally  com- 
prising meat  (Pembrey).  The  Russian  army  v/ar  ration  in  the 
Manchurian  campaign  is  said  to  have  comprised  187  grammes 
protein  and  775  grammes  carbo-hydrate,  but  only  27  gi'ammes  fat 
(  =  4,900  calories).  The  diet  of  certain  miners  (Steinheil)  and  lum- 
berers (Liebig)  contained  respectively  133  and  112  grammes  protein, 
113  and  309  grammes  fat,  and  634  and  691  grammes  carbo-hydrates. 
The  diet  of  a  Japanese  jinricksha  man  with  a  body-weight  of 
62  kilos  contained  158  grammes  protein,  and  its  total  heat  value 
was  5,050  calories.  The  work  of  these  men  in  running  long  dis- 
tances with  passengers  is  very  laborious.  They  consume  large 
amounts  of  fish,  eggs,  beef,  and  pork  during  their  periods  of  rest, 
and  large  quantities  of  rice  during  their  working  periods  (McCay). 
The  diet  of  prize-fighters  and  of  athletes  in  training  is  richer  in 
protein  than  any  of  these.  The  members  of  two  college  football 
teams  are  stated  to  have  consumed  on  the  average  225  grammes 
protein,  334  grammes  fat,  and  633  grammes  carbo-hydrates 
(  =  6,800  calories).  Caspari,  from  a  study  of  the  phenomena  of 
training,  concluded  that  continuous  bodily  work  at  a  rate  above 
the  ordinary  requires  a  large  amount  of  protein  (2  to  3  grammes  a 
day  per  kilo  of  body-weight).  But  there  seems  to  be  a  considerable 
difierence  between  different  individuals.  So  that  a  definite  and 
typical  diet  for  severe  labour  does  not  exist.  And  although  perhaps 
the  hardest  physical  work  ever  done'in  the  world  is  to  break  athletic 

*  Taking  the  percentage  of  nitrogen  ia  protein  at  16. 


612  METABOLISM,  NUTRITION  AND  DIETETICS 

records,  to  cut  and  handle  timber,  to  mine~coal,  and  to  make  war, 
the  diet  on  which  these  things  are  accomplished  is  very  variable. 

Recent  observations  tend  to  reduce  the  amount  of  protein  con- 
sidered necessary  for  a  person  under  ordinary  conditions.  Siven 
remained  in  nitrogen  equilibrium,  for  a  time  at  least,  with  an  intake 
of  only  0-07  to  o-o8  gramme  of  nitrogen  (0-4  to  0-5  gramme  of 
protein)  per  kilo  of  body-weight,  or  not  much  more  than  one-third 
of  the  amount  in  Ranke's  diet.  It  is  obvious  that  the  endogenous 
protein  Katabolism  sets  the  limit  below  which  it  must  be  impossible 
permanently  to  reduce  the  allowance  of  protein.  But  it  would  be 
very  hazardous  to  assume  that  this  theoretical  minimum  limit 
corresponds  with  the  permissible  physiological  limit.  From  ex- 
periments on  men  of  various  callings  extending  over  many  months, 
Chittenden  has  concluded  that  the  average  man  eats  at  least  twice 
as  much  protein  as  he  really  requires.  We  have  already  seen  that 
the  amount  of  nitrogen  required  to  repair  the  actual  waste  of  the 
tissues  is  comparatively  small,  and  that  with  the  ordinary  amount 
of  protein  in  the  food  a  very  large  fraction  of  the  total  nitrogen  is 
rapidly  excreted  as  urea.  There  is  no  doubt,  also,  that  many 
persons  consume  too  much  protein,  at  any  rate  in  the  form  of 
animal  food,  and  would  feel  better,  work  better,  and  probably  live 
longer,  if  they  restricted  themselves  in  this  regard.  But  there  is 
no  evidence  that  the  digestion  of  such  quantities  of  protein  as  the 
average  healthy  man  eats,  or  the  elaboration  and  excretion  of  the 
corresponding  amounts  of  urea,  '  strain  '  in  the  least  the  digestive 
apparatus,  the  liver,  or  the  kidneys.  And  it  may  just  as  well  be 
argued  that  it  is  advantageous  that  much  more  than  the  minimum 
protein  requirement  should  be  offered  to  the  tissues,  so  that  the 
appropriate  amino-acids,  even  the  scarcest  of  them,  may  be  sure 
to  be  present  in  sufficient  amount,  rather  than  that  the  organs 
should  be  subjected  to  the  unnecessary  '  strain  '  of  reconstructing 
some  of  the  amino-acids  themselves,  supposing  that  they  possess 
this  power.  In  a  question  of  this  sort  the  immemorial  experience 
and  instinct  of  mankind  cannot  be  lightly  waved  aside. 

McCay  points  out  that  while  Bengalis  in  Lower  Bengal  subsist  on 
food  containing  only  about  one-third  the  amount  of  protein  in  such 
a  '  standard  '  diet  as  Voit's  (6  to  7  grammes  of  nitrogen  a  day),  and 
may  therefore  be  supposed  to  be  immune  from  the  dangers  of  an 
excessive  protein  metabolism,  the  large  intake  of  carbo-hydrate 
rendered  necessary  by  the  poverty  of  the  food  in  protein  is  associated 
with  perhaps  g  reater  evils,  among  them  a  marked  predisposition  to 
diabetes  and  renal  troubles.  Their  weight,  chest  measurement,  and 
muscular  development  are  inferior  to  those  of  other  Asiatics  living 
in  the  same  climate,  but  with  dietetic  habits  or  economic  conditions 
which  ensure  them  a  larger  supply  of  protein.  Thus  the  natives  of 
Behar,  with  a  larger  intake  of  nitrogen,  derived  from  wheat,  and  the 
natives  of  Eastern  Bengal  with  a  larger  intake  of  nitrogen,  derived 


DIETETICS  613 

from  wheat  and  fish,  are  physically  much  superior  to  the  rice-eating 
Bengalis  of  Lower  Bengal,  although  all  belong  to  the  same  race. 

If  we  decide  the  matter  merely  on  physiological  grounds,  we  may 
say  that  for  a  man  of  70  kilos,  doing  fairly  hard,  but  not  excessive, 
work,  15  grammes  nitrogen  and  250  grammes  carbon  are  a  sufficient 
allowance.  The  15  grammes  nitrogen  will  be  contained  in  95 
grammes  dry  protein,  which  \\dll  also  yield  50  grammes  of  the 
required  carbon.  The  balance  of  200  grammes  carbon  could 
theoretically  be  suppHed  either  in  450  grammes  starch  or  in 
260  grammes  fat.  But  it  has  been  found  by  experiment  and  by 
experience  (which  is  indeed  a  very  complex  and  proverbially  expen- 
sive form  of  experiment)  that  for  civilized  man  a  mixture  of  these 
is  necessary  for  health,  although  the  nomads  of  the  Asian  steppes, 
and  the  herdsmen  of  the  Pampas,  are  said  to  subsist  for  long  periods 
on  flesh  alone,  and  a  dog  can  live  very  well  on  proteins*  and  fat. 
The  proportion  of  fat  and  carbo-hydrates  in  a  diet  may,  however, 
be  varied  within  wide  limits.  Probably  no  '  work  '  diet  should 
contain  much  less  than  40  grammes  of  fat,  but  twice  this  amount 
would  be  better;  80  grammes  fat  give  about  60  grammes  carbon, 
so  that  from  proteins  and  fat  we  have  now  got  no  grammes  of  the 
necessary  250,  leaving  140  grammes  carbon  to  be  taken  in  about 
310  grammes  starch,  or  an  equivalent  amount  of  cane-sugar  or 
dextrose.  Adding  30  grammes  inorganic  salts,  we  can  put  down  as 
the  solid  portion  of  a  normal  diet  sufficient  from  the  physiological 
point  of  view  for  a  man  of  70  kilos: 

95  grammes  proteins    -        -    =j^  of  body- weight. 

80  ,,  fat       -  -  -         =y^ 

310         ,,        carbo-hydrates     =2^5  ,, 

30         ,,        salts. 

525         „        solid  food  -    =1^5 

Now,  knowing  the  composition  of  the  various  food-stuffs,  we  can 
easily  construct  a  diet  containing  the  proper  quantities  of  nitrogen 
and  carbon,  by  using  a  table  such  as  appears  on  p.  614. 

Economic  and  social  influences — prices  and  habits — and  not 
purely  physiological  rules,  fix  the  diet  of  populations.  The  Chinese 
labourer  in  a  rice  district,  for  example,  is  apt  to  live  on  a  diet  which 
no  physiologist  would  commend.  In  order  to  obtain  15  grammes 
nitrogen  or  95  grammes  protein,  he  must  consume  more  than 
1,500  grammes  rice,  which  will  yield  700  grammes  carbon,  or  twice 
as  much  as  is  required.  But  if  many  of  the  Chinese  labourers  could 
not  live  on  rice,  or  often  on  grains  cheaper  than  rice,  they  could  not 
live  at  all.  The  Irish  peasant,  in  the  days  when  the  potato  was  his 
staple,  was  even  in  worse  case;  he  would  have  been  obliged  to 
consume  nearly  4  kilos  of  potatoes  to  obtain  his  15  grammes  nitrogen, 
while  little  more  than  half  this  amount  would  have  furnished  the 
♦  A  little  glycogen  is,  of  course,  supplied  in  the  meat. 


6i4 


METABOLISM,  NUTRITION  AND  DIETETICS 


necessary  250  grammes  carbon.  Of  course  a  diet  consisting,  week 
in  week  out,  entirely  of  potatoes  or  rice,  would  represent  an  extreme 
case,  and  no  doubt  the  total  nitrogen  ingested  would  be  considerably 
below  the  usual  proportion.  A  certain  amount  of  the  necessary 
nitrogen  is  obtained  even  by  the  poorest  populations,  in  the  form 
of  fish,  milk,  eggs,  or  bacon.  A  man  attempting  to  live  on  flesh  alone 
would  be  well  fed  as  regards  nitrogen  with  500  grammes  of  meat, 
but  nearly  four  times  as  much  would  be  required  to  yield  250 
grammes  of  carbon.  Oatmeal  and  wheat-flour  contain  nitrogen  and 
carbon  in  nearly  the  right  proportions  (i  N:  15  C),  oatmeal  being 
rather  the  better  of  the  two  in  this  respect;  and  the  best-fed  labour- 
ing populations  of  Europe  still  live  largely  on  wheaten  bread,  while, 
one  hundred  years  ago,  the  Scotch  peasant  still  cultivated  the  soil, 
as  the  Scotch  Reviewer  the  Muses,  '  on  a  little  oatmeal.'  But 
although  bread  may,  and  does,  as  a  rule,  form  the  great  staple  of 
diet,  it  is  not  of  itself  sufficient. 


Quantity 

Quantity 

Carbo- 
hydrate 

required 

required 

Nin 

Cin 

Proteia 

Fat  in 

Water 

to  yield 

to  yield 

100 

100 

in  I03 

100 

ia  100 

IS  Grms, 

N. 

250  Grms. 

c. 

Grms. 

Grms. 

Grras. 

Grms. 

in  loo 
Grms. 

Grms. 

Cheese* 

(Gruyere)  - 

300 

640 

5 

39 

31 

31 

— 

34 

Peas  (dried) 

430 

700 

3-5 

35-7 

22 

2 

55 

15 

Lean  meat  - 

440 

i860 

3-4 

13-5 

21 

3-5 

— 

74 

Wheat- flour 

650 

625 

2-3 

39-8 

12 

2 

70 

15 

Oatmeal  -     - 

580 

620 

2-6 

40-3 

13 

5-5 

65 

15 

Eggs  -     -     - 

790 

1700 

1-9 

14-7 

II-5 

12 

— 

75 

Maize      -     - 

810 

610 

1-85 

40-9 

IO-5 

7 

65 

15 

Wheat- 

bread   -     - 

1200 

II20 

1-25 

22-4 

8 

1-5 

49 

40 

Rice  -     -     - 

1530 

685 

0-9 

36-6 

5 

I 

83 

10 

Milk  -     -     - 

2380 

3540 

0-6 

7 

4 

4 

5 

85 

Potatoes 

3750 

2380 

0.4 

IO-5 

2 

0-I5 

21 

75 

Good  butter 

lOOOO 

360 

0-I5 

69 

I 

90 

8 

It  is  necessary  to  recognize  that  habit  has  much  to  do  with  the 
quantity  as  well  as  the  quality  of  the  food  used  by  an  individual 
or  a  community.  Some  concession  may  be  made  to  custom  in 
what  is  after  all,  not  a  purely  physiological  question,  and  in  this 
country  it  is  probable  that  20  grammes  of  nitrogen  and  300  grammes 
of  carbon,  while  a  liberal  is  not  an  excessive  allowance,  although 
it  is  certain  that  a  man  can  maintain  a  normal  body-weight  and 
perform  a  normal  amount  of  work  on  considerably  less,  in  some 
cases  even  with  advantage  to  his  health. 

We  may  take  500  grammes  of  bread  and  250  grammes  of  lean 
meat  as  a  fair  quantity  for  a  man    fit    for  hard  work.     Adding 

*  A  cheese  manufactured  from  whole  milk,  curdled  before  the  cream  has 
had  ti  me  to  rise,  and  therefore  rich  in  fat. 


DIETETICS 


615 


500  grammes  milk,  75  grammes  oatmeal  (as  porridge),  30  grammes 
butter,  30  grammes  fat  (with  the  meat,  or  in  other  ways),  and 
450  grammes  potatoes,  we  get  approximately  20  grammes  nitrogen 
and  300  grammes  carbon  contained  in  135  grammes  protein,  rather 
less  than  100  grammes  fat,  and  somewhat  over  400  grammes  carbo- 
hydrates.    Thus — 


N.    !     c. 

Prot-ins. 

Fat. 

Carbo- 
hydrates. 

Salts. 

(9  02.)  250  grms.  lean  mea'L  - 
(18  oz.)  500  grms.  bread 
(1  pint)  500  grms.  milk 
(i  oz.)  30  grms.  butter 
(i  oz.)  30  grms.  fat 
(16  oz.)  450  grms.  potatocr.  - 
(3  oz.)  75  grms.  oatmeal 

8 
6 
3 

1-5 
1-7 

33 

112 

35 
20 
22 

47 
30 

55 
40 
20 

10 
10 

8-5 
7-5 
20 

27 
30 

4 

245 
25 

95 
48 

4 

6-5 
3-5 
0-5 

4-5 

2 

20'2 

299 

135 

97          413       !  21 

This  would  be  a  fair  '  hard  work  '  diet  for  a  well-nourished  labourer. 
But  the  great  elasticity  of  dietetic  formulae  is  shown  in  the  following 
tables,  which  give  the  ration  of  the  German  soldier  in  peace  and  war 
and  the  minimum  allowance  per  '  statute  adult  '  prescribed  in  the 
British  regulations  concerning  passenger-ships  from  Great  Britain 
to  America. 

Ration  of  the  German  Soldier. 


Peace. 

War. 

Bread 

750  grammes. 

Bread  -         -         - 

750  grammes. 

Meat 

150 

Biscuit 

500 

Rice    - 

50 

Meat    -         -         - 

375 

cr  barley  groats 

120 

Smoked  meat 

250 

Legumes     - 

230          ,, 

or  fat 

170 

Potatoes     -         -  I 

.500         ,, 

Rice     -         -         - 

125 

or  barley  gror.ts 

125 

Legumes 

250         .. 

Minimum  Ration  fo^ 

'  Passenger  Ships. 

Bread  or  biscuit  - 

227  gramn  es. 

Sugar  -         -         - 

65  grammes. 

Wheatcn  flour 

65 

or  treacle - 

97 

or  bread  - 

81 

Tea      - 

8 

Oatmeal 

97 

or  coffee  or  cocoa 

14 

Rice     -         -         - 

97 

Salt      - 

8 

Peas    -         .         - 

97 

Mustard 

2 

Potatoes 

130 

Pepper 

I 

Beef     - 

81 

Vinegar  or  pickles 

20  c.c. 

Pork  or  preserved 

meat 

65 

In  prisons  the  object  is  to  gi\e  the  minimum  amount  of  the  plamcst 
food  which  will  suffice  to  maintain  the  prisoners  in  liealth.  A  '  hard 
work  '  prison  diet  in  Munich  was  found  to  contain  104  grammes  proteins, 
38  grammes  fat,  and  521  gra,nmics  carbo-hydrates;  a  'no-work'  diet, 
only  87  grammes  proteins,  22  grammes  fat,  anel  305  grammes  carbo- 
hydrates. Here  wc  recognize  the  influence  of  price;  carbon  can  Ix? 
much   more   cheaply   obtained   in    vegetable    carho-liydmtcs   than   in 


6i6  METABOLISM,  NUTRITION  AND  DIETETICS 

animal  fats;  the  cheapest  possible  diet  contains  a  minimum  of  animal 
fat  and  proteins. 

Many  poor  persons  live  on  a  diet  which  would  not  maintain  a  strong 
man,  for  an  emaciated  body  has  a  smaller  mass  of  flesh  to  keep  up,  and 
therefore  needs  less  protein ;  it  can  do  little  work,  and  therefore  needs 
less  food  of  all  kinds.  A  London  needlewoman,  according  to  Playfair, 
subsists,  or  did  subsist  thirty  years  ago,  on  54  grammes  protein, 
29  grammes  fat,  and  292  grammes  carbo-hydrates.  But  this  is  the 
irreducible  minimum  of  the  deepest  poverty,  not  so  much  in  the  protein 
content,  perhaps,  as  in  the  very  low  heat  equivalent  (1,600  calories); 
and  a  woman,  with  a  smaller  mass  of  flesh  and  leading  a  less  active  life 
than  a  man,  requires  less  food  of  all  sorts.  Even  the  Trappist  monk, 
who  has  reduced  asceticism  to  a  science,  and,  instead  of  eating  in  order 
to  live,  lives  in  order  not  to  eat,  consumes,  according  to  Voit,  68  grammes 
protein,  11  grammes  fat,  and  469  grammes  carbo-hydrates;  but  manual 
labour  is  a  part  of  the  discipline  of  the  brotherhood,  and  this  must  be 
still  above  the  lowest  subsistence  diet. 

The  question  whether  it  is  best  to  derive  the  proteins  (and  fats)  of 
the  food  mainly  from  plants  or  mainly  from  animals  is  one  which  is 
never  left  to  physiology  alone  to  decide.  But  it  has  been  definitely 
proved  that  vegetable  proteins  and  vegetable  fats  are  (when  properly 
prepared)  digested  and  absorbed  as  completely  as  those  of  animal  origin, 
and  play  the  same  part  in  the  metabolism  of  the  body. 

A  growing  child  needs  far  more  food  than  its  weight  alone  would 
indicate ;  for,  in  the  first  place,  its  income  must  exceed  its  expendi- 
ture so  that  it  may  grow;  and,  in  the  second  place,  the  expenditure 
of  an  organism  is  pretty  nearly  proportional,  not  to  its  mass,  but  to 
its  surface.  Now,  speaking  roughly,  the  cube  of  the  surface  of  an 
animal  varies  as  the  square  of  the  mass;  when  the  weight  is  doubled, 
the  surface  only  becomes  ^^^4,  or  one  and  a  half  times  as  great. 
The  surface  of  a  boy  of  six  to  nine  years,  with  a  body-weight  of 
18  to  24  kilos,  is  two- fifths  to  one-half  that  of  a  man  of  70  kilos; 
and  he  should  have  about  half  as  much  food  as  the  man.  A  child 
of  four  months,  weighing  53  kilos,  consumed  per  diem  food  con- 
taining 0-6  gramme  nitrogen  per  kilo  of  body-weight,  or  318 
grammes  nitrogen  altogether,  as  against  a  daily  consumption  of 
only  0275  gramme  nitrogen  per  kilo  in  a  man  of  71  kilos  (Voit). 

An  infant  for  the  first  seven  months  should  have  nothing  except 
milk.  Up  to  this  age  vegetable  food  is  unsuited  to  it;  it  is  a  purely 
carnivorous  animal.  By  careful  observations  on  the  amount  of 
carbon  dioxide  and  nitrogen  excreted  by  a  child  nine  weeks  old,  fed 
exclusively  on  its  mother's  milk,  it  has  been  shown  that  the  ab- 
sorption and  assimilation  of  milk  in  the  infant  is  very  complete, 
over  91  per  cent,  of  the  total  energy  being  utilized ;  while  an  adult, 
taking  as  much  milk  as  is  necessary  for  the  maintenance  of  nitrog- 
enous equilibrium,  docs  not  utilize  at  most  more  than  84  per  cent. 
Human  milk  contains  about  2  per  cent,  of  protein  (mainly  caseino- 
gcn),  3  per  cent,  of  fat,  5  or  6  per  cent,  of  carbo-hydrate  (lactose  or 
milk-sugar),  and  from  0-2  to  03  per  cent,  of  salts.  Cow's  milk 
contains  about  4  per  cent,  of  protein,  4  to  6  per  cent,  of  fat,  4  per 
cent,  of  lactose*  and  07  per  cent,  of  salts.     When  given  to  infants  it 


DIETETICS  617 

should,  as  a  general  rule,  be  diluted  with  water,  and  some  sugar 
should  be  added  to  it.  Ass's  milk  has  about  the  same  amount  of 
protein,  lactose,  and  salts  as  human  milk,  but  less  than  half  as  much 
fat.     It  is  very  well  borne  and  very  completely  absorbed. 

As  to  the  place  of  water  and  inorganic  salts  in  diet,  it  is  neither 
necessary  nor  practicable  to  lay  down  precise  rules.  In  most  well- 
settled  countries  they  cost  little  or  nothing;  very  different  quantities 
can  be  taken  and  excreted  without  harm ;  and  both  economics  and 
physiology  may  well  leave  every  man  to  his  taste  in  the  matter. 
Salt  is  indeed  for  the  most  part  used,  not  as  a  special  article  of  diet, 
but  as  a  condiment  to  give  a  relish  to  the  food,  just  as  a  great  deal 
more  water  than  is  actually  needed  is  often  drunk  in  the  form  of 
beverages.  It  is  certain  that  the  quantity  of  salt  required,  in 
addition  to  the  salts  of  the  food,  to  keep  the  inorganic  constituents 
of  the  body  at  their  normal  amount,  is  very  small.  When  the  food 
is  entirely  animal,  no  additional  salt  is  necessary.  A  30-kilo  dog 
obtains  in  his  diet  of  500  grammes  of  lean  meat  only  06  gramme 
sodium  chloride,  and  needs  no  more.  An  infant  in  a  litre  of  its 
mother's  milk,  which  is  a  sufficient  diet  for  it  at  six  to  nine  months, 
gets  only  o-8  gramme  sodium  chloride.  The  Hererosin  Damaraland, 
who  are  physically  one  of  the  finest  races  in  Africa,  do  not  use  salt 
(Reclus).  In  this  they  resemble  other  tribes  in  different  parts  of 
the  world  who  eat  no  vegetable  food,  for  example  the  Kirghiz,  who 
live  on  meat  and  milk,  and  the  Todas,  a  pastoral  tribe  in  Southern 
India,  who  are  ignorant  of  the  use  of  vegetable  foods  and  know 
nothing  of  salt  (McCay).  Bunge  has  explained  the  difference 
between  the  flesh  and  the  vegetable  feeder  by  showing  that  the 
proportion  of  potassium  and  sodium  salts  in  the  food  is  a  factor  in 
determining  the  quantity  of  sodium  chloride  required.  A  double 
decomposition  takes  place  in  the  body  between  potassium  phosphate 
and  sodium  chloride,  potassium  chloride  and  sodium  phosphate 
being  formed  and  excreted ;  and  the  loss  of  sodium  and  chlorine  in 
this  way  depends  on  the  relative  proportions  of  potassium  and 
sodium  in  the  food.  In  most  vegetables  the  proportion  of  potassium 
to  sodium  is  much  greater  than  in  animal  food,  so  that  vegetable- 
feeding  animals  and  men  as  a  rule  desire  and  need  relatively  great 
quantities  of  sodium  chloride.  But  it  is  stated  that  the  inhabitants 
of  a  portion  of  the  Soudan  use  potassium  chloride  instead  of  sodium 
chloride,  obtaining  the  potassium  salt  by  burning  certain  plants 
which  leave  an  ash  poor  in  carbonates,  and  then  extracting  the 
residue  with  water  and  evaporating  (Dybowski).  A  beef-eating 
English  soldier  in  India  consumes  about  7  grammes  {\  oz.),  a 
vegetarian  Sepoy  about  18  grammes  (|  oz),  of  common  salt  per  day. 

Stimulants. — Wine,  beer,  tea,  coffee,  cocoa,  etc.,  belong  to  the 
important  class  of  stimulants.  Some  of  them  contain  small  quanti- 
ties of  food  substances,  but  these  are  of  secondary  interest.  In 
beer,  for  example,  there  are  not  inconsiderable  amounts  of  protein'^. 


6i8  METABOLISM,  NUTRITION  AND  DIETETICS 

dextrin,  and  sugar.  But  14  litres  of  beer  would  be  required  to  yield 
15  grammes  nitrogen,  and  10  litres  to  give  250  grammes  carbon; 
and  nobody,  except  a  German  corps  student,  could  consume  such 
quantities.  The  minimum  nitrogen  requirement,  however,  as  well 
as  the  necessary  heat  value,  could  theoretically  be  covered  by  6  or 
7  litres  of  good  German  beer. 

In  some  cocoas  there  is  as  much  as  50  per  cent,  of  fat,  4  per  cent, 
of  starch,  and  13  per  cent,  of  proteins;  and  in  the  cheaper  cocoas 
much  starch  is  added.  Still,  a  large  quantity  of  the  ordinary 
infusion  would  be  needed  for  a  satisfying  meal.  Frederick  the 
Great,  indeed,  in  some  of  his  famous  marches  dined  off  a  cup  of 
chocolate,  and  beat  combined  Europe  on  it ;  but  his  ordinary  menu 
was  much  more  varied  and  substantial. 

Alcohol. — The  great  social  and  hygienic  evils  connected  with  the 
abuse  of  alcohol,  as  well  as  its  applications  in  therapeutics,  render 
it  necessary,  or  at  least  permissible,  to  state  a  little  more  fully, 
though  only  in  the  form  of  summary,  some  of  the  chief  conclusions 
that  may  be  drawn  as  to  its  action  and  uses. 

(i)  In  small  quantities  alcohol  is  oxidized  in  the  body,  a  little  of  it, 
however,  being  excreted  unchanged  in  the  breath  and  urine.  A  certain 
amount  of  protein  is  saved  from  decomposition  when  alcohol  is  taken, 
just  as  when  fat  or  sugar  is  taken.  For  example,  the  addition  of 
130  grammes  of  sugar  to  the  daily  food  of  an  individual  caused  a 
'  sparing  '  of  0-3  gramme  nitrogen.  The  substitution  of  72  grammes 
alcohol  for  the  sugar  caused  0-2  gramme  nitrogen  to  be  spared  (Atwater 
and  Benedict).  Alcohol  is  therefore  to  some  extent  a  food  substance, 
although  it  is  not,  under  ordinary  circumstances,  taken  for  the  sake  of 
the  energy  its  oxidation  can  supply,  but  as  a  stimulant. 

{2)  There  is  no  reason  to  suppose  that  this  energy  cannot  be  utilized 
as  a  source  of  work  in  the  body.  Indeed,  a  certain  amount  of  alcohol 
may  be  normally  formed  in  the  tissues  as  one  of  the  intermediate 
products  in  the  oxidation  of  sugar.  Heat  can  certainly  be  produced 
from  it,  but  this  is  far  more  than  counterbalanced  by  the  increase  in 
the  heat  loss  which  the  dilatation  of  the  cutaneous  vessels  caused  by 
alcohol  brings  about. 

(3)  It  is  a  valuable  drug,  when  judiciously  employed,  in  certain 
diseases — e.g.,  pneumonia  and  puerperal  insanity  (Clouston). 

(4)  Alcohol  is  occasionally  of  use  in  disorders  not  amounting  to 
serious  disease — e.g.,  in  some  cases  of  slow  and  difficult  digestion.  In 
these  cases  it  may  act  by  increasing  the  flow  of  certain  of  the  digestive 
secretions,  as  saliva  and  gastric  juice.  This  effect  seems  to  more  than 
counterbalance  the  retarding  influence  which,  except  when  well  diluted, 
it  exerts  on  the  chemical  processes  of  digestion. 

The  action  of  alcohol  on  the  secretion  of  gastric  juice  has  been  studied 
in  a  dog  with  a  double  gastric  and  oesophageal  fistula.  Before  or 
during  a  sham  meal  of  meat,  alcohol  diluted  with  water  was  given  as 
an  enema.  After  the  enema  the  quantity  of  hydrochloric  acid  secreted 
increased  in  about  the  same  proportion  as  the  quantity  of  juice,  but  the 
pepsin  was  diminished,  reaching  a  minimum  after  three-quarters  to 
one  and  a  quarter  hours.  The  increase  in  the  total  quantity  of  the 
juice  and  in  the  acid  over-compensated  the  moderate  diminution  in  the 
digestive  power,  so  that  the  net  result  was  beneficial  (Pekelharing). 
But  it  must  be  remembered  that  strong  alcoholic  beverages,  when  mixed 


DIETETICS  619 

with  the  gastric  juice,  and  therefore  when  taken  by  the  mouth,  retard 
the  proteolytic  action,  so  that  any  favourable  effect  on  the  secretion  of 
the  juice  may  easily  be  lost  in  the  subsequent  digestion,  unless  the 
alcohol  is  dilute  (Chittenden  and  Mendel).  The  action  of  alcohol  intro- 
duced into  the  rectum  on  the  gastric  secretion  is  both  reflex  and  direct. 

(5)  Alcohol  is  of  no  use  for  health}-  men. 

(6)  Alcohol  in  strictly  moderate  doses*,  properly  diluted  and  especi- 
ally when  taken  with  the  food,  is  not  harmful  to  healthy  men,  living 
and  working  under  ordinary  conditions. 

(7)  Modem  experience  goes  to  show  that  in  severe  and  continuous 
exertion,  coupled  with  exposure  to  all  weathers,  as  in  war  and  in 
exploring  expeditions,  alcohol  is  injurious,  and  it  is  well  known  that  it 
must  be  avoided  in  mountain  climbing. 

Alcohol  in  small  doses,  when  given  by  the  stomach  or  (in  animals) 
injected  into  the  blood,  causes  stimulation  of  the  respiratory  centre  and 
increase  in  the  pulmonary  ventilation.  In  man,  this  increase  usually 
amounts  to  8  to  15  per  cent.,  but  is  occasionally  much  greater.  But  the 
limit  which  separates  the  favourable  action  of  the  small  dose  from  the 
hurtful  action  of  the  large,  is  easily  overstepped.  When  this  is  done, 
and  the  dose  is  continually  increased,  the  activity  of  the  respiratory 
centre  is  first  diminished  and  finally  abolished.  In  dogs,  for  instance, 
after  the  injection  of  considerable  quantities  of  alcohol  into  the  stomach, 
death  takes  place  from  respiratory  failure,  and  the  breathing  stops 
while  the  heart  is  still  imweakened  (Fig.  85,  p.  189).  This  is  the  final 
outcome  of  a  progressive  impairment  in  the  activity  of  the  centre,  of 
which  the  slow  and  heavy  breathing  of  the  drunken  man  represents  an 
earlier  stage. 

Tea,  coffee,  and  cocoa  are  more  suitable  stimulants  for  healthy 
persons,  because  they  are  less  dangerous  than  alcohol,  and  they 
leave  no  unpleasant  effects  behind  them.  But  it  should  be  remem- 
bered that  there  is  no  stimulant  which  is  not  liable  to  be  abused. 
It  has  been  shown  by  ergographic  experiments  (p.  726)  that,  like 
alcohol,  tea,  coffee,  mate,  and  cola-nut,  which  all  contain  the  alka- 
loid theine  or  caffeine,  restore  the  power  of  performing  muscular 
work  after  exhaustion,  but  only  if  food  has  been  recently  or  is 
simultaneously  taken. 

Vitamines. — Certain  substances,  although  neither  in  the  ordinary 
sense  foods  nor  condiments,  seem  to  be  necessary  for  the  main- 
tenence  of  health,  for  in  circumstances  in  which  these  cannot  be 
obtained  for  long  periods  so-called  '  deficiency  diseases,'  such  as 
scurvy,  are  Hable  to  occur.  Scurvy  used  to  be  the  scourge  of  the 
sailing-ship  in  the  days  when  fresh  meat,  and  particularly  fresh 
vegetables  and  fruits,  were  unobtainable  on  long  voyages.  It  has 
long  been  known  that  it  is  prevented  by  the  use  of  lime  or  lemon- 
juice,  in  which  citric  and  a  trace  of  malic  acid  are  contained,  and 
it  used  to  be  thought  that  it  was  the  organic  vegetable  acids  which 
were  the  important  thing.  Recent  researches  have  shown,  how- 
ever, that  scurvy  is  only  one  of  a  group  of  diseases,  including  beri- 
beri, and  probably  pellagra,  rickets,  and  others  which  are  induced 

•  Not  more  than  i\  oz.  of  absohite  alcohol,  corresponding  to  about  4  oz.  of 
whisky,  or  2  to  3  wineglasses  ol  sherry  or  port,  or  a  pint  of  claret,  or  a  couple 
of  pints  of  light  beer  in  24  hours. 


620  METABOLISM,  NUTRITION  AND  DIETETICS 

by  deficiency  in  the  food  of  certain  substances  minute  in  amount 
but  essential  to  proper  nutrition.  These  substances  are  some- 
times termed  '  vitamines.'  But  their  chemical  nature  is  imper- 
fectly known,  and  there  is  no  certainty  that  the  bodies  which  exert 
the  beneficial  influence  belong  to  the  same  chemical  group.*  The 
best  investigated  representative  of  the  important  food  constituents 
in  question  is  a  basic  substance  separated  by  Funk  from  the  polish- 
ings  of  rice,  and  named  by  him  '  vitamine.'  Polished  rice  is  rice 
deprived  of  the  outer  coats  by  modern  milling  processes,  and  the 
pohshings  are  the  coats  which  have  been  removed.  It  is  a  general 
rule  that  the  vitamines  in  the  cereals,  including  wheat,  maize,  oats, 
and  barley,  are  contained  exclusively  in  the  outer  coats.  Since  the 
introduction  of  steel  rollers  instead  of  the  primitive  millstones 
which  used  to  crush  the  whole  grain,  beri-beri,  a  disease  characterized 
by  inflammatory  and  degenerative  changes  in  the  peripheral  nerves 
(peripheral  neuritis)  and  consequent  paralysis,  has  greatly  increased 
among  the  rice-eating  Japanese.  In  Bengal,  although  much  rice 
is  eaten,  there  is  practically  no  beri-beri,  as  country  rice  and  not 
the  highly  polished  variety  is  consumed.  When  birds — e.g.,  pigeons, 
— are  fed  on  polished  rice,  polyneuritis  similar  to  that  seen  in  human 
beri-beri  is  produced,  and  both  in  man  and  in  birds  the  condition 
is  quickly  cured  by  reverting  to  rice  prepared  according  to  the  old- 
fashioned  methods,  or  by  adding  the  polishings  or  an  alcoholic  extract 
of  them  containing  the  essential  substance,  or  the  isolated  base  itself. 

The  addition  of  various  legumes  to  the  diet,  or  alcohohc  extracts 
of  these,  will  produce  the  same  beneficial  effect  (McCay).  Potatoes, 
carrots,  fresh  vegetables,  lime  and  other  fruit  juices,  also  certain 
animal  foods,  such  as  fresh  milk,  fresh  meat,  and  yolk  of  egg,  are 
all  valuable,  in  addition  to  their  ordinary  nutritive  constituents,  for 
their  content  of  vitamines.  Yeast  contains  them  in  exceptionally 
large  amount,  and  it  is  possible,  though  not  proved,  that  such 
fermented  liquors  as  beer,  or  some  varieties  of  it,  may  derive  some 
part  of  their  value  from  these  substances  liberated  both  from  the 
yeast  and  the  barley  and  not  destroyed  in  the  process  of  brewing. 

Since  vitamines  exert  so  great  an  effect  on  nutrition  and  growth, 
it  might  be  expected  that  their  absence  would  tell  on  those  glands 
of  internal  secretion  which  appear  to  be  concerned  in  the  metabolism 
of  growth.  As  a  matter  of  fact,  it  has  been  found  that  in  pigeons 
suffering  from  the  typical  deficiency  disease  beri-beri,  certain  of  these 
glands  show  marked  changes.  The  thymus  gland,  normally  very 
large  and  persistent  in  these  birds,  can  be  caused  to  atrophy  com- 
pletely by  a  diet  of  polished  rice.  Changes  also  occur  in  the  pituitary, 
and  decided  atrophy  in  the  testes  and  ovaries  (Funk  and  Douglas). 

•  It  might  be  better  in  the  present  state  of  our  knowledge  to  avoid  giving 
thcs:;  bodies  a  name  which  may  easily  mislead.  They  might  possibly  be  pro- 
visionally spoken  of  as  "  vitines,"  a  term  involving  no  assumption  as  to  their 
chemical  nature,  and  implying  only  their  importance  in  the  nutritional  pro 
cesses  associated  with  the  life  (and  growth)  of  the  tissues. 


CHAPTER  XI 

INTERNAL  SECRETION 

It  is  long  since  Caspar  Friedrich  Wolff  expressed  the  idea  that 
'  each  single  part  of  the  body,  in  respect  of  its  nutrition,  stands  to 
the  whole  body  in  the  relation  of  an  excreting  organ,'  and  thus 
emphasized  the  importance  of  substances  produced  by  the  activity 
of  one  kind  of  cell  for  the  normal  metaboUsm  of  another.  But  it  is 
only  in  recent  years  that  it  has  become  possible  to  illustrate  this 
mutual  relation  by  any  large  number  of  experimental  facts. 

Certain  of  the  substances  taken  in  from  the  blood  by  the  liver 
find  their  way,  after  undergoing  various  changes,  inio  the  biliary 
capillaries,  and  are  excreted  as  bile;  certain  other  substances,  such 
as  sugar  and  the  precursors  of  urea,  are  taken  up  by  the  hepatic 
cells,  transformed  and  sometimes  stored  for  a  time  wdthin  them, 
and  then  given  out  again  to  the  blood.  Bile  we  may  call  the  external 
secretion  of  the  liver,  glycogen  and  urea  constituents  of  its  internal 
secretion.  In  one  sense  it  is  evident  that  all  tissues,  whether  glands 
in  the  morphological  sense  or  not,  may  be  considered  as  manufac- 
turing an  internal  secretion.  For  everything  that  an  organ  absorbs 
from  the  blood  and  lymph  it  gives  out  to  them  again  in  some  form 
or  other  except  in  so  far  as  it  forms  or  separates  a  secretion  that 
passes  away  by  special  ducts.  But  it  is  usual  to  employ  the  term 
only  in  relation  to  organs  of  glandular  build,  whether  provided  with 
ducts  or  not.  For  convenience  the  action  of  extracts  of  some  other 
tissues,  such  as  nervous  tissue,  will  also  be  considered  here,  although 
there  is  no  reason  to  suppose  that  they  form  any  specific  internal 
secretion. 

The  capacity  of  manufacturing  internal  secretions  of  high  im- 
portance can  neither  be  attributed  to  all  glands  with  ducts  nor 
denied  to  all  other  organs.  For  the  salivary,  mammary,  and  gastric 
glands  may  be  completely  removed  without  causing  any  serious 
effects,  while  death  follows  excision  of  the,  so  far  as  mere  bulk  is 
concerned,  apparently  insignificant  masses  of  tissue  in  the  ductless 
thyroid,  parathyroid,  suprarenal  or  pituitary  bodies. 

It  is  known  that  in  the  case  of  the  liver  the  internal  secretion  is 
more  important  than  the  external,  for  an  animal  cannot  survive 

621 


622  INTERNAL  SECRETION 

without  its  liver,  while  it  may  be  but  little  affected  by  the  con- 
tinuous escape  of  the  bile  through  a  fistulous  opening. 

Pancreas. — The  internal  secretion  of  the  pancreas  is  also  indis- 
pensable. For  when  the  pancreas  is  excised  death  follows  in  many 
species  of  animals,  and  especially  in  carnivorous  animals;  and  in 
man  severe  and  ultimately  fatal  diabetes  is  often  associated  with 
pancreatic  disease,  while  the  mere  loss  of  the  pancreatic  juice 
through  a  fistula  does  not  necessarily  shorten  hfe,  although  the 
absorption  of  fat  is  seriously  interfered  with. 

The  ultimate  cause  of  death  seems  to  be  a  profound  disturbance 
of  metabohsm,  of  which  the  most  significant  token  is  the  increased 
proportion  of  sugar  in  the  blood,  and  its  speedy  appearance  in  the 
urine — in  dogs  always  within  twenty-four  hours  following  total 
removal  of  the  organ.  Associated  with  the  glycosuria  is  an  increase 
in  the  quantity  of  the  urine  (polyuria),  excessive  thirst  (polydipsia), 
and  a  ravenous  appetite  (polyphagia  accompanied  by  intense 
hunger  contractions  of  the  stomach — Luckhardt),  in  spite  of  which 
the  animal  becomes  more  and  more  emaciated — ^in  short,  the 
classical  symptoms  of  a  severe  type  of  pathological  diabetes  in  man, 
but,  of  course,  far  more  acute  in  their  onset,  and  far  more  rapid 
in  their  progress  towards  the  inevitable  end.  Dogs  rarely  survive 
more  than  two  or  three  weeks,  the  immediate  cause  of  the  rapidly 
fatal  result  being  perhaps  the  extensive  suppuration  which  is  apt 
to  ensue  on  slight  and  practically  unavoidable  superficial  injuries. 
The  resistance  of  the  tissues  to  bacterial  invasion  and  their  tendency 
to  spontaneous  healing  are  reduced  by  the  overloading  of  the  blood 
and  tissue  liquids  with  sugar.  Even  when  carbo-hydrates  are  ex- 
cluded from  the  food,  or  when  no  food  at  all  is  given,  sugar  continues 
to  be  excreted  in  large  amounts.  The  destruction  of  proteins  is 
increased.  It  is  a  significant  fact  that  glycosuria  does  not  appear 
or  is  only  transient  when  the  pancreas  is  partially  removed,  so  long 
as  a  comparatively  small  fraction  of  the  gland  (one-quarter  or  one- 
fifth)  is  left.  Even  when  such  a  remnant  is  transplanted  from  its 
original  position,  care  being  taken  not  to  interfere  with  its  circula- 
tion, and  grafted  in  the  peritoneal  cavity  or,  indeed,  under  the  skin, 
the  animal  remains  in  good  health.  In  the  dog  this  operation  can 
be  practised  on  the  lowest  part  of  the  descending  division  of  the 
pancreas,  which  is  not  united  with  the  duodenum,  but  lies  free  in 
the  mesentery.  Removal  of  the  fragment  of  pancreas  is  followed 
by  the  whole  train  of  symptoms  associated  with  total  extirpation 
of  the  organ. 

Although  as  yet  we  are  ignorant  of  the  precise  manner  in  which 
the  pancreas  influences  the  metabolism  of  the  body,  it  is  impossible 
to  doubt,  in  view  of  the  facts  we  have  mentioned,  that,  like  the  liver, 
in  addition  to  carrying  on  the  exchanges  necessary  for  the  prepara- 
tion of  the  ordinary  or  external  secretion,  the   gland  has  other 


PANCREAS  623 

important  relations  with  the  circulating  fluids,  giving  to  them  or 
taking  from  them  substances  on  the  manufacture  or  destruction  of 
which  the  normal  metaboHc  processes  depend.  It  has  been  sug- 
gested that  the  pancreas  neutralizes  or  renders  harmless  some 
toxic  substance  formed  elsewhere  in  the  body,  the  action  of  which 
produces  glycosuria.  But  no  evidence  of  the  existence  of  any  such 
substance  has  been  obtained,  and  the  transfusion  into  a  normal 
dog  of  blood  from  a  depancrcatized  animal,  which  ought  to  be  laden 
with  the  hypothetical  toxic  material,  does  not  cause  glycosuria.  It 
is  much  more  probable  that  the  hyperglycaemia  on  which  the 
glycosuria  depends  is  caused  by  the  absence  of  something  normally 
produced  by  the  pancreas,  and  which  is  indispensable  for  the  due 
regulation  of  the  sugar-content  of  the  blood.  This  something,  as 
already  pointed  out  in  discussing  pathological  diabetes,  may  be 
necessary  to  regulate  the  transformation  of  sugar  into  glycogen, 
or  eventually,  it  may  be,  into  fat,  so  that  too  great  a  surplus  of 
sugar  does  not  remain  unchanged ;  or  to  regulate  the  transformation 
of  glycogen  into  dextrose,  and  prevent  too  hasty  and  too  extensive 
action  by  the  glycogenase;  or  to  regulate  the  production  of  sugar 
from  sources  other  than  the  carbo-hydrates;  or,  finally,  to  regulate 
and  to  aid  in  the  normal  utilization  of  the  sugar  in  the  organs 

(P-  357)- 

While  the  liver  contains  less  than  the  normal  content  of  glycogen, 
its  power  to  form  glycogen  is  certainly  not  abolished.  On  the  con- 
trary, there  is  some  reason  to  think  that  a  great  deal  of  this  reserve 
carbo-hydrate  may  be  S5mthesized  in  the  diabetic  organism,  and 
that  the  comparative  poverty  of  the  hepatic  cells  in  glycogen  may 
be  due  to  rapid  glycogenolysis,  despite  the  hyperglycaemia,  in 
response  to  the  insistent  demand  for  sugar  on  the  part  of  the  tissues, 
which  in  the  midst  of  plenty  are  hungry  for  dextrose  on  account  of 
their  inability  to  utilize  it,  or  some  of  its  decomposition  products, 
in  the  normal  way.  It  has  indeed  been  shown  by  numerous  ex- 
periments that  interference  with  the  formation  or  with  the  hydrol- 
ysis of  glycogen,  although  it  may  be  a  factor,  is  not  of  itself  sufficient 
to  explain  pancreatic  glycosuria. 

Failure  in  the  katabolism  of  dextrose,  as  already  mentioned 
(p.  545),  has  been  asserted  by  some  observers  and  denied  by  others. 
A  great  production  of  sugar  from  proteins  (i.e.,  from  amino-acids) 
has  been  demonstrated,  but  it  is'quite  possible  that  just  as  much  is 
produced  from  this  source  in  the  normal  organism,  although  here 
its  formation  is  masked  by  a  corresponding  utilization. 

The  clearest  evidence  that  the  pancreas  produces  something  of 
high  importance  in  carbo-hydrate  metabolism  has  been  obtained 
by  experiments  in  which  animals  were  united  in  such  a  way 
that  substances  could  pass  from  one  to  the  other  (parabiosis,  see 
Chap.  XIX.).   When  two  young  dogs  were  so  united  and  the  pancreas 


624  INTERNAL  SECRETION 

then  removed  from  one,  no  glycosuria  followed.  The  internal 
secretion  of  the  remaining  pancreas  was  sufficient  for  both  (Forsch- 
bach).  In  like  manner  the  removal  of  the  pancreas  from  pregnant 
bitches  not  far  from  full  term  caused  no  glycosuria  or  very  little 
till  the  pups  were  born,  when  the  usual  train  of  events  associated 
with  pancreatic  diabetes  ensued.  Obviously  the  pancreatic  tissue 
of  the  embryos  in  the  uterus  supplied  the  mother  with  the  indis- 
pensable secretion  (Carlson  and  Drennan). 

The  question  has  often  been  raised  why  it  should  not  be  possible 
to  supply  animals  or  human  beings  suffering  from  pancreatic  defi- 
ciency with  the  missing  material  by  administering  pancreas  or 
pancreatic  extracts.  Hitherto,  however,  little  if  any  success  has 
attended  attempts  of  this  kind,  perhaps  because  the  active  substance 
or  substances  are  very  easily  destroyed.  This  has  been  all  the  more 
disappointing,  as  in  the  case  of  the  internal  secretion  of  the  thyroid 
the  so-called  '  substitution  therapy  '  has  been  brilliantly  successful 

(P-  634)- 

The  seat  of  the  internal  secretion  of  the  pancreas  seems  to  be  the 
very  vascular  epithelioid  tissue  which  is  peculiar  to  this  gland,  and 
occurs  in  islands  between  or  imbedded  in  the  alveoU  (islands  or 
islets  of  Langerhans)  (Schafer).  Fur  animals  survive  the  complete 
atrophy  of  the  ordinary  secreting  epithelium  caused  by  the  injec- 
tion of  paraffin  into  the  ducts,  and  no  sugar  appears  in  the  urine. 
The  islets  remain  intact.  When  a  portion  of  the  pancreas  is 
separated  from  the  rest,  and  its  duct  ligated,  it  undergoes  extensive 
atrophy,  a  tissue  remaining  which  is  apparently  composed  of  en- 
larged islands  of  Langerhans  and  remains  of  pancreatic  ducts.  If 
the  rest  of  the  gland  is  now  removed,  no  glycosuria  occurs,  even 
when  considerable  quantities  of  dextrose  are  injected.  But  when 
the  atrophied  remnant  is  also  removed,  typical  pancreatic  glycosuria 
at  once  ensues  (W.  G.  MacCallum) . 

As  further  evidence  that  the  islets  have  a  different  function  from 
the  pancreatic  alveoli  may  be  cited  the  statement  that  in  teleostean 
fishes,  in  which  the  islands  are  so  large  that  they  can  be  separated 
from  the  rest  of  the  tissue,  the  cells  of  the  islets,  instead  of  containing 
an  amylolytic  ferment  like  the  alveolar  cells,  contain  a  glycolytic 
ferment,  or  at  least  possess  the  power  of  destroying  sugar.  Yet  the 
question  of  the  significance  of  the  islets  can  hardly  be  considered 
settled,  although,  as  previously  mentioned,  the  supposed  experi- 
mental basis  of  the  theory  that  they  do  not  differ  essentially  from 
the  alveolar  tissue,  but  are  formed  by  certain  changes  in  the  arrange- 
ment and  properties  of  the  alveolar  elements,  appears  to  have 
collapsed  under  the  criticism  of  Bensley  and  others.  Far  from 
being  interchangeable  with  the  cells  of  the  acini,  the  islet  cells 
present  definite  and  permanent  criteria  by  which  they  can  be  sharply 
distinguished  from  the  alveolar  epithelium.      At  least  two  types  of 


PANCREAS  625 

islet  cells  may  be  identified  by  their  staining  reactions,  the  so-called 
A  and  B  cells  (Lane).  The  B  cells  are  the  most  abundant  in 
all  the  islets,  and  many  of  the  small  islets  are  composed  of  them. 
In  the  guinea-pig,  on  account  of  the  great  size  of  some  of  the  islets, 
and  because  many  of  them  arc  situated  in  the  interstitial  tissue 
(between  the  acini),  it  is  not  difficult  to  pick  out  an  islet,  isolate  it 
from  the  surrounding  tissue,  and  examine  it  in  serum  or  salt  solu- 
tion. The  cells  are  crowded  with  very  fine  granules  exhibiting 
Brownian  movement.  In  the  fresh  preparation  the  granules  of  the 
A  cells  cannot  be  distinguished  from  those  of  the  B  cells. 
Both  varieties  stain  intensely  with  neutral  red  and  other  dyes,  and 
the  islet  tissue  can  in  this  way  be  easily  differentiated  from  the 
tissue  of  the  acini.  By  differences  in  their  staining  reactions  and 
certain  properties  of  their  nuclei,  which  need  not  be  gone  into  here, 
the  two  varieties  of  islet  cells  can  be  identified.  The  important 
point  for  our  purpose  is  that  by  an  appropriate  histological  tech- 
nique the  islet  tissue  can  be  studied  in  all  the  functional  vicissitudes 
of  the  gland.  When  this  is  properly  done,  it  is  not  found  that 
there  is  any  close  connection  between  the  secretory  activity  of  the 
cells  of  the  acini  and  the  islets.  Nor  is  there  any  evidence  that  the 
amount  of  islet  tissue  in  the  pancreas  is  ever  affected  by  the  forma- 
tion of  new  islets  out  of  acini.  On  the  other  hand,  it  seems  that  the 
islets,  or  the  great  majority  of  them,  consist  of  epithelial  cells  which 
are  in  direct  continuity  with  the  pancreatic  ducts,  and  that  after 
removal  of  a  portion  of  the  pancreas,  estabhshing  an  insufficiency  of 
islet  tissue,  new  islets  can  be  developed  from  the  duct  epithelium, 
in  addition  to  the  increase  by  interstitial  growth  in  the  size  of  islets 
already  existing  (Bensley,  etc.).  If  the  islets  are  connected  with 
the  ducts,  the  possibility  may  be  admitted  that  they  yield  some- 
thing to  the  external  secretion  of  the  pancreas  as  well  as  to  its 
internal  secretion.  But  if  this  be  so,  there  is  no  improbability  in 
the  idea  that  the  alveolar  epithelium,  which  is  undoubtedly  mainly 
concerned  in  the  preparation  of  the  pancreatic  juice,  may  also 
contribute  something  to  the  internal  secretion  of  the  gland.  While, 
then,  the  importance  of  the  pancreas  in  carbo-hydrate  metabohsm 
is  certain,  and  the  dependence  of  this  function  upon  an  internal 
secretion  is  highly  probable,  it  is  not  yet  definitely  settled  whether 
this  secretion  is  formed  in  the  organ  as  a  whole,  or  only  in  the  islets. 
That  lesions  of  the  pancreas  may  be  concerned  in  pathological 
diabetes  is  well  established,  and  it  is  of  interest  in  connection  with 
the  question  we  have  just  been  discussing  that  in  a  certain  number 
of  cases  the  changes  observed  have  been  in  the  islands  (Opie).  And 
in  diabetes  accompanying  cirrhosis  of  the  liver,  which  has  usually 
been  considered  to  depend  upon  the  hepatic  changes,  it  has  been 
shown  that  in  many,  if  not  all,  of  the  cases  the  pancreas  is  also 
affected  by  a  growth  of  connective  tissue  outside  the  acini  (Stein- 

40 


626  INTERNAL  SECRETION 

haus).  Some  authors,  indeed,  have  gone  so  far  as  to  say  that  in  all 
cases  of  diabetes  mellitus  there  is  disease  of  the  pancreas,  but  of  this 
there  is  no  evidence. 

Ligation,  or  the  establishment  of  a  fistula,  of  the  thoracic  duct, 
causes  glycosuria  in  dogs.  It  is  possible  that  this  is  really  a  mild 
form  of  pancreatic  diabetes,  due  to  interference  with  the  supply  of 
the  internal  secretion  of  the  pancreas,  or  of  that  part  of  it  which 
reaches  the  blood  by  the  lymph- stream  (Tuckett). 

Pfliiger  has  brought  forward  evidence  that  it  is  not  the  removal  of  the ' 
pancreas,  as  such,  but  the  section  of  certain  nerves  running  into  or 
through  it  from  the  duodenum,  which  is  the  cause  of  the  glycosuria. 
For  when  these  nerves  are  divided  or  the  duodenum  removed  while  the 
pancreas  remains  untouched,  the  result  is  the  same  as  if  the  pancreas 
itself  had  been  excised.  He  imagines  that  these  nerves  are  '  anti- 
diabetic ' — that  is,  in  some  way  oppose  tlie  production  of  sugar — while 
nerves  coming  from  the  so-called  '  sugar  centre  '  in  the  bulb  (the  centre 
assumed  to  be  affected  in  the  puncture  experiment)  favour  sugar  pro- 
duction. Between  these  the  normal  balance  is  struck  in  health;  it  is 
the  upsetting  of  this  balance  by  the  crippling  of  the  duodenal  fibres 
which  is  at  the  bottom  of  '  pancreatic  '  diabetes.  It  is  too  early  to 
appraise  the  value  of  this  conception,  especially  as  the  facts  upon  which 
it  is  founded  have  only  been  clearly  established  for  frogs,  and  it  is 
doubtful  whether  they  can  be  extended  to  mammals.  But  if  these  nerves 
end  in  the  pancreas,  and  do  not  simply  run  through  it,  say,  to  the 
liver,  it  is  possible  that  they  act  on  the  sugar  metabolism  by  regulating 
the  internal  secretion  of  the  pancreas. 

Sexual  Organs. — The  influence  of  castration  in  preventing  the 
development  of  the  sexual  characters,  and  especially  the  physical 
and  psychical  changes  that  normally  occur  at  puberty,  is  also  due 
to  the  loss  of  the  internal  secretion  of  the  generative  glands,  and 
does  not  appear  to  depend  at  all  upon  the  loss  of  nervous  impulses 
arising  in  these  organs.  In  Herdwick  sheep  an  outstanding  sexual 
difference  is  the  presence  of  horns  in  the  males,  their  absence  in 
the  females.  Removal  of  the  testes  from  ram  lambs  arrests  further 
growth  of  horns  forthwith  and  at  any  stage  of  development.  The 
retention  of  the  epididymes,  provided  that  the  testes  proper  are 
removed,  does  not  alter  the  result  of  castration  in  the  least.  The 
removal  of  one  testicle  slows  horn  growth  without  arresting  it 
(Marshall  and  Hammond).  In  partially  castrated  cocks  it  has  been 
seen  that,  so  long  as  a  portion  of  one  testicle  remains,  the  male 
characters  are  preserved,  but  after  removal  of  this  residue  the 
comb  and  wattles  wither  in  a  few  weeks  (Hanau).  At  the  breeding- 
time  the  muscles  of  the  forearm  of  the  brown  land  frog  [Rana 
fusca)  become  hypertrophied  in  the  male,  so  that  it  can  more  tightly 
hold  the  female.  At  the  same  time  the  balls  of  the  toes  increase 
in  size,  and  become  covered  with  a  pecuUar  black  growth.  After 
the  breeding  season  these  secondary  sexual  characters  disappear. 
If  the  male  frog  is  castrated,  the  periodic  return  of  these  phenomena 
does  not  occur,  but  the  presence  of  one  testicle  suffices  for  their 


SEXUAL  ORGANS  '  627 

development  on  both  sides.  When  pieces  of  testicle  from  normal 
frogs  are  introduced  under  the  skin  of  the  castrated  frogs,  the 
phenomena  occur  just  as  if  the  animals  had  not  been  castrated 
(M.  Nussbaum). 

The  remarkable  observations  of  Steinach  indicate  that  the 
internal  secretion  is  not  furnished  by  the  proper  reproductive 
elements  (those  which  form  the  spermatozoa),  but  by  the  interstitial 
cells  of  Leydig,  which  are  distributed  in  groups  throughout  the 
substance  of  the  testes  between  the  seminal  tubules.  When  the 
testes  of  a  young  rat  or  guinea-pig  are  transplanted  to  another  part 
of  its  body  (the  peritoneal  cavity  or  subcutaneous  tissue),  the 
animal  develops  all  the  secondary  sexual  characters  at  the  proper 
time.  The  penis  grows  to  the  normal  size.  .The  seminal  vesicles 
and  prostate  develop  in  the  ordinary  way,  and  3aeld  a  plentiful 
secretion.  Sexual  desire  and  potency  appear  in  due  season,  and 
in  normal  or,  in  not  a  few  cases,  indeed,  increased  intensity.  Yet 
histological  examination  shows  that  not  a  single  spermatocyte  or 
spermatid  (Chapter  XIX.)  has  developed,  while  outside  the 
seminal  tubules  the  interstitial  cells  forrn  large  masses  which  much 
surpass  in  size  the  interstitial  islands  of  the  normal  testis.  Similar 
changes  are  observed,  though  with  less  certainty  and  after  a  longer 
interval,  when  the  vas  deferens  is  ligated,  a  method  often  recom- 
mended and  occasionally  practised  for  the  sterihzation  of  the  human 
male.  On  account  of  the  influence,  thus  demonstrated,  of  the  inter- 
stitial cells  in  producing  the  sexual  development  observed  at  puberty, 
Steinach  designates  these  cells  collectively  as  the  '  puberty  gland.' 

When  the  ovaries  of  a  3'oung  female  rat  or  guinea-pig  are 
transplanted  into  the  peritoneal  cavity  or  under  the  skin  of  a  pre- 
viously castrated  male  animal  of  the  same  kind  (preferably,  to 
facilitate  accurate  comparison,  a  male  of  the  same  litter),  the  graft 
takes  (in  about  half  the  cases),  and  the  implanted  ovaries  grow 
and  mature  in  the  male  body.  There  is  this  difference  in  the  fate 
of  the  ovary  and  the  testis  when  transplanted,  that  the  generative 
elements  of  the  latter,  the  Graafian  follicles,  with  the  ova  contained 
in  them,  generally  develop  as  well  as  the  large  interstitial  cells  rich 
in  protoplasm  lying  in  the  stroma,  which  cells  appear  to  constitute 
the  female  puberty  gland.  The  strict  isolation  of  the  female 
puberty  gland  is  only  realized  in  those  cases  in  which  by  some 
accident  of  healing  the  stroma  of  the  transplanted  ovary  maintains 
itself  while  the  generative  elements  disappear.  In  these  cases  the 
influence  of  the  ovary  on  the  development  of  the  sexual  characters 
is  the  same  as  when  the  reproductive  elements  proper  persist  and 
grow.  Male  animals  into  which  successful  implantation  of  ovaries 
has  been  accomphshed,  instead  of  developing  sexually  in  the  way 
observed  even  in  castrated  males,  become  feminized.  The  growth 
of  the  external  generative  organs  is  inliibited,  the  mammary  glands 


628  INTERNAL  SECRETION 

and  the  nipples  develop  to  the  form  and  size  seen  in  the  normal 
female.  The  dimensions  and  shape  of  the  body  conform  more  and 
more  to  the  feminine  type.  The  hair  becomes  smooth  and  silky, 
in  contrast  to  the  coarse  hair  of  the  normal  or  even  of  the  castrated 
male.  The  psychical  characteristics  also  become  feminized,  and 
certain  reflexes  peculiar  to  the  female  make  their  appearance.  The 
feminized  male  is  sought  by  normal  males  as  if  it  were  a  true  female. 

A  more  general  influence  of  the  sexual  organs  on  metabohsm 
seems  also  to  be  well  established.  The  exact  experiments  of  Loewy 
and  Richter  on  the  metabolism  of  bitches  before  and  after  cas- 
tration throw  light  upon  the  changes  which  follow  that  operation, 
and  afford  decisive  proof  that  they  are  connected  with  the  absence 
of  substances  specific  to  the  ovary.  They  conclude  that  in  the 
castrated  animal  the  oxidative  energy  of  the  cells  is  lessened.  The 
oxygen  consumption  sinks,  even  although  protein  is  laid  on  and  the 
total  amount  of  active  tissue  thus  increased.  Under  certain  cir- 
cumstances this  specific  diminution  of  metabolism  may  be  balanced 
by  conditions  which  cause  an  increase  in  the  metabolism.  The 
lessening  of  the  oxidative  power  is  due  to  the  loss  of  ovarian  sub- 
stance, for  the  administration  of  an  extract  of  the  ovary  (oophorin) 
not  only  neutrahzes  it,  but  actually  causes  an  increase  in  the  gaseous 
metabolism  to  far  above  the  original  amount,  while  it  has  no  effect 
on  the  metabolism  of  the  uncastrated  animal.  It  is  not  the  de- 
composition of  proteins,  but  of  non-nitrogenous  substances,  which 
is  accelerated.  Oophorin  also  brings  about  a  notable  increase  in 
metabolism  in  the  castrated  male  dog,  while,  curiously  enough, 
extract  of  testicle  causes  only  a  small  increase,  due  to  a  basic  sub- 
stance, spermin  (C5Hj4N2),  which  can  be  isolated  from  the  testicle. 
But  the  orchitic  extract  is  not  without  influence  in  other  ways. 
It  certainly  increases  the  capacity  for  muscular  work  (Zoth  and 
Pregl),  as  tested  by  the  ergograph  (p.  726),  and  this  distinct  physio- 
logical action  is  sufficient  to  encourage  the  hope  that  it  may  possess 
some  therapeutic  value,  although  far  from  what  has  been  claimed 
for  it  by  its  more  enthusiastic  advocates.  The  only  constituent  of 
extracts  of  the  testicle  made  with  salt  solution  which  causes  any 
pronounced  effect  on  the  blood-pressure  when  injected  into  the 
circulation  is  a  nucleo-protein,  the  most  plentiful  of  the  protein 
substances.  The  pressure  falls,  mainly  owing  to  inhibition  of  the 
heart,  but  partly  through  vaso-dilatation  in  the  splanchnic  area 
(Dixon). 

The  testicles  also  influence  the  growth  of  the  bones.  In  eunuchs 
and  in  young  men  with  atrophy  of  the  testicles  a  tendency  has  been 
observed  for  the  long  bones  to  go  on  growing  far  beyond  the  usual 
period.  This  has  been  shown  by  the  Rontgen  rays  to  be  due  to 
delay  in  the  ossification  of  the  epiphyses.  The  same  has  been 
observed  in  animals,  and  is  supposed  to  be  caused  by  the  loss  of 


THYMUS  629 

some  substance  normally  formed  in  the  testicle  which  influences  the 
metabolism  of  the  bones  and  the  deposition  of  the  bone  salts. 

A  temporary  diminution  in  the  haemoglobin  and  in  the  number 
of  the  erythrocytes  has  been  observed  in  castrated  bitches,  an 
observation  which,  so  far  as  it  goes,  is  in  favour  of  the  view  that  an 
insufficient  internal  secretion  of  the  ovaries  is  the  cause  of  the 
form  of  anaemia  kno^vn  as  chlorosis. 

While  these  effects  on  general  metabolism  and  nutrition,  as  well 
as  the  influence  on  the  development  of  the  sexual  characters,  are 
probably  to  be  ascribed  to  changes  in  the  internal  secretion  of  the 
interstitial  cells,  there  are  facts  which  indicate  that  other  elements 
may  be  concerned.  For  example,  evidence  has  been  brought 
forward  that  the  corpus  luteum  is  a  gland  with  an  internal  secretion, 
whose  function  is  connected  with  menstruation  and  wth  the  im- 
plantation of  the  ovum  and  the  subsequent  growth  of  both  ovum 
and  utcius  in  pregnancy  (Born,  Fraenkel)  (Chap.  XIX.). 

Thymus. — Our  knowledge  of  the  function  of  the  thymus  is  very 
incomplete.  Even  its  histological  structure,  and  especially  the 
source  and  nature  of  its  cellular  elements,  have  long  been,  and  still 
are,  the  subject  of  controversy.  It  is  developed  as  a  pair  of  diver- 
ticula from  the  ventral  part  of  the  third  and  fourth,  perhaps  also 
to  some  extent  from  the  second,  branchial  cleft.  These  pouches 
grow  downwards  into  the  thorax.  At  this  stage  the  organ  is  a 
purely  epithelial  structure.  Soon  connective  tissue  and  blood- 
vessels begin  to  grow  into  it,  the  two  halves  coalesce  in  the  middle 
line,  and  the  thymus  becomes  transformed  by  degrees  into  a  struc- 
ture with  a  general  resemblance  to  a  big  lymph  gland,  and  con- 
sisting mainly  of  small  cells  like  lymphocytes.  Some  observers 
believe  that  these  cells  are  true  lymphocytes,  derived  from  the 
mesoderm,  which  have  migrated  into  and  displaced  the  earher 
epithelial  tissue.  Others  maintain  that  the  resemblance  is  merely 
superficial,  and  that  they  are  simply  epithelial  cells  diminished  in 
size  and  altered  in  shape,  but  derived  from  the  original  epithelium 
by  repeated  division,  and  remaining  epithelial  to  the  end.  Any 
theory  of  the  function  of  the  thymus  must  needs  depend  largely 
upon  the  view  adopted  as  to  its  structure.  For  if  it  is  in  its  fully 
developed  state  merely  a  large  collection  of  lymphocytes,  it  would 
appear  quite  unlikely  that  it  should  possess  functions  very  different 
from  those  of  other  collections  of  lymphocytes.  On  the  other 
hand,  if  the  essential  elements  in  the  organ  are  epithelial,  they  may 
well,  like  the  epithelial  elements  of  the  thyroid  or  of  other  glands 
with  an  internal  secretion,  be  concerned  in  the  elaboration  of  sub- 
stances which  exercise  an  important  influence  upon  nutrition  and 
growth.  On  the  whole,  the  best  histological  evidence  seems  to 
favour  the  view  that  the  thymus  cells  are  different  from  the  cells 
of  lymph  glands.     Chemical  differences  also  exist.     For  example. 


630  INTERNAL  SECRETION 

nuclein  substances  characteristic  of  the  nuclear  framework  of  the 
true  glands  are  much  more  abundant  in  the  thymus  than  in  lymph 
glands. 

After  a  period  of  further  development,  which  varies  in  duration 
in  different  animals,  the  organ  undergoes  involution.  In  mammals 
(including  man)  the  thymus  does  not  completely  disappear  in  the 
adult.  Islands  of  thymus  tissue  are  found  at  all  ages  among  the 
fat  by  which  the  bulk  of  the  organ  is  replaced.  It  is  usually  stated 
that  in  man  the  thymus  begins  to  diminish  in  size  about  the  end  of 
the  second  year,  but  the  careful  observations  of  Hammar  indicate 
that  this  is  incorrect.  According  to  him,  the  organ  continues  to 
grow  till  puberty  is  reached,  weighing  on  the  average  13  grammes 
at  birth,  37  grammes  at  eleven  to  fifteen  years,  25  grammes  at 
sixteen  to  twenty  years,  and  only  6  grammes  at  sixty-six  to  seventy- 
five  years.  Besides  this  involution  with  age,  great  changes  in  the 
size  of  the  thymus  may  occur  at  any  time  under  the  influence  of 
toxic  substances  or  of  deficient  nutrition.  In  starvation,  even  in 
the  first  three  days  of  hunger,  the  weight  of  the  thymus  in  rabbits 
has  been  observed  to  shrink  to  one-half,  and  during  prolonged 
underfeeding  even  to  one-thirtieth,  of  the  normal  (Jonson).  The 
opposite  effect,  namely,  cessation  of  the  involution  process,  or 
even  new  formation  of  thymus  tissue,  may  also  occur,  leading  to 
the  presence  of  an  unusually  large  so-called  persistent  thymus  in 
the  adult. 

The  point  most  clearly  estabhshed  in  the  physiology  of  the 
thymus  seems  to  be  its  relation  to  the  sexual  glands.  It  is  well 
known  that  in  castrated  animals  the  thymus  is  larger  and  persists 
longer  than  in  entire  animals.  In  bulls  and  unspayed  heifers  the 
normal  atrophy  of  the  thymus,  which  begins  after  the  period  of 
puberty,  is  greatly  accelerated  when  the  bulls  have  been  used  for 
breeding,  and  when  the  heifers  have  been  pregnant  for  several 
months.  There  is  a  reciprocal  influence  of  the  thymus  on  the 
testicles,  and  removal  of  the  thymus  before  the  time  at  which  it 
naturally  atrophies  is  followed  by  a  more  rapid  growth  of  the  testes 
(in  guinea-pigs)  (Paton).  The  relation  of  the  thymus  to  the  growth 
of  bones  is  less  well  established,  but  according  to  some  observers 
extirpation  of  the  gland  retards  their  calcification. 

In  young  mammals  the  loss  of  the  thymus  is  said  to  cause  transient 
disturbances  of  nutrition,  a  temporary  decrease  in  the  number  of 
all  varieties  of  leucocytes,  and  a  diminished  resistance  to  the  pus- 
forming  micrococci,  probably  connected  with  the  relatively  feeble 
leucocytosis  (or  increase  in  the  number  of  leucocytes)  by  which  the 
animals  react  to  the  infection.  In  the  frog  the  thymus  persists 
throughout  life.  Yet  the  removal  of  it  is  not  fatal  if  precautions 
against  infection  be  taken. 

The  chief  effect  of  intravenous  injection  of  extract  of  human 


THYROIDS  AND  PARATHYROIDS 


631 


\^& 


SD-m 


or  ox  thymus  is  a  lowering  of  bl ood- pressure ;  but  there  is  nothing 
specific  in  this,  a  similar  effect  being  given  by  thyroid  extract  and 
the  extracts  of  many  other  tissues.  The  heart  may  be  at  the  same 
time  accelerated. 

Thyroids  and  Parathyroids. — The  thyroid  consists  of  two  lobes 
connected  by  an  isthmus  across  the  middle  line  in  man  and  some 
animals,  but  often  separate.  In  the  neighbourhood  of  the  thyroid, 
or  embedded  in  its  tissue,  are  certain  bodies  called  parathyroids, 
consisting  of  solid  columns  of  epithelial  cells.  The  number  and 
situation  of  the  parathyroids  are  not  constant.  As  a  rule,  there  are 
four  in    mammals,    two    on  ^ 

each  side,  but  this  number 
is  subject  to  variations  in 
different  individuals  of  the 
same  species.  The  varia- 
bility in  their  anatomical 
relations  to  the  thyroid  is 
of  greater  significance.  For 
much  of  the  uncertainty  in 
which  the  whole  question  of 
the  symptoms  following  ex- 
tirpation of  the  thyroids  was 
until  lately  involved  arose 
from  ignorance  or  insufficient 
recognition  of  this  variabiUty. 
In  most  animals  the  inferior, 
anterior,  or  external  pair  of 
parathyroids  is  more  or  less 
distinctly  separated  from  the 
thyroid.  The  separation  is 
especially  evident  in  the  her- 
bivora,  in  the  monkey,  and 
in  man,  and  this  pair  of  para- 
thyroids is  much  larger  than 
the  other.  In  carnivorous 
animals,  as  the  dog  and  cat, the  anterior  pair  of  parathyroids  is  closely 
adherent  to  the  thyroid  capsule.  The  superior,  posterior,  or  internal 
pair,  both  in  herbivora  and  carnivora,  is  always  very  closely  associ- 
ated with  the  capsule  of  the  thyroid,  and  frequently  embedded  in  the 
substance  of  the  gland.  The  consequence  of  this  arrangement  is 
that  in  the  older  experiments  the  chief  masses  of  parath}Toid  tissue 
were  much  more  likely  to  escape  removal  with  the  thyroid  in  the 
case  of  herbivorous  than  in  the  case  of  carnivorous  animals. 

But  even  in  one  and  the  same  species  considerable  variations  may 
exist.  It  is  easy  to  see,  then,  that  in  removing  the  th\Toid  the 
parathyroids  would   sometimes  be  completely  removed  as  well. 


Fig.  202. — Parathyroid  (Vincent  and  Jolly). 
A  small  portion  of  parathyroid  of  cat  em- 
bedded in  thyroid  tissue.  It  consists  for 
the  most  part  of  solid  columns  of  epithelial 
cells  (3,  5,  8)  with  strands  of  vascular  con- 
nective tissue  (6).  A  th\Toid  vesicle  (11) 
and  portions  of  two  others  (i,  10)  are  seen 
in  the  lower  part  of  the  figure,  separated 
from  the  parathyroid  by  a  fibrous  capsule 
(2).  4,  7,  bloodvessels;  9,  lower  boundary 
of  the  parath^Toid  tissue.     {  x  500.) 


632  INTERNAL  SECRETION 

while  at  other  times  all  or  some  of  the  parathyroid  tissue  would  be 
spared.  Add  to  this  that  sporadic  masses  of  thyroid  tissue  (acces- 
sory thyroids),  often  existing  as  far  down  as  the  root  of  the  aorta 
(always,  indeed,  in  certain  animals — e.g.,  the  dog),  must  necessarily 
be  spared  in  the  most  complete  thyroidectomy,  and  it  will  cease  to 
excite  surprise  that  the  symptoms  and  pathological  changes  de- 
scribed after  that  operation  should  have  been  so  various  and  so 
contradictory.  We  know  now  that  the  parathyroids  are  perfectly 
distinct  organs  from  the  thyroid  in  histological  structure,  in  func- 
tion, and  in  the  consequences  of  their  removal.  The  parathjToids, 
for  instance,  contain  no  iodine,  while  iodine  is  a  characteristic 
constituent  of  the  thyroid.  Nor  do  the  parathyroids  show  any 
compensatory  hypertrophy  when  the  thyroid  alone  is  excised,  or 
any  changes  which  would  indicate  a  definite  relation  to,  still  less  an 
active  participation  in,  the  pathological  processes  occurring  in  the 
thyroid  in  goitre.  This  does  not  mean,  however,  that  there  are 
no  points  of  contact  between  the  functions  of  the  two  glands.  The 
more  the  matter  is  probed,  the  more  clearly  does  it  appear  that  none 
of  the  organs  is  quite  independent  of  the  rest,  and  the  reciprocal 
relations  of  the  ductless  glands  are  probably  of  exceptional  im- 
portance. But  the  premature  attempts  which  have  been  made, 
in  the  absence  of  a  sufficiency  of  exact  data,  to  represent  their 
mutual  influence  by  crude  schemata,  have  retarded  rather  than 
advanced  our  knowledge,  and  need  not  be  referred  to  here. 

Parathyroidectomy. — Total  extirpation  of  the  parathyroids  is 
followed  by  a  train  of  acute  symptoms,  ending  fatally,  as  a  rule,  in 
from  one  to  ten  days.  The  typical  nervous  symptoms  following  the 
operation  have  been  described  as  those  of  '  tetany,'  and  the  tetany 
which  used  to  be  included  among  the  consequences  of  removal  of 
the  thyroid  is  now  known  to  be  due  to  the  simultaneous  excision 
of  the  parathyroids  (Kocher).  A  cat,  after  the  combined  operation, 
is  perfectly  well  on  the  first  day.  On  the  second  day  a  curious 
shaking  of  the  paws  is  seen,  tremors  of  central  origin  soon  appear, 
and  increase  in  severity,  until  at  length  they  culminate  in  general 
spasmodic  attacks.  Even  when  the  animal  is  at  rest  the  fore-legs 
tend  to  be  flexed,  while  the  hind-legs  are  extended,  and  this  attitude 
is  exaggerated  in  the  convulsions.  In  the  later  stages  unconscious- 
ness is  associated  with  the  onset  of  the  convulsions.  Similar  results 
follow  excision  of  the  parathyroids  alone  in  dogs.  Although  the 
tetany  is  the  most  striking  symptom,  it  is  only  one  token  of  a  pro- 
found general  disturbance  of  nutrition.  The  pulse-rate  and  the 
rate  of  respiration  are  markedly  increased.  There  is  fever  and  pro- 
fuse salivation,  with  dilatation  of  the  stomach  and  duodenum,  due 
to  the  loss  of  muscular  tonicity.  In  the  intervals  between  attacks 
the  tonus  returns  to  the  normal.  The  secretion  of  the  gastric 
juice,  pancreatic  juice,  and  bile  are  interfered  with  (Carlson,  etc.). 


THYROIDS  AND  PARATHYROIDS  633 

The  excitability  of  the  vaso-constrictor  mechanism  is  said  to  be 
increased.  The  exact  significance  of  these  symptoms  is  unknown 
It  has  been  suggested  that  the  loss  of  the  parathyroid  function  is 
in  some  way  associated  with  an  augmentation  of  the  irritability  of 
the  whole  sympathetic  system  (Hoskins).  The  administration  of 
calcium  completely  relieves  the  symptoms,  and  by  its  use  death  may 
be  long  or  perhaps  indefinitely  postponed  (W.  G.  MacCallum).  The 
mode  of  action  of  the  calcium  has  not  been  made  clear  as  yet.  It 
does  not  seem  to  be  so  efficacious  in  rabbits  as  in  dogs  (Arthus). 

Thyroidectomy. — The  symptoms  that  follow  removal  of  the 
th^Toid  alone  are  perfectly  different.  The  metaboUc  disturbance  is 
eventually,  in  most  animals,  not  less  far-reaching  than  that  which 
ensues  when  the  parathyroids  are  alone  excised.  But  it  is  far  more 
chronic,  reveals  itself  by  totally  distinct  changes,  is  not  amenable 
to  calcium,  and  is  completely  corrected  by  the  administration  of 
thyroid  substance.  While  no  animals  which  have  been  examined 
survive  the  total  removal  of  the  parathyroids,  certain  species — 
e.g.,  the  goat — are  but  slightly  afected  by  thyroidectomy,  and 
survive  indefinitely.  In  man,  before  the  consequences  of  thyroid- 
ectomy were  known,  the  whole  gland  was  not  infrequently  excised 
for  goitre.  If  the  parathyroids  happened  also  to  be  completely 
involved  in  the  operation,  death  quickly  followed.  But  where  only 
the  th}Toid  itself,  or  the  thyroid  plus  the  small  internal  pair  of 
parathyroids,  was  extirpated,  the  condition  called  cachexia 
strumipriva  was  observed  to  supervene.  The  symptoms  resemble 
those  of  the  disease  known  as  myxoedema,  in  which  the  charac- 
teristic anatomical  change  is  an  increase  (a  hyperplasia)  of  the 
connective  tissue  in  and  under  the  true  skin.  Newly-formed  connec- 
tive tissue  always  contains  an  excess  of  mucoids,  and  for  this  reason 
in  the  early  stages  of  myxoedema  there  is  somewhat  more  than  the 
usual  amount  of  these  substances  in  the  subcutaneous  tissue.  The 
skin  is  dry,  and  the  hair  falls  off.  The  features  are  swollen  and 
heavy,  the  movements  clumsy  and  trembling.  As  the  disease 
progresses  the  mental  powers  deteriorate  too;  the  patient  becomes 
stupid  and  slow,  and  perhaps,  at  last,  imbecile.  When  the  gland 
is  so  affected  in  early  life  that  extensive  atrophy  of  the  true  secreting 
tissue  occurs,  a  pecuHar  condition  of  idiocy  (cretinism)  results. 

In  animals  there  is  a  great  difference  in  the  results  of  total  ex- 
cision of  the  thyroids,  both  between  different  groups  and  between 
different  individuals  of  the  same  group.  In  young  animals  the 
symptoms  come  on  more  rapidly  and  are  more  severe  than  in  old. 
Monkeys  develop  symptoms  resembhng  those  of  myxoedema. 

The  older  descriptions  of  the  very  acute  onset  of  the  symptoms 
and  the  quickly  fatal  result  in  carnivorous  animals  were  vitiated 
by  the  circumstance  that,  for  the  anatomical  reason  already  alluded 
to,  the  parathyroids  were  also  involved  in  the  operation.      Never- 


654  INTERNAL  SECRETION 

theless,  the  consequences  of  complete  removal  of  the  thj^oid  proper 
are  in  general  more  serious  in  the  carnivora  than  in  the  herbivora. 
Muscular  weakness  soon  becomes  marked;  the  tissues  waste,  the 
temperature  becomes  subnormal,  and  this  is  associated  with  changes 
in  the  heat  regulation  (p.  673).  If  a  portion  of  the  th}Toid  be 
left,  or  a  graft  be  made  of  some  thyroid  tissue  from  an  animal  of 
the  same  species,  these  effects  are  entirely  obviated  so  long  as  the 
graft  survives.  It  has  not  been  established  that  a  hetero-thyroid 
graft — i.e.,  a  graft  of  th}'Toid  tissue  from  an  animal  of  a  different 
kind — even  temporarily  succeeds.  The  ahen  thyroid  cells  are 
destroyed  by  cytolysins  (p.  31)  in  the  serum  and  tissue  liquids  of 
the  animal.  When  a  small  part  of  a  thyroid  is  left,  it  may  undergo 
great  hypertrophy,  and  the  same  is  true  of  the  accessory  thyroids. 
The  administration  of  extracts  of  the  thyroid  glands  or  the  glands 
themselves  by  the  mouth  brings  about  a  cure,  permanent  so  long  as 
the  thyroid  treatment  is  continued,  in  cases  of  myxoedema  in  man, 
and  prevents  the  development  of  the  symptoms  in  animals  or 
removes  them  when  they  have  appeared.  The  same  is  true  of  a 
compound  rich  in  iodine,  the  so-called  thyroiodin,  which  has  been 
extracted  from  the  organ.  Under  this  treatment  the  total  metab- 
oHsm,  which  in  myxoedema  is  below  the  normal,  is  markedly  in- 
creased. This  is  partly  due  to  an  increase  in  the  metabolism  of 
protein.  An  increase  in  the  destruction  of  protein  is  also  caused 
in  normal  persons  and  in  normal  animals  by  feeding  with  thyroid 
or  with  thyroid  preparations.  The  excretion  of  nitrogen,  carbon 
dioxide,  and  phosphoric  acid,  and  the  intake  of  oxygen,  are  aug- 
mented. But  in  spite  of  increased  appetite  the  body-weight  falls 
off,  and  diarrhoea  is  often  caused.  For  these  reasons  the  use  of 
thyroid  preparations  to  reduce  weight  in  cases  of  obesity,  without 
evidence  of  thyroid  insufficiency,  is  a  dangerous  remedy.  For  while 
a  fat  man  can  very  well  spare  a  great  deal  of  his  fat,  he  cannot 
spare  much  of  his  tissue-protein.  That  the  gland  exerts  in  some 
way  an  important  influence  on  the  metabolism  of  proteins  is  also 
indicated  by  other  facts.  The  question  whether  the  thyroid  or 
parathyroid  is,  in  addition,  concerned  in  the  carbo-hydrate  metab- 
ohsm  is  at  present  the  subject  of  .discussion,  but  the  data  are 
so  contradictory  that  it  would  not  be  advisable  to  enter  into  the 
matter  here. 

The  ready  response  of  the  thyroid  by  hyperplasia  or  involution 
to  changes  in  the  nutritive  conditions  is  one  of  its  most  striking 
characteristics,  and  further  illustrates  the  significant  role  which  it 
plays  in  the  chemical  activities  of  the  body.  The  thyroid  swells 
and  shrinks  almost  as  easily  and  under  almost  as  great  a  variety 
of  conditions  as  the  spleen.  One  of  the  most  interesting  of  the 
physiological  changes  is  the  hyperplasia  of  the  gland  which  is  a 
normal  accompaniment  of  pregnancy.     A  pathological  change  of 


THYROIDS  AND  PARATHYROIDS 


635 


great  interest,  because  of  the  careful  manner  in  which  it  has  been 
studied,  is  the  endemic  goitre  (sometimes  erroneously  termed  *  car- 
cinoma ')  of  brook  trout  kept  under  artificial  conditions  in 
hatcheries.  Marine  has  shown  that  this  depends  upon  overfeeding 
with  unsuitable  food  (such  as  livers  of  cattle,  pigs,  or  sheep),  over- 
crowding, and  insufficiency  of  water-supply,  and  that  the  goitre 
can  be  readily  cured  or  prevented  by  changing  the  conditions  in 
these  respects.  Similar  results  have  been  obtained  in  mammals  fed 
exclusively  with  meat.  Thus,  lion  cubs  at  the  Zoological  Gardens 
in  London  on  a  diet  consisting  only  of  raw  meat  developed  rickets 
and  goitre,  as  did  puppies  fed  with  meat,  lungs,  liver,  or  heart,  and 
nothing  else;  whereas  when  milk,  bread,  and  bone  were  added  to 
meat  the  puppies  grew  nor- 
mally (Marine).  A  meat  diet 
caused  hyperplasia  of  the 
thyroid  in  rats  (Chalmers 
Watson).  The  relation  of  the 
disease  known  as  exophthal- 
mic goitre  to  the  thyroid 
has  been  much  debated.  The 
best  evidence  is  against  the 
hypothesis  that  the  symp- 
toms are  due  to  increased 
activity  of  the  thyroid  func- 
tion (so-called  hyperthyroid- 
ism). All  attempts  to  pro- 
duce anything  resembling 
the  pathological  condition  by 
the  administration  of  large 
amounts  of  th3'roid  or  of 
thyroid  products  have  failed. 
Nor  has  it  ever  been  shown 
that  the  changes  in  the  gland 
are  the  primary  cause  of  the 

syndrome.  Indeed,  no  specific  anatomical  or  chemical  changes 
have  as  yet  been  demonstrated  in  the  thyroid  in  this  condition. 
The  thyroid  gland  of  exophthalmic  goitre  has  the  same  action  on 
animals  and  on  patients  suffering  from  exophthalmic  goitre  as  any 
other  thyroid  gland  with  like  iodine  content  (Marine). 

The  relations  of  iodine  to  the  gland  itself,  and  the  modifications 
in  its  structure  and  function  determined  by  the  giving  or  withholding 
of  iodine,  recently  studied  by  Marine,  are  of  great  interest.  In  all 
animals,  so  far  as  examined,  the  normal  thyroid  contains  iodine. 
The  amount  is  variable,  but  the  minimum  percentage  of  iodine 
necessary,  if  the  normal  histological  structure  is  to  be  maintained, 
is  quite  constant  for  a  given  species.     So  also  the  highest  percentage 


Fig.  203. — Microphotograph  of  Active  Th>Toid 
Hv^perplasia  from  a  Case  of  Exophthalmic 
Goitre  (Marine).  The  characteristic  changes 
in  the  hyperplastic  gland — the  infoldings 
and  plications  of  the  alveolar  epithelium, 
the  great  reduction  in  the  colloid,  and  the 
increase  in  the  stroma — are  shown. 


636 


INTERNAL  SECRETION 


Fig.  204. — Microphutograph  of  a  Colloid 
Gland  (Goitre)  (Marine).  The  effect  of  ad- 
ministration of  iodine  is  shown  in  the  return 
towards  the  normal  structure  from  a  pre- 
ceding active  hyperplasia,  such  as  is  shown 
in  Fig.  203. 


of  iodine  associated  with  any  degree  of  active  hyperplasia  (develop- 
ing goitre)  is  always  below  the  normal  minimum,  as  shown  by 

Marine  in  the  dog,  sheep, 
man,  and  other  mammals. 
As  active  hyperplasia  of  the 
thyroid  (goitre)  (Fig.  203) 
develops,  the  iodine  content 
of  the  gland,  both  relative 
and  absolute,  decreases,  until 
in  extreme  degrees  of  the 
condition  there  may  be  no 
demonstrable  iodine  present 
at  all.  Since  the  iodine  is 
contained  in  the  colloid  as 
an  iodine-protein  compound, 
the  generalization  may  be 
made  that  in  the  thyroid  the 
iodine  varies  directly  with 
the  amount  of  colloid,  and 
inversely  with  the  degree  of 
hyperplasia.  The  administra- 
tion of  any  iodine-containing 
substance  to  animals  with 
actively  hyperplastic  thyroids  (goitres)  quickly  (in  two  to  three 
weeks  in  dogs)  induces  a  histological  change,  the  end  stage  of  which 
is  the  so-called  colloid  goitre  (Fig.  204).  This  is  a  reversion  to 
the  normal  histological  struc- 
ture (Fig.  205),  so  far  as  this 
is  possible  in  a  gland  which 
has  once  undergone  hyper- 
plasia. The  physiological 
influence  of  iodine  on  the 
thyroid  may  be  summed  up 
as  follows  :  Iodine  is  abso- 
lutely essential  for  the  normal 
activity  of  the  gland.  It 
prevents  spontaneous  hyper- 
plasia (goitre),  and  also  the 
compensatory  hyperplasia 
which  follows  partial  re- 
moval of  the  thyroid.  It 
exercises  a  curative  effect 
on  active  hyperplasias.  The 
physiological  and  therapeu- 
tical activity  of  thyroid  substance  vaiies  directly  with  the  amount 
of  iodine  in  it  in  organic  combination  (thyroiodin). 


Fia. 


205. — Microphotograph    of    Normal 
Human  Thyroid  (Marine). 


ADRENALS  6^7 

As  in  the  case  of  other  glands  forming  an  internal  secretion,  it 
has  been  debated  whether  the  function  of  the  thyroid  is  to  destroy 
toxic  bodies  or  to  form  substances  indispensable  or  advantageous 
to  the  organism.  Wliile  the  precise  role  played  by  the  organ  in  the 
economy  remains  obscure,  it  is  evident  that  in  most  animals  and  in 
man  its  secretion  is  of  great  importance,  whether  it  be  solely  the 
quasi-external  secretion  of  '  colloid,'  containing  the  thyroiodin,  that 
collects  in  its  alveoli  and  slowly  passes  out  of  them  by  the  lym- 
phatics, or  perhaps,  in  addition,  some  other  substance,  which,  like 
the  glycogen  of  the  liver,  never  finds  its  way  into  the  lumen  of  the 
gland-tubes  at  all.  It  may  also  be  admitted  that,  by  aiding  in  the 
maintenance  of  the  normal  level  of  general  nutrition,  particularly 
that  of  the  central  nervous  system,  the  ability  of  the  organism  to 
cope  with  toxic  substances  introduced  from  the  outside  or  manu- 
factured in  the  bod}^  is  favoured.  There  is,  however,  no  evidence 
that  an  actual  destruction  or  neutralization  of  toxic  substances 
occurs  in  the  gland  itself. 

It  is  probable  that  the  secretion  of  the  thyroid  is  influenced  by 
nerves.  Section  of  the  superior  and  inferior  thyroid  nerves  going 
to  the  gland  is  followed  by  degenerative  changes  in  it.  It  has  been 
stated  that  stimulation  in  the  dog  of  the  nerves  entering  one  thyroid 
lobe  on  the  bloodvessels,  or  of  the  cephalic  end  of  the  vago-sympa- 
thetic  nerve  below  the  superior  cervical  ganghon,  causes  a  diminu- 
tion in  the  iodine  content  of  that  lobe  as  compared  with  the  other 
(Fawcett  and  Beebe).  This  result  has  been  interpreted  as  due  to  the 
excitation  of  fibres  which  accelerate  the  passage  of  the  active 
substance  out  of  the  gland.  It  has  long  been  known  that  vaso- 
motor fibres  for  the  dog's  thyroid  run  up  in  the  cervical  sympathetic 
to  the  superior  cervical  ganghon,  and  thence  to  the  lobe  of  the 
same  side.  These  were  first  discovered  by  the  effect  produced  by 
their  stimulation  on  the  thyroid  circulation  time  (p.  135).  Further 
evidence  of  the  existence  of  secretory  fibres  has  iDeen  brought  for- 
ward by  Asher  and  Flack.  They  compared  the  excitability  of  the 
depressor  nerve,  and  also  the  effect  on  the  blood-pressure  of  the 
intravenous  injection  of  adrenalin,  before  and  during  stimulation 
of  the  thyroid  nerves.  They  conclude  that,  when  all  the  other 
conditions  remain  unchanged,  both  the  effect  of  excitation  of  the 
depressor  and  the  effect  of  adrenalin  are  greater  during  stimulation 
of  the  thyroid  nerves  than  shortly  before  it  without  such  stimula- 
tion. The  difference  is  really  connected  with  the  internal  secretion 
of  the  thyroid,  since  it  is  not  obtained  if  the  thyroids  are  previously 
extirpated,  and  injection  of  thyroid- extracts  influences  the  result 
exactly  in  the  same  way  as  stimulation  of  the  thyroid  nerves. 

Adrenal  Bodies. — It  had  been  observed  by  Addison  that  the 
malady  which  now  bears  his  name,  and  in  which  certain  vascular 
changes,  with  muscular  weakness,  anaemia,  and  pigmentation  or 


638  INTERNAL  SECRETION 

'  bronzing  '  of  the  skin,  are  prominent  symptoms,  was  associated 
with  disease,  usually  tuberculous,  of  the  adrenal  bodies,  commonly 
called  in  human  anatomy  the  '  suprarenal  capsules.'     This  clinical 
result  was  soon  supplemented  by  the  discovery  that  extirpation  of 
the  adrenals  in  animals  is  incompatible  with  life  (Brown-Sequard). 
Our  knowledge  of  the  functions  of  these  hitherto  enigmatic  organs 
was  extended  by  the  experiments  of  Oliver  and  Schafer,  who  in- 
vestigated the  action  of  extracts  of  the  adrenals  (of  calf,  sheep, 
dog,  guinea-pig,  and  man)  when  injected  into  the  veins  of  animals. 
The  arteries  are  greatly  contracted,  and  this  mainly  through  direct 
action  on  the  vaso-motor  nerve-endings  or  some  structure  inter- 
mediate between  them  and  the  smooth  muscle  of  the  vessels,  but 
partly  through  the  vaso-motor  centre.     The  blood-pressure  rises 
rapidly,  although  the  heart  may  be  inhibited  through  the  vagus 
centre.     The  heart  is  at  the  same  time  directly  stimulated,  so  that, 
although  it  beats  slowly,  the  beats  are  stronger  than  before.     When 
the  vagi  are  cut  the  action  of  the  heart  is  markedly  augmented, 
and  the  arterial  pressure  rises  enormously  (it  may  be  to  four  or  five 
times  its  original  amount).     Stimulation  of  the  depressor  is  of  no 
avail  in  combating  this  increase  of  blood-pressure.     The  generaliza- 
tion may  be  made  that  suprarenal  extract  or  adrenalin — also  called 
'  epinephrin  '  and  '  suprarenin ' — ^its  active  principle,  acts  upon  all 
plain  muscle  and  gland-cells  that  are  supplied  with  sympathetic 
nerve- fibres,  and  the  result  of  the  action,  whether  augmentation 
or  inhibition,  is  the  same  as  would  be  produced  by  stimulation  of 
the  sympathetic  fibres  going  to  the  muscle  or  gland  in  question. 
Yet  it  is  not  through  excitation  of  these  fibres  that  the  adrenalin 
acts,  for  its  effect  is  even  more  pronounced  when  the  nerve-fibres 
have  been  caused  to  degenerate,  in  the  case  of  the  pupillo-dilator 
fibres,  e.g.,  by  excision  of  the  superior  cervical  ganglion.     Nor  is  the 
effect  a  direct  one  on  the  muscular  fibres.     For  smooth  muscle  which 
is  not,  and  never  has  been,  in  functional  union  with  sympathetic 
nerve- fibres  is  indifferent  to  adrenaUn  (Elliott).     It  seems,  then, 
to  act  on  some  structure  intermediate  between  the  nerve  and  the 
muscle,  but  so  related  to  the  latter  that  it  continues  to  live  so  long 
as  it  is  in  connection  with  the  muscle-fibre.     Instead  of  a  definite 
histological  structure,  the  seat  of  the  action  may  be  a  special  '  re- 
ceptive '  substance  at  the  myoneural  junction.     Thus  adrenalin 
causes  marked  diminution  of  tone  in  the  small  intestine,  with  dis- 
appearance of  the  peristalsis  and  pendulum  movements.     The  same 
effect  is  produced  on  an  isolated  loop  of  intestine  immersed  in 
Locke's  solution,  and  the  action  is  therefore  local.     The  drug  is , 
effective  in  a  dilution  of  i :  1,000,000,  or  even  in  much  greater  dilution. 
A  similar  effect  has  been  observed  on  the  stomach.     The  vessels 
of  the  conjunctiva  are  constricted  by  local  action  when  an  extract 
of  the  capsules  is  dropped  into  the  eye,  a  fact  which  has  proved  of 


ADRENALS  639 

value  in  ophthalmologicai  practice.  Inhibition  of  the  contraction 
of  the  stomach,  intestine,  urinary  bladder,  and  gall-bladder;  con- 
traction of  the  uterus,  vas  deferens,  and  seminal  vesicles;  dilatation 
of  the  pupil  and  retraction  of  the  nictitating  membrane ;  stimulation 
of  the  salivary  and  lachrymal  secretions,  are  among  its  actions 
(Langley).  The  curve  of  contraction  of  the  skeletal  muscles  is 
lengthened  as  in  veratrine  poisoning  (p.  729),  though  to  a  less  extent. 

Meltzer  has  shown  that  the  dilatation  of  the  pupil  caused  by 
the  intravenous  injection  of  adrenalin  is  distinct,  though  fleeting,  in 
cats,  less  marked  in  rabbits.  Subcutaneous  injection  has  no  effect. 
Instillation  of  the  drug  into  the  conjunctival  sac  is  without  effect 
on  the  pupil  in  the  normal  rabbit's  eye,  but  causes  dilatation  if  the 
superior  cervical  ganglion  has  been  removed. 

The  influence  of  adrenalin  in  increasing  the  sugar  content  of  the 
blood,  and  thus  causing  glycosuria,  has  been  previously  discussed 
(p.  541).  A  new  and  interesting  action  has  recently  been  added 
by  Cannon  to  the  already  long  list  of  the  effects  of  adrenalin,  by  the 
discovery  that  small  doses  (o-ooi  milligramme  per  kilo  of  body- 
weight)  and  larger  doses  injected  subcutaneously  into  cats  shorten 
the  coagulation  time  of  the  blood  to  one-half  or  one-third  of  its 
previous  duration,  probably  by  stimulating  the  liver  to  greater 
activity  in  discharging  some  substance  or  substances  concerned  in 
clotting. 

Methods  for  the  detection  and  the  assay  of  adrenahn  in  the  small 
quantities  in  which  it  can  only  be  supposed  to  be  present  in  physio- 
logical liquids  have  been  based  upon  certain  of  these  actions.  Such, 
for  example,  is  the  extraordinary  power  of  this  active  principle 
that  a  dose  of  one-millionth  of  a  gramme  per  kilo  of  body-weight  is 
sufficient  to  cause  a  distinct  effect  upon  the  heart  and  bloodvessels 
(a  rise  of  pressure  of  14  millimetres  Hg)  when  it  is  injected  into 
the  veins  of  a  mammal.  The  reaction  is  rendered  more  constant, 
although  less  delicate,  when  the  brain  is  previously  destroyed  and 
the  animal  used  as  a  spinal  preparation.  In  pithed  cats  the  assay 
can  be  accurately  performed  to  001  milligramme.  Another  delicate, 
and  for  certain  purposes  a  convenient,  reaction  for  the  detection 
and  the  physiological  assay  of  adrenahn  is  the  perfusion  test  on  the 
legs  of  frogs  already  alluded  to  (p.  46).  The  dilatation  of  the  pupil 
in  the  excised  eyeball  of  the  frog,  the  contraction  of  stretched 
artery  rings  (p.  66),  the  increase  in  the  tone  of  isolated  segments 
of  the  uterus  of  rabbits  or  guinea-pigs,  and  the  diminution  in  the 
tone  of  isolated  segments  of  intestine  (Practical  Exercises,  p.  447), 
have  also  been  employed  as  physiological  tests. 

A  dilute  solution  of  adrenalin  chloride  is  used  in  medicine  as 
a  styptic,  and  for  reducing  congestion  in  accessible  parts.  The 
intense  local  anaemia  which  it  causes  when  given  subcutaneously 
or  by  the  mouth  is  one  reason,  perhaps  the  most  important,  for  the 


640  INTERNAL  SECRETION 

slow  absorption  on  which  depends  the  absence  of  its  general  effects, 
including  that  on  the  blood-pressure,  when  it  is  administered  in 
this  way. 

Function  of  Epinephrin  (or  Adrenalin). — The  striking  effects 
produced  by  adrenalin  have  naturally  led  to  the  assumption  that 
its  function  in  the  bodj'  must  be  important.  It  has  been  con- 
clusively proved  that  under  certain  conditions  it  is  given  off  to  the 
blood,  but  only  in  such  quantities  as,  when  diluted  by  the  general 
ma^s  of  the  blood,  lie  far  below  the  concentration  necessary  for  detec- 
tion by  any  of  the  biological  methods  mentioned  above.  In  fact,  no 
proof  has  ever  been  given  that  in  blood  withdrawn  from  an  artery, 
either  in  health  or  disease,  adrenalin  exists  at  all.  When  the 
adrenal  gland  of  a  dog  is  directly  massaged  by  the  fingers,  the  blood 
coming  from  the  adrenal  vein  has  been  shown  to  contain  a  small 
but  detectable  amount  of  adrenaUn.  The  same  is  true  of  the  blood 
coming  from  the  adrenal  during  stimulation  of  the  splanchnic 
nerves  on  the  corresponding  side  (Fig.  206). 

The  existence  of  secretory  fibres  for  the  adrenal  glands  in  the 
splanchnic  nerves  was  first  indicated  by  the  experiments  of  Dreyer, 
who  found  that  the  amount  of  active  substance  in  the  blood  of  the 
suprarenal  vein,  as  tested  by  its  physiological  effect  when  injected 
into  an  animal,  was  increased  by  stimulation  of  those  nerves. 

Under  the  influence  of  strong  emotions,  painful  stimulation  of 
sensory  nerves,  and  other  conditions,  the  quantity  of  adrenalin 
which  can  be  extracted  from  the  adrenals  is  markedly  diminished, 
but  not  if  the  splanchnic  fibres  have  been  previously  cut. 

That  adrenahn  is  actually  given  off  to  the  blood  during  stimula- 
tion of  a  nervous  mechanism  of  which  the  efferent  fibres  run  in  the 
splanchnics  is  further  indicated  by  facts  Uke  the  following:  Similar 
changes  in  the  clotting  time  of  blood  are  produced  by  splanchnic 
stimulation  as  by  injection  of  adrenalin,  and  these  changes  do  not 
occur  if  the  adrenal  on  the  side  of  the  stimulated  nerve  has  been 
previously  excised.  Excitation  of  afferent  nerves  under  light 
anaesthesia  and  emotional  excitement  also  shorten  the  coagulation 
time,  but  this  effect  is  not  obtained  after  section  of  the  splanchnic 
nerves.  Temporary  improvement  in  the  response  to  stimulation 
of  a  fatigued  muscle,  still  in  connection  with  the  circulation,  is 
observed  on  excitation  of  the  splanchnic  nerve  if  the  corresponding 
adrenal  is  intact,  and  a  similar  reaction  is  obtained  on  injection 
of  epinephrin. 

The  existence  of  a  reflex  nervous  mechanism  through  which  the 
gland  can  be  stimulated  to  secrete  adrenalin  into  the  blood  can 
therefore  be  considered  as  definitely  established.  But  the  function 
of  the  adrenalin,  once  it  has  entered  the  circulation,  is  involved  in 
doubt.  The  common  view  is  that  it  exerts  an  important  physiological 
action  upon  the  sympathetic  system,  contributing  especially  to  the 


ADRENALS 


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642  INTERNAL  SECRETION 

maintenance  of  the  normal  vaso-motor  tone,  and  therefore  to  the 
maintenance  of  the  normal  blood-pressure.  All  the  best  evidence 
is  against  this  view.  Whatever  influence  the  relatively  small 
quantities  of  adrenaUn  discharged  from  time  to  time  may  have  upon 
the  nutrition  of  the  smooth  or  of  other  muscles,  it  is  quite  unlikely 
that  such  amounts  are  continuously  entering  the  blood  as  injection 
experiments  have  shown  to  be  necessary  for  the  maintenance  of  even 
a  small  excess  of  blood-pressure.  Statements  which  connect  the 
increased  blood-pressure  in  such  conditions  as  chronic  nephritis  with 
hypertrophy  of  the  chromaffin  tissue  (p.  643),  an  increased  adrenalin 
production,  and  an  increased  adrenalin  content  of  the  blood,  must 
be  received  with  scepticism.  The  so-called  experimental  arterio- 
sclerosis produced  by  repeated  injections  of  adrenalin  into  the 
blood  of  rabbits  throws  little  hght  upon  the  question,  for  the 
vascular  changes,  in  so  far  as  they  have  not  been  confounded  with 
similar  lesions  occurring  spontaneously  in  a  considerable  proportion 
of  rabbits,  differ  from  those  observed  in  pathological  arterio- 
sclerosis (M.  C.  Hill). 

Certain  facts  indicate,  indeed,  that  doses  of  adrenalin  considerably 
smaller  than  those  which  give  the  effects  described  above,  and 
usually  considered  the  '  normal '  effects,  produce  a  reversal  of  the 
reaction,  very  small  doses  causing,  for  instance,  a  diminution  of 
blood-pressure  (Moore  and  Purington),  an  increase  in  intestinal 
tonus  and  peristalsis,  and  a  diminution  in  the  tone  of  uterine  seg- 
ments. The  actions  associated  with  these  small  doses  are  more 
likely  to  be  the  normal  actions  than  those  associated  with  the 
larger  doses,  and  the  normal  action  of  adrenalin,  if  it  is  a  continuous 
action,  would  therefore  more  probably  be  to  inhibit  than  to  excite 
the  sympathetic  mechanism.  But  there  is  no  evidence  that  even 
quantities  of  this  order  of  magnitude  are  continuously  discharged. 
The  continuous  introduction  of  epinephrin  at  a  very  slow  rate 
produces  no  demonstrable  effect  at  all,  and  the  sudden  ligation  of 
all  the  adrenal  bloodvessels  has  not  the  slightest  influence  upon 
the  blood-pressure  until  the  lapse  of  a  period  far  greater  than  would 
be  required  for  the  destruction  or  removal — a  quite  rapid  process — 
of  any  epinephrin  already  present  in  the  blood  or  tissues  (Tren- 
delenburg, Hoskins).  The  injection  of  a  quantity  of  adrenalin 
sufficient  to  cause  and  to  long  sustain  even  a  minimal  increase  of 
blood-pressure  creates  conditions  highly  hazardous  to  life  or  in 
compatible  with  it — namely,  complete  paralysis  of  the  gastro- 
intestinal tract. 

The  suggestion  that  enough  epinephrin  may  be  continuously 
Hberated  to  exert  an  influence  upon  the  nutrition  and  metabolism 
of  the  sympathetic  system,  or  of  the  myoneural  junction,  which  is 
necessary  for  normal  excitability,  without  ever  rising  to  the  thres- 
hold of  actual  excitation,  is  a  mere  hypothesis,  and  a  hypothesis 


ADRENALS  643 

which  does  not  seem  easily  reconciled  with  the  result  of  Hoskins, 
that  after  ligation  of  the  adrenals  the  excitability  of  the  vaso-motors 
remains  absolutely  undiminished. 

So  far  as  our  present  data  go,  the  function  of  the  adrenal  bodies 
— at  least  that  part  of  their  function  which  is  concerned  with  the 
liberation  of  adrenalin — is  not  to  be  considered  a  continuous,  but 
an  emergency  function  (Cannon),  exerted  at  times  of  physical  or 
emotional  stress.  It  has  been  pointed  out,  and  with  much 
plausibility,  that  a  rapid  discharge  of  such  large  quantities  of 
adrenahn  as  could  really  produce  distinct  physiological  effects 
would  be  advantageous  in  such  emergencies.  The  increased 
mobilization  of  sugar,  for  example,  the  increased  action  of  the 
heart  muscle,  and  the  shortened  clotting  time  of  the  blood 
occasioned  by  the  outpouring  of  adrenahn  in  response  to  the 
accompanying  excitement  of  fear  or  rage  or  pain  might  be  helpful 
in  a  struggle  associated  with  trauma.  And  as  evolution  has 
been  so  closely  connected  with  physical  struggle,  an  adaptive 
mechanism  of  this  sort  may  have  been  developed. 

Chemistry  and  Formation  of  Adrenalin. — It  has  been  shown  (Stolz, 
Dakin)  that  adrenahn  (C9H13NO3)  is  a  dioxyphenyl-ethanol-methylamin, 

CH 
OH.C/\C.CH  (OH)  .CH2NH  .CH3 

OH.C        CH 

CH 

It  has  been  prepared  synthetically,  and  in  the  body  appears  to  be 
formed,  probably  by  the  introduction  of  a  methyl  (CH3)  group,  from 
a  compound  arising  from  an  aromatic  amino-acid  (tyrosin  or  phenyl- 
alanin).  While  the  natural  adrenalin  rotates  the  plane  of  polarization 
to  the  left,  the  artificial  substance  is  optically  inactive.  This  is  because 
it  consists  of  equal  parts  of  laevo-rotatory  and  dex±ro-rotatory  adrenalin. 
The  artificial  adrenalin  has  approximately  half  the  effect  of  the  natural 
on  the  blood-pressure,  from  which  it  may  be  inferred  that  the  dextro- 
rotatory isomer  has  only  a  very  slight  pressor  effect.  The  left  and  right 
rotatory  moieties  have  been  separated.  The  former  has  exactly  the 
same  power  of  raising  the  blood-pressure  as  the  natural  adrenalin,  the 
latter  only  ji„  to  ^^  as  much.  Practically  the  same  proportion  holds 
when  the  power  of  the  two  isomers  in  producing  glycosuria  is  compared. 
This  constitutes  important  corroboration  of  the  view  already  referred 
to  (p.  542),  that  adrenalin  glycosuria  is  caused  by  an  action  on  the 
sympathetic  system,  for  the  effect  on  the  blood  -  pressure  is  known 
to  be  thus  produced  (Cushny). 

It  is  in  the  medulla  of  the  adrenals  that  the  epinephrin  is  formed. 
The  medullary  cells  contain  a  substance  which  gives  a  yellow  or  brown 
stain  with  chromic  acid  or  chromates,  and  for  this  reason  the  cells  are 
called  chromaffin  or  chromaphil.  Similar  cells  are  found  elsewher-e  in 
tlie  body — e.g.,  within  the  sympathetic  gaHglia,  and  also  strung  out 
in  clunips  along  the  course  of  the  abdominal  aorta  below  the  level  of 
the  adrenal  glands  (Vincent).  These  outlying  masses  of  clwomaffin 
tissue  appear  to  contain  epinephrin,  or  a  substance  with  similar  physi- 


644  INTERNAL  SECRETION 

ological  actions,  so  that  the  formation  of  this  compound  seems  to  be  a 
property  common  to  chromaphil  tissue,  no  matter  wliat  its  situation 
may  be.  A  remarkable  fact,  and  one  calculated  to  induce  caution 
in  assigning  a  physiological  function  to  epinephrin,  is  that  the  so-called 
parotid  gland  of  a  Jamaican  toad  secretes  it  in  a  concentration  not 
much  short  of  5  per  cent.  (Abel). 

Function  of  the  Adrenal  Cortex. — The  function  of  the  cortical 
cells  is  very  obscure,  but  there  is  some  evidence  that  they,  and  not 
the  chromaffin  cells  of  the  medulla,  are  concerned  in  the  production 
of  the  internal  secretion,  whatever  its  nature  may  be,  the  loss  of 
which  leads  so  speedily  to  death  on  removal  of  the  adrenals  or  in 
the  neutralization  of  poisonous  products  if  that  is  the  essential 
thing.  For  example,  the  period  of  survival  after  this  operation  is 
practically  unaffected  by  the  continuous  intravenous  adminis- 
tration of  adrenaUn,  although  the  loss  of  the  medulla  might  be 
supposed  to  be  compensated  in  this  way.  In  Addison's  disease 
adrenalin  is  likewise  powerless.  When  the  adrenals  are  not  com- 
pletely extirpated,  compensatory  hypertrophy  of  the  remaining 
portions  may  occur,  and  the  animal  survive  indefinitely.  In  such 
cases  it  has  been  found  that  the  hypertrophy  is  confined  to  the 
cortex.  The  weakness  (asthenia)  of  the  skeletal,  and  to  some 
extent  of  the  cardiac,  musculature  which  is  characteristic  of  Addi- 
son's disease,  is  produced  experimentally  within  a  few  hours  by 
ligation  of  both  adrenals.  It  is  stated  that  the  cortex  contains 
cholin,  a  substance  which  lowers  the  blood-pressure,  instead  of 
raising  it,  as  adrenaUn  does.  It  has  been  suggested  that  the  adrenal 
glands  have  thus  a  double  chemical  grip  upon  the  circulation,  and 
can  influence  it  in  either  direction,  just  as  the  bulb  can  influence  it 
through  its  double  nervous  grip.  But  it  is  possible  that  the  depres- 
sor substance  of  the  cortex  may  be  only  a  toxic  body  neutralized 
or  destroyed  in  the  glands.  In  any  case  the  functional  difference 
between  cortex  and  medulla  is  easily  understood  when  we  reflect 
that  the  morphological  history  of  the  two  tissues  is  quite  different. 
The  medulla  is  developed  from  cells  which  push  their  way  into  the 
gland  from  the  rudiments  of  the  sympathetic  ganglia  at  that  level, 
and  is  therefore  of  ectodermic  origin.  The  cortex  is  derived  from 
the  same  mesodermic  structure  which  gives  rise  to  the  kidneys  and 
genital  organs. 

Pituitary  Body  or  Hypophysis. — In  the  pituitary  body  two  parts 
essentially  different  in  origin  and  function  may  be  distinguished: 
(i)  The  large  anterior  lobe,  or  pars  anterior,  consisting  of  epithelial 
cells,  many  of  which  are  filled  with  granules  of  the  type  seen  in 
glandular  epithelium,  and  abundantly  provided  with  bloodvessels; 
(2)  the  smaller  posterior  or  nervous  lobe,  or  pars  nervosa,  also 
called  the  infundibular  portion,  consisting  chiefly  of  neuroglia,  the 
whole  connected  with  the  floor  of  the  third  ventricle  by  a  stalk 
called  the  infundibulum. 


PITUITARY  BODY  645 

A  further  subdiv^ision  of  the  epithelial  portion  is  made  into  the 
anterior  lobe  proper  and  tlie  pars  intermedia  or  intermediate  lobe,  con- 
sisting of  epithelial  cells,  less  granular  and  less  richly  supplied  with 
bloodvessels  than  those  of  the  pars  anterior.  The  pars  intermedia 
forms  an  epithelial  investment  of  the  pars  nervosa,  almost  completely 
surrounding  it  and  throwing  out  offshoots  of  epithelial  cells  into  its 
substance,  which  is  also  invaded  by  colloid  material  secreted  by  the 
cells  of  the  intermediate  lobe.  The  differences  in  the  structure  of  the 
anterior  and  posterior  lobes  of  the  pituitary  body  correspond  to  a 
difference  in  their  development.  The  anterior  lobe  is  developed  (in 
man  in  the  fourth  week  of  intra-uterine  life)  from  an  ectodermal  pouch 
(Rathke's  pouch),  which  is  pushed  up  from  the  roof  of  the  bucco- 
phar^mgeal  cavity  towards  the  mid-brain.  The  posterior  lobe  is 
developed  from  an  extension  of  the  neural  ectoderm,  which  grows  back- 
wards as  the  infundibular  process  till  it  meets  and  blends  with  that 
portion  of  the  buccal  pouch  which  gives  rise  to  the  pars  intermedia. 
The  pars  intermedia  is  separated  from  the  anterior  lobe  proper  by  a 
cleft  which  represents  what  is  left  of  the  lumen  of  Rathke's  pouch. 
In  connection  with  the  interpretation  of  the  results  of  experiments  on 
removal  of  the  pituitar}^  body,  it  is  of  consequence  to  remember  that 
a  residue  of  the  same  epithelium  which  develops  into  the  anterior  lobe 
appears  always  to  get  cut  off  in  the  vault  of  the  pharynx,  constituting 
the  so-called  pharyngeal  hypophysis,  and  consisting  of  a  cord  of  cells 
identical  with  those  of  the  anterior  lobe  (Haberfeld).  Embryonic 
'  rests  '  of  hypophyseal  tissue  are  also  often  found  in  the  dura  of  the 
sella  turcica,  in  which  the  pituitary  body  lies,  and  in  the  body  of  the 
sphenoid  bone.  Cells  of  the  intermediate  lobe  also  run  up  the  stalk 
of  the  infundibulum,  and  even  stretch  for  a  little  distance  along  the 
floor  of  the  third  ventricle.  Add  to  this  the  formidable  nature  of  the 
operations  required  for  the  extirpation  of  the  hypophysis  from  its 
sheltered  position  within  the  skull,  and  it  will  not  be  wondered  at  that 
complete  harmony  has  not  been  attained  as  to  the  consequences  of  its 
removal.     The  best  evidence  at  present  is  to  the  following  effect: 

When  the  pituitary  body  is  completely  removed,  death  speedily 
and  invariably  ensues,  in  dogs,  on  the  average  witliin  twenty-four 
to  forty-eight  hours.  Puppies  often  live  as  long  as  two  or  three 
weeks.  The  much  longer  periods  of  survival  occasionally  witnessed 
are  due  to  failure  to  remove  some  small  portion  of  the  hypophyseal 
epithelium.  On  the  day  after  the  operation  the  animals  may  be 
able  to  walk  about,  to  eat  and  drink,  and  may  show  an  interest  in 
their  surroundings.  The  temperature,  pulse,  and  respiration  at 
this  time  may  be  normal.  Soon,  however,  they  become  lethargic, 
then  comatose,  with  characteristically  incurved  spine,  slow  respira- 
tion, with  long-drawn  inspiration,  a  feeble  pulse,  perfectly  limp 
muscles,  and  often  a  subnormal  temperature,  and  the  appearance 
of  sugar  in  the  urine.  This  deep  coma  passes  into  death,  with  no 
perceptible  transition,  and  without  a  struggle  (Paulesco,  Gushing). 
The  ablation  of  a  part  of  the  cortical  substance  of  the  anterior 
(epithelial)  lobe  of  the  hypophysis  is  compatible  with  permanent 
survival,  and  gives  rise  to  no  symptom  of  disorder.  The  same  is 
true  when  only  the  posterior  lobe  is  removed.  This  docs  not  seem 
to  be  followed  by  any  recognizable  symptoms.     In  some  animals, 


646  INTERNAL  SECRETION 

however,  kept  under  observation  for  long  periods  after  partial 
removal  of  the  anterior  lobe,  a  marked  tendency  to  accumulate 
fat  has  been  noted,  accompanied  by  hypoplasia  of  the  generative 
organs  in  adults  or  the  persistence  of  the  infantile  condition  in 
immature  animals.  On  the  other  hand,  complete  removal  of  the 
anterior  lobe  causes  death,  just  as  if  the  whole  gland  had  been 
taken  away.  Of  all  the  structures  included  in  the  pituitary  body, 
the  most  important  from  the  functional  point  of  view  appears  to  be 
the  superficial  layer  of  the  anterior  lobe. 

Mere  separation  of  the  stalk  of  the  hypophysis  may  produce 
effects  sometimes  as  serious  as  those  of  total  removal  of  the  gland, 
probably  owing  to  the  disturbance  caused  in  the  circulation.  It  is 
stated,  indeed,  by  some  observers  that  the  vulnerable  point  is  the 
base  of  the  infundibulum,  and  that  if  this  is  not  injured  extirpation 


...y^' 


,^^^-wV 


Fig.  207. — Action  of  Extract  of  Hypophyseal  Lobe  of  Pituitary  on  the  Blood- Pressure 
(W.  W.  Hamburger).  The  signal  line  at  the  top  shows  the  time  and  length  of 
injection  of  the  saline  extract  into  the  blood.  Time-trace  (at  bottom)  shows 
second  intervals.     The  figure  is  to  be  read  from  left  to  right. 

of  the  hypophysis  is  not  incompatible  with  continued  existence, 
and  that  in  adult  animals  the  resultant  changes  are  only  slight, 
although  much  more  pronounced,  especially  as  regards  the  disturb- 
ances in  metabolism  and  development  in  young  animals.  It  has 
been  asserted  that  the  pituitary  undergoes  (compensatory  ?)  hyper- 
trophy after  thyroidectomy.  Some  observers  have  accordingly 
assumed  a  similarity  of  function  for  these  organs.  It  has  even  been 
stated  that  the  production  of  colloid  material  by  the  cells  of  the  pars 
intermedia  is  increaised,  and  that  colloid  accumulates  in  the 
nervous  portion  of  the  posterior  lobe.  But  this  colloid,  whatever 
its  function  may  be,  is  very  different  from  that  of  the  thyroid 
alveoli,  for  the  (sheep's)  pituitary  contains  no  iodine  after  extir- 
pation of  the  thyroid  any  more  than  before  (Simpson  and 
Hunter).  And  in  man  pathological  changes  (tumours)  in  the 
pituitary  body  are  associated,   not   with   myxoedema,    or  other 


PITUITARY  BODY  647 

disease  connected  with  changes  in  the  thyroid,  but  frequently  with 
another  condition,  called  acromegaly,  in  which  the  bones  of  the 
limbs  and  face,  especially  the  hands  and  feet  and  the  lower  jaw, 
become  hypertrophied. 

Another  condition  often  associated  with  tumours  of  the  pituitary 
is  gigantism — a  condition  occurring  before  the  normal  growth  of 
the  bones  is  completed,  and  resulting  in  a  great  increase  in  the 
length  of  the  bones  both  in  the  limbs  and  the  trunk. 

Action  of  Intravenous  Injection  of  Extracts  of  the  Pituitary. — 
The  effects  on  the  vascular  system  of  intravenous  injection  of 
extracts  of  the  pituitary  gland  are  also  very  different  from  those 
caused  by  thyroid  extracts.  The  posterior  lobe,  or  infundibular 
body,  including  the  pars  intermedia,  contains  two  active  substances, 
one  pressor  and  the  other  depressor.  The  former  is  soluble  in  salt 
solution,  but  insoluble  in  absolute  alcohol  and  ether;  while  the 
latter  is  soluble  in  sail  solution  as  well  as  in  alcohol  and  ether.  The 
pressor  substance  (obtained  in  fairly  pure  form  in  the  preparation 
called  pituitrin,  and  in  still  greater  concentration  in  a  preparation 
to  which  the  name  hypophysin  has  been  given)  causes  a  great  rise 
of  blood-pressure,  due  partly  to  constriction  of  the  arterioles  and 
partly  to  an  increase  in  the  force  of  the  heart-beat,  both  of  which 
are  brought  about  by  direct  action.  This  rise  of  pressure  lasts  for 
a  considerable  time,  and  is  sometimes  accompanied  by  a  slowing 
of  the  heart.  A  second  dose  injected  before  the  effect  of  the  first 
has  passed  off  is  inactive;  and  this  distinguishes  the  pituitary  from 
the  suprarenal  extract.  Associated  with  the  pressor  effect  is  an 
increase  in  the  flow  of  the  urine.  Whether  this  is  due  to  a  separate 
diuretic  substance,  as  some  maintain,  has  not  been  definitely  settled. 
The  pressor  substance,  unlike  adrenalin,  directly  stimulates  smooth 
muscle  fibres  (especially  the  arteries,  uterus,  and  spleen)  irrespective 
of  their  innervation  (Dale).  Hypophysin  has  been  employed  to 
stimulate  the  uterine  contractions  in  obstetrical  practice  with 
apparently  satisfactory  results.  When  injected  intramuscularly, 
regular  and  powerful  contractions  of  the  uterus  are  excited  in  two 
or  three  minutes  at  any  stage  in  parturition.  The  depressor  sub- 
stance produces  a  marked  fall  of  blood-pressure,  even  when  it  is 
injected  during  the  rise  of  pressure  caused  by  an  injection  of  the 
pressor  substance.  The  anterior  lobe,  or  hypophysis,  also  contains 
a  depressor  substance.  Intravenous  injection  of  a  saline  extract 
causes  a  distinct  fall  of  blood-pressure,  accompanied  usually  by 
acceleration  and  weakening  of  the  heart  (Fig.  207).  A  second  in- 
jection immediately  following  the  first  produces  no  change  in  the 
pressure.  But  extracts  of  many  organs,  including  the  nervous 
tissues,  cause  a  similar  fall  of  pressure,  and  there  is  no  evidence 
that  the  depressor  substance  of  the  anterior  lobe  is  specific  to  the 
pituitary  (W.  W.  Hamburger). 


648  INTERNAL  SECRETION 

It  is  not  at  present  possible  to  deduce  from  such  clinical  and 
experimental  observations  as  those  described  any  coherent  theory 
of  the  function  of  the  pituitary.  That  there  is  some  connection 
between  the  normal  action  of  the  gland,  and  in  particular  of  its 
anterior  lobe,  and  the  normal  growth  and  nutrition  of  the  skeleton 
is  scarcely  to  be  doubted.  The  fact  that  administration  of  the 
dried  gland  substance  to  dogs  causes  an  increased  excretion  of  cal- 
cium on  a  diet  rich  in  calcium  is  a  further  indication  of  its  influence 
on  the  metabolism  of  bone  (Malcolm).  But  so  far  is  the  precise 
nature  of  this  influence,  if  it  exists,  from  being  fully  understood, 
that  authorities  of  repute  are  still  divided  on  the  question  whether 
the  symptoms  of  acromegaly  and  gigantism  are  due  to  atrophy  or 
to  hypertrophy  of  the  active  elements  of  the  gland,  to  loss  of  its 
internal  secretion,  or  to  its  manufacture  in  excessive  amount. 
There  is  evidence  that  the  colloid  secretion  of  the  posterior  lobe, 
probably  formed  by  the  epithelial  cells  of  the  pars  intermedia, 
passes  through  the  nervous  portion  to  enter  the  infundibulum  and 
the  third  ventricle  of  the  brain,  where  it  breaks  down  in  the  cerebro- 
spinal fluid  (Herring).  And  it  has  been  suggested  that  in  virtue 
of  the  action  of  the  hormones  (p.  398)  in  this  secretion  on  the  vas- 
cular system  in  general,  and  on  the  renal  cells  and  the  renal  circula- 
tion in  particular,  the  posterior  lobe  constitutes  a  mechanism  for 
the  control  of  the  secretion  of  urine.  But  this  suggestion  is  still  in 
the  realm  of  hypothesis. 

Pineal  Gland. — Extracts  of  the  pineal  gland  injected  into  the  circula- 
tion have  no  effect  other  than  that  due  to  the  inorganic  constituents 
of  the  calcareous  concretions  or  'brain  sand,'  which  are  its  character- 
istic feature.  Since  in  early  life  the  organ  has  a  glandular  structure 
which  is  later  replaced  by  fibrous  tissue,  it  has  been  supposed  that  it 
may  exercise  some  function  in  connection  with  growth.  But  so  far 
the  physiology  of  the  pineal  body  is  practically  a  blank  sheet.  The 
alleged  influence  of  the  invasion  of  the  gland  in  young  children  by 
pathological  growths  in  accelerating  the  development  of  the  skeleton 
and  reproductive  organs,  which  has  been  supposed  to  indicate  that  it 
normally  exerts  a  restraining  or  regulative  influence  on  this  develop- 
ment, is  at  present  purely  fanciful. 

Kidney. — The  experiments  of  Bradford,  which  seemed  to  indicate 
that  the  kidney,  in  addition  to  its  function  as  an  excretory  organ,  plays 
an  important,  and  indeed  indispensable,  part  in  protein  metabolism, 
possibly  by  forming  something  of  the  nature  of  an  internal  secretion, 
have  not  been  confirmed.  He  stated  that,  when  the  half  or  two-thirds 
of  one  kidney  and  the  whole  of  the  other  have  been  removed  from  a 
dog  by  successive  operations,  death  ensues,  although  the  quantity  both 
of  water  and  urea  excreted  by  the  fragment  of  renal  substance  that 
remains  is  far  above  the  normal.  In  spite  of  the  increased  elimination 
of  urea,  that  substance  was  said  to  accumulate  in  the  tissues,  showing 
that  the  destruction  of  protein  was  increased — a  conclusion  which 
seemed  to  derive  support  from  the  wasting  of  the  animal.  It  has  since 
been  shown  that  an  increased  output  of  nitrogen  is  not  of  constant 
occurrence,  and  only  takes  place  under  the  same  conditions  as  in 
starvation  (p.  593).     As  a  matter  of  fact,  the  animals  waste  and  die 


KIDNEY 


649 


within  a  few  days  or  weeks  largely  because  they  refuse  to  eat.  Polyuria 
(increase  of  urine  beyond  the  normal)  does  not  necessarily  occur.  It 
is  well  known  that  when  only  one  kidney  is  extirpated  the  other  hyper- 
trophies, and  no  ill-effects  ensue. 

The  statement  that  extracts  of  the  kidney  when  injected  into  the 
veiiis  of  an  animal  cause  a  rise  of  arterial  blood-pressure,  essentially 


Fig.  208. — Effect  of  Bone-Marrow  on  Blood- Pressure.  Intravenous  Injection  of 
Saline  Extract.  Vagi  Intact.  The  uppermost  line  is  a  signal  trace  showing  the 
time  and  length  of  injection.  Below  this  is  the  record  of  the  respiratory  move- 
ments, and  lowest  the  blood-pressure  tracing.     To  be  read  from  left  to  right. 

through  direct  action  on  the  peripheral  vaso-motor  mechanism,  is  of 
considerable  interest,  for  it  may  possibly  have  some  bearing  on  the  rise 
of  pressure  and  consequent  hypertrophy  of  the  heart  associated  with 
certain  renal  diseases.  But  there  is  not  as  yet  sufficient  evidence  that 
the  hypothetical  pressor  substance,  to  which  the  name  '  renin  '  has 
been  given,  in  any  sense  represents  an  internal  secretion  of  the  kidney. 

The   pressor  substance    (so-called    — m 1 . — 

'  urohypertensine  ')  which  can  be 
extracted  by  ether  from  normal 
human  urine  (Abelous)  is  probably 
only  excreted  by  the  kidney,  and 
perhaps  arises  from  the  putrefac- 
tion of  proteins  in  the  intestine. 
For  it  has  been  shown  that  in  the 
putrefaction  of  (horse-)  meat  bases 
are  formed  which,  when  injected 
intravenously,  cause  a  rise  of 
blood-pressure.  The  most  active 
of  these  is  a  body  known  as 
/j-hydroxyphenylethylamine, 
formed  from  tyrosin  (Barger  and 
Walpole).  Whether  the  pressor 
(vaso-constrictor)  substance  which  appears  to  be  liberated  from  the 
platelets  when  blood  is  shed,  and  may  therefore  be  presumed  to  be  more 
slowly  liberated  from  such  platelets  as  normally  break  down  in  the 
circulating  blood,  has  any  relation  to  the  pressor  substance  of  urine 
is  unknown.  It  is  also  quite  uncertain  whether,  as  has  been  stated  by 
some  observers,  extracts  of  the  kidney  or  blood  from  the  renal  vein 
stave  off  for  a  time  the  onset  of  the  uraemic  symptoms  that  follow 


Fig.  209. — Injection  of  Extract  of  Bone- 
Marrow  with  the  Vagi  Cut.  To  be  read 
from  left  to  right. 


650  INTERNAL  SECRETION 

removal  of  both  kidneys  or  tmeliorate  them  when  they  have  already 
appeared. 

The  spleen  does  not  produce  an  internal  secretion  necessary  to  life, 
for  it  can  be  removed  both  in  animals  and  in  man,  not  only  without 
causing  death,  but  often  without  the  development  of  any  serious 
symptoms.  Its  blood-forming  and  blood-destroying  functions  (p.  22) 
are  taken  on  by  other  structures  (particularly  the  red  bone-marrow), 
but  the  formation  of  the  bile-pigment  is  interfered  with,  and  its  amount 
reduced  by  more  than  50  per  cent.  (Pugliese).  The  production  of 
trj'^psinogen  by  the  pancreas  is  also  said  to  be  diminished,  whereas  if 
an  extract  of  spleen  be  injected  into  the  circulation  of  an  animal 
deprived  of  its  spleen,  the  amount  of  trypsinogen  is  increased.  It  has, 
therefore,  been  supposed  that  the  spleen  forms  a  substance  (protryp- 
sinogen)  which,  passing  into  the  blood,  is  taken  up  by  the  pancreas  and 
elaborated  into  tr^-psinogen  (p.  405). 

The  salivary  glands  may  be  extirpated  without  any  sensible  change 
being  produced  in  the  normal  metabolism.  There  is  evidence,  how- 
ever, that  the  secretion  of  the  gastric  juice  is  diminished.  It  has  been 
supposed  that  this  may  be  due  to  the  absence  of  a  hormone  (p.  398) 
normally  produced  in  the  salivary  glands.  A  temporary  increase  in 
the  gastric  secretion  is  caused  when  extracts  of  the  glands  of  normal 
dogs  are  injected  into  the  veins  or  into  the  peritoneal  cavity  of  dogs 
deprived  of  their  salivary  glands  (Hemmeter). 

Extracts  of  nervous  tissue  (sciatic  nerve,  white  matter  of  brain,  and 
spinal  cord,  but  especially  grey  matter  of  brain)  cause,  on  injection  into 
the  veins,  a  decided  fall  of  arterial  blood-pressure,  which  soon  passes 
off,  and  can  be  renewed  by  a  fresh  injection.  The  fall  of  pressure  is 
due  to  direct  action  upon  the  bloodvessels  of  a  depressor  substance  in 
the  extracts,  and  not  to  the  action  of  vaso-motor  nerves.  It  can  be 
obtained  after  section  of  the  vagi. 

Extracts  of  muscular  tissue  also  cause  a  distinct  though  transient 
fall  of  pressure,  but  not  so  great  a  fall  as  in  the  case  of  extracts  of 
nervous  tissue.  Saline  decoctions  of  other  tissues  (testis,  kidney, 
spleen,  pancreas,  liver,  mucous  membrane  of  stomach  and  intestine, 
lung,  and  mammary  gland)  all  produce  a  fall  of  blood-pressure  (Osborne 
and  Vincent).  The  same  is  true  of  bone-marrow  (Brown  and  Guthrie; 
Figs.  208,  209).  It  must  be  repeated  that  there  is  no  evidence  that 
these  depressor  substances  are  specific  internal  secretions  in  the  same 
sense  as  adrenalin. 


CHAPTER    XII 

ANIMAL  HEAT 

From  the  earliest  ages  it  must  have  been  noticed  that  the  bodies  of 
many  animals,  and  particularly  of  men,  are  warmer  than  the  air 
and  than  most  objects  around  them.  The  '  vulgar  opinion  '  of 
Bacon's  time,  '  that  fishes  are  the  least  warm  internally,  and  birds 
the  most,'  if  it  does  not  imply  a  very  extensive  knowledge  of  animal 
temperature,  at  least  shows  that  the  fundamental  distinction  of 
warm  and  cold-blooded  animals,  which  is  to-day  more  accurately 
expressed  as  the  distinction  between  animals  of  constant  tempera- 
ture (homoiothermal)  and  animals  of  variable  temperature  (poikilo- 
thermal),  had  been  grasped,  and  was  even  popularly  knowTi.  Since 
that  time  the  accumulation  of  accurate  numerical  results,  and  the 
advance  of  physical  and  physiological  doctrine,  have  given  us 
definite  ideas  as  to  the  relation  of  animal  heat  to  the  metabolic 
processes  of  the  body.  It  is  impossible  to  understand  the  present 
position  of  the  subject  \nthout  an  elementary'  knowledge  of  the 
science  of  heat.  For  this  the  student  is  referred  to  a  textbook  of 
physics.  All  that  can  be  done  here  is  to  preface  the  physiological 
portion  of  the  subject  by  a  few  remarks  on  the  physical  methods  and 
instruments  employed: 

Section  I. — Thermometry  axd  Calorimetry. 

Temperature. — Two  bodies  are  at  the  same  temperature  if,  when 
placed  in  contact,  no  exchange  of  heat  takes  place  between  them. 
They  are  at  different  temperatures  if,  on  the  whole,  heat  passes  from 
one  to  the  other,  and  that  body  from  which  the  heat  passes  is  at  the 
higher  temperature.  It  is  known  by  experiment  that  if  two  bodies  of 
different  temperature  are  placed  in  contact,  heat  will  pass  from  one  to 
the  other  till  they  come  to  have  the  same  temperature.  If,  then,  we 
have  the  means  of  finding  out  the  temperature  of  any  one  body,  we 
can  arrive  at  the  temperature  of  any  other  by  placing  the  two  in  con- 
tact for  a  sufficiently  long  time,  under  the  proviso  that  the  quantity  of 
heat  necessary  to  bring  the  temperature  of  the  first  body,  which  may  be 
called  the  '  measuring  '  body,  to  equality  with  that  of  the  second  is  so 
small  as  not  to  make  a  sensible  difference  in  the  latter.  This  is  the 
principle  on  which  thermometric  measurements  depend.  A  mercurial 
thermometer  consists  of  a  quantity  of  mercurj'  ordinarily  contained  in 
a  thin  glass  bulb,  the  cavity  of  which  is  continued  into  a  tube  of  very 

651 


652  ANIMAL  HEAT 

fine  bore  in  the  stem.  Like  most  other  substances,  mercury  expands 
when  the  temperature  rises,  and  contracts  when  it  sinks,  and  the  amoui.t 
of  expansion  or  contraction  is  shown  by  the  rise  or  fall  of  the  mercurial 
column  in  the  stem  of  the  thermometer.  The  point  at  which  the 
meniscus  stands  when  the  bulb  is  immersed  in  melting  ice  or  ice-cold 
water  is,  on  the  centigrade  scale,  taken  as  zero ;  the  point  at  which  it 
stands  when  the  thermometer  is  surrounded  by  the  steam  rising  from 
a  vessel  of  boiling  water  is  taken  as  loo  degrees.  The  intermediate 
portion  of  the  stem  is  divided  into  degrees  and  fractions  of  degrees. 
When,  now,  we  measure  the  temperature  of  any  part  of  an  animal  with 
such  a  thermometer,  we  place  the  bulb  in  contact  with  the  part  until 
the  mercury  has  ceased  to  rise  or  fall.  We  know  then  that  the  mercury 
has  ceased  to  expand  or  contract,  and  therefore  that  its  temperature 
is  stationary,  and  presumably  the  same  as  that  of  the  part.  It  is  to 
be  noted  that  we  have  gained  no  information  whatever  as  to  the  amount 
of  heat  in  the  body  of  the  animal.  We  have  only  observed  that  the 
mercury  of  the  thermometer  when  its  temperature  is  the  same  as  that 
of  the  given  part  expands  to  an  extent  marked  by  the  division  of  the 
scale  at  which  the  column  is  stationary.  And  we  know  that  if  the 
mercury  rises  to  the  same  point  when  the  thermometer  is  applied  to 
another  part,  the  temperature  of  the  latter  is  the  same  as  that  of  the 
first  part;  if  the  mercury  rises  higher,  the  temperature  is  greater;  if 
not  so  high,  it  is  less.  The  thermometer,  then,  only  informs  us  whether 
heat  would  flow  from  or  into  the  part  with  which  it  is  in  contact  if 
the  part  were  placed  in  thermal  connection  with  any  other  body  of 
which  the  temperature  is  known.  In  other  words,  the  temperature  is 
a  measure  of  the  heat  '  tension,'  so  to  speak ;  and  difference  of  tempera- 
ture between  two  bodies  is  analogous  to  difference  of  potential  between 
the  poles  of  a  voltaic  cell  (p.  698),  or  to  difference  of  level  between  the 
surface  of  a  mill-pond  and  the  race  below  the  wheel. 

The  temperature  of  an  animal  is  measured  in  one  of  the  natural 
cavities,  as  the  rectum,  vagina,  mouth,  or  external  ear,  or  in  the  axilla, 
or  at  any  part  of  the  skin.  For  the  cavities  a  mercury  thermometer 
is  nearly  always  used ;  the  ordinary  little  tnaxinium  thermometer  is  most 
convenient  for  clinical  purposes.  The  temperature  of  the  skin  may  be 
measured  by  an  ordinary  mercury  thermometer,  the  outer  portion  of 
the  bulb  of  which  is  covered  by  some  badly  conducting  material.  An 
uncovered  thermometer,  heated  nearly  to  the  temperature  expected, 
will  also  give  results  sufficiently  accurate  for  most  purposes,  especially 
if  the  bulb  is  flat  or  in  the  form  of  a  flat  spiral,  which  can  be  easily 
applied  to  the  surface.  A  theoretically  better  method,  but  more 
laborious  in  practice,  is  the  use  of  a  thermo-electric  junction,  or  a  resist- 
ance thermometer  formed  of  a  grating  cut  out  of  thin  lead-paper  or  tin- 
foil (Fig.  210).  This  is  especially  useful  for  comparing  the  temperature 
of  two  portions  of  skin .  The  temperature  of  the  solid  tissues  and  liquids 
of  the  body  may  also  be  measured  or  compared  by  the  insertion  of  mer- 
curial or  resistance  thermometers  or  thermo-electric  junctions  (p.  737). 

Calorimetry. — The  quantity  of  heat  given  off  by  an  animal  is  generally 
measured  by  the  rise  of  temperature  which  it  produces  in  a  known 
mass  of  some  standard  substance.  Sometimes,  however,  as  in  the  ice- 
calorimeter  of  Lavoisier  and  Laplace,  and  the  ether  calorimeter  of 
Rosenthal,  a  physical  change  of  state — in  the  one  case  liquefaction  of 
ice,  in  the  other  evaporation  of  ether — is  taken  as  token  and  measure 
of  heat  received  by  the  measuring  substance,  the  number  of  units  of 
heat  corresponding  to  liquefaction  of  unit  mass  of  ice  or  evaporation  of 
unit  mass  of  ether  being  known.  The  unit  generally  adopted  in  the 
measurement  of  heat  is  the  quantity  required  to  raise  the  temperature 


THERMOMETRY  AND  CALORIMETRY 


653 


r 


\w 


of  a  kilogramme  of  water  1°  C,  which  is  called  a  caloric,*  or  kilocalorie 
or  large  calorie.  The  thousandth  part  of  this,  the  quantity  needed  to 
raise  the  temperature  of  a  gramme  of  water  by  1°,  is  termed  a  small 
calorie  or  millicalorie  or  gramme -caloric. 

In  the  calorimeters  which  ha\'e  been  chiefly  used  in  physiology  either 
water  or  air  has  been  taken  as  the  measuring  sul)stance.  The  simplest 
form  of  water  calorimeter  is  a  box  with  double  walls,  the  space  between 
whi'h  is  filled  with  a  weighed  quantity  of  water.  The  animal  is  placed 
inside  the  \csscl,  and  the  temperature  of  the  water  noted  at  the  begin- 
ning and  end  of  the  experiment.  Su{'j)ose  that  the  quantity  of  water 
is  10  kilos,  and  that  the  temperature  rises  i^  in  thirty  minutes,  then  the 
amount  of  heat  lost  by  the  animal  is 
10  calories  in  the  half-hour,  or  480 
calories  in  the  twenty-four  hours;  and 
if  the  rectal  temperature  is  unchanged, 
this  will  also  be  the  amount  of  heat 
produced. 

Here  we  assume  (i)  that  all  the  heat 
lost  by  the  animal  has  gone  to  heat  the 
water  and  none  to  heat  the  metal  of  the 
calorimeter;  (2)  that  none  has  been 
radiated  away  from  the  outer  surface  of 
tho  latter.  The  first  assumption  will 
seldom  introduce  any  sensible  error  in  a 
prolonged  physiological  experiment ;  but 
it  is  very  easy  to  determine  by  a  separate 
observation  the  water-equivalent  of  the 
calorimeter — ^that  is,  the  quantity  of 
water  whose  temperature  will  be  raised  1° 
by  a  quantity  of  heat  which  j  ust  suffices 
to  raise  the  temperature  of  the  metal  by 
1°  (p.  694).  Then  the  water-equivalent 
is  added  to  the  quantity  of  water  actu- 
ally present,  and  the  sum  is  multiplied  by 
the  rise  of  temperature.  If  the  tempera- 
ture of  the  room  is  constant,  as  will  be 
approximately  the  case  in  a  cellar,  any 
error  due  to  interchange  of  heat  between 
the  calorimeter  and  its  surroundings  may  be  eliminated  by  making  the 
initial  temperature  of  the  water  as  much  less  than  that  of  the  air  as  the 
final  temperature  exceeds  it.  Then  if  the  loss  of  heat  by  the  animal  is 
uniform,  as  much  heat  is  gained  during  the  first  half  of  the  experiment 
by  the  calorimeter  from  the  air  as  is  lost  by  it  to  the  air  during  the  last 
half.  Or,  without  lowering  the  temperature  of  the  water,  the  amount 
of  heat  lost  by  the  calorimeter  during  an  experiment  may  be  previously 
determined  by  a  special  observation,  and  added  to  the  quantity  cal- 
culated from  the  observed  rise  of  temperature.  Or,  finally,  two  similar 
calorimeters  may  be  used,  one  containing  the  animal  and  the  other  a 
hydrogen  flame,  or  a  coil  of  wire  traversed  by  a  voltaic  current,  which 
is  regulated  so  as  to  keep  the  temperature  the  same  in  the  two  calorim- 
eters. From  the  quantity  of  hydrogen  burnt,  or  electricity  passed, 
the  heat-production  of  the  animal  can  be  calculated. 

In  Atwater's  great  respiration  calorimeter  (Fig.  211)  both  the  heat 
production  and  the  respiratory  exchange  are  measured.  The  heat  pro- 
duced by  the  person  in  the  calorimeter  is  carried  away  from  it  by  a 

♦  The  sttidi-nt  should  carefully  note  that  when  the  term  'calorie'  is  used 
without  qualification,  a  large  calorie,  i.e.,  i, 000  gramme  calories,  is  meant. 


Fig.  210. — Resistance  Thermom- 
eter for  measuring  Temperature 
of  Skin.  G,  grating  of  lead- 
paper,  attached  to  a  cover-slip, 
and  mounted  on  a  holder;  W, 
W,  wires  to  the  Wheatstone's 
bridge.  An  increase  of  tem- 
perature causes  an  increase  in 
the  resistance  of  the  lead.  The 
balance  of  the  bridge  is  thus  dis- 
turbed. By  experimental  grad- 
uation the  temperature  value 
of  the  deflection,  or  of  the  change 
of  resistance  that  balances  it,  is 
known  (p.  699). 


654 


ANIMAL  HEAT 


stream  of  water  flowing  through  the  chamber  in  a  series  of  tubes,  the 
temperature  within  the  calorimeter  being  kept  constant  by  regulating 
the  temperature  and  velocity  of  the  entering  stream  of  water.  The 
quantity  of  the  escaping  water  and  the  increase  in  its  temperature  are 
measured,  and  the  heat  production  can  then  be  calculated.  The 
apparatus  consists  of  a  chamber  in  which  a  human-  being  can  live  for 
several  days  and  nights.  A  stream  of  air  is  supplied,  and  the  chemical 
changes  produced  in  this  are  investigated  in  the  manner  already 
described  (p.  239). 


Fig.  211. — Respiration  Calorimeter  (Atwater).  Interior  of  chamber.  A  corner  of 
the  inner  copper  wall  is  supposed  to  be  taken  away.  The  ventilating  air-current 
enters  the  chamber  at  the  lower  end  of  W,  and  leaves  the  chamber  through  the 
long  tube  fastened  above  W.  The  copper  tubes  H,  H  are  surrounded  by  copper 
discs  I,  I,  fastened  on  them  like  a  string  of  beads  to  increase  the  surface.  These 
tubes  constitute  the  arrangement  through  which  the  stream  of  water  flows  which 
removes  the  heat  formed  in  the  chamber.  J,  J  are  copper  troughs  which  receive 
the  water  dropping  from  H,  H.  M,  M,  M  are  electrical  thermometers  which  show 
the  temperature  of  the  chamber;  N,  N,  similar  thermometers  which  show  the 
temperature  of  the  copper  wall. 

Air  calorimeters  have  sometimes  been  used  for  physiological  pur- 
poses. A  diagram  of  one  is  shown  in  Fig.  212.  Such  calorimeters  are 
really  thermometers  with  an  immense  radiating  surface,  for  only  a 
small  proportion  of  the  heat  given  off  by  the  animal  goes  to  heat  the 
measuring  substance.  The  heat  required  to  raise  the  temperature  of  a 
litre  of  air  by  1°  is  very  small  in  comparison  with  that  required  to  raise 
the  temperature  of  a  litre  of  water  by  the  same  amount.     Hence  a  given 


THERMOMETRY  AND  CALORIMETRY 


655 


quantity  of  heat  raises  the  temperature  of  an  air  calorimeter  much  more 
than  that  of  a  water  calorimeter  of  the  same  dimensions ;  and  the  loss 
of  heat  to  the  surroundings  being  proportional  to  the  elevation  of  tem- 
perature, in  the  water  calorimeter  the  chief  part  of  the  heat  is  actually 
retained  in  the  water,  while  in  an  air  calorimeter  the  greater  portion 
passes  through  the  air  space,  and  is  radiated  away.  When  the  amount 
of  heat  lost  by  the  calorimeter  becomes  equal  to  that  gained  from  the 
animal,  the  '  steady  '  reading  of  the  instrument  is  taken,  and  from  this 
the  heat  production  can  be  deduced  by  an  experimental  graduation  of 
the  apparatus.  One  advantage  of  an  air  calorimeter  is  that  it  follows 
more  closely  rapid  variations  in  the  heat  production  of  the  animator, 
to  speak  more  correctly,  in  the  heat  loss.     It  should  be  carefully  noted 


Fig.  212. — Air  Calorimeter.  (/.)  cross-section  (//.)■  longi- 
tudinal section;  A,  cavity  of  calorimeter  for  animal;  B,  copper 
cylinder  corrugated  so  as  to  increase  the  radiating  surface;  C,  air 
space  enclosed  between  B  and  a  concentric  copper  cylinder  F; 
C  is  air-tight,  and  is  connected  by  the  tube  2  with  the  manometer  M.  The 
.other  end  of  the  manometer  is  connected  with  an  exactly  similar  calorimeter,  in 
which  a  hydrogen  flame  is  burnt  in  the  space  corresponding  to  A,  or  in  which  the  air 
in  A  is  heated  by  a  coil  of  wire  traversed  by  an  electrical  current.  The  flame  or 
current  is  regulated  so  as  to  keep  the  coloured  petroleum  or  mercury  in  the  manometer 
M  at  the  same  level  in  both  limbs;  the  amount  of  heat  given  off  to  the  one  calorimeter 
by  the  flame  or  current  is  then  equal  to  that  given  off  by  the  animal  to  the  other. 
D  is  an  external  cylinder  of  copper  or  tin  perforated  by  holes  (6,  7)  at  intervals.  The 
purpose  of  it  is  to  prevent  draughts  from  affecting  the  loss  of  heat  from  F;  4,  5,  are 
tubes  through  which  thermometers  can  be  introduced  into  C;  i  is  the  terminal  of  a 
spiral  tube,  which  is  coiled  in  the  end  portion  of  the  air  space  C.  The  sections  of  the 
coils  are  indicated  by  small  circles.  The  other  end  of  the  spiral  tube  is  3 ;  through 
this  tube  air  is  sucked  out,  and  so  the  proper  ventilation  of  the  animal  is  kept  up. 
The  object  of  the  spiral  arrangement  is  that  the  air  aspirated  out  of  A  may  give  up 
its  heat  to  the  air  in  C  before  passing  out.     E  is  a  door  with  double  glass  walls. 

that  in  calorimetry  what  is  directly  measured  is  the  quantity  of  heat 
given  out  by  the  animal,  not  the  quantity  produced.  The  two  quanti- 
ties are  identical  only  when  the  temperature  of  the  animal  has  remained 
unchanged  throughout  the  experiment.  If  the  temperature  has  fallen, 
the  quantity  of  heat  produced  is  equal  to  the  quantity  measured  by  the 
calorimeter  minus  the  difference  between  the  quantity  in  the  animal  at 
the  beginning  and  at  the  end  of  the  observation.  This  difference  is 
equal  to  the  average  specific  heat  of  the  animal  multiplied  by  its  weight 
and  by  the  fall  of  temperature.  It  can  be  approximately  found  by 
multiplying  the  weight  (in  kilogrammes  or  grammes)  by  the  fall  of 
rectal  temperature  (in  degrees),  since  the  average  specific  heat  of  the 
body  is  not  very  difft-rent  from  that  of  water,  and  the  specific  heAt  of 
water  is  taken  as  unity. 


656  ANIMAL  HEAT 

The  differential  micro-calorimeter  of  A.  V.  Hill  is  the  most  accurate 
apparatus  for  measuring  very  small  quantities  of  heat — e.g.,  the  heat 
given  off  by  resting  muscles,  or  by  muscles  during  the  process  of  heat 
rigor,  or  in  such  reaetions  as  the  souring  of  milk  by  the  lactic  acid 
bacillus.  It  consists  of  a  pair  of  Dewar  flasks  (ordinary  thermos  oi 
vacuum  bottles),  in  which  loss  of  heat  to  the  surrpundings  is  greatly 
hindered  by  exhausting  the  air  from  the  space  enclosed  by  the  double 
wall  of  the  flask.  The  bottles  are  packed  in  sawdust  in  cylindrical  tins. 
The  tissue  or  liquid  experimented  with  is  put  into  one  flask,  and  water 
into  the  other  (control)  flask,  and  the  amount  of  the  water  is  adjusted 
so  that  the  change  of  temperature  of  each  flask  due  to  conduction  and 
radiation  to  or  from  the  outside  is  the  same.  Loss  of  heat  is  thus 
automalically  eliminated,  and  from  the  excess  of  temperature  of  the 
experimental  over  that  of  the  control  flask  the  heat  production  in  the 
former  can  be  calculated.  The  temperatures  are  measured  by  thermo- 
electric junctions  of  an  alloy  called  constantan  and  copper,  one  junction 
being  in  each  flask.  To  economize  time  in  making  such  observations, 
a  number  of  pairs  of  flasks  can  be  simultaneously  employed.  The 
apparatus  is  so  sensitive  that  a  liberation  in  ten  hours  of  i  gramme- 
calorie  per  gramme  of  contents  of  the  flask  can  be  followed  and  esti- 
mated with  an  error  not  exceeding  3  per  cent. 

Body -Temperature. — All  the  higher  animals  (mammals  and  birds) 
have  a  practically  constant  internal  temperature  (fowl  41°  to  44°  C, 
mouse  37°  to  38°,  dog  38°  to  39°,  man  37°  in  the  rectum),  but  a  few 
hibernating  mammals,  such  as  the  marmot,  are  homoiothermal  in 
summer,  poikilothermal  during  their  winter  sleep.  In  the  lower 
foims  the  body-temperature  follows  closely  the  temperature  of  the 
environment,  and  is  never  very  much  above  it  (frog  0-5°  to  2°  above 
external  temperature).  Both  in  a  frog  and  in  a  pigeon  heat  is 
evolved  as  long  as  life  lasts;  but  per  unit  of  weight  the  amphibian 
produces  far  less  than  the  bird,  and  loses  far  more  readily  what  it 
does  produce.  The  temperature  of  the  frog  may  be  25°  C.  in  June 
and  5°  in  January.  The  structure  of  its  tissues  is  unaltered,  and 
their  vitality  unimpaired  by  such  violent  fluctuations.  But  it  is 
necessary,  not  only  for  health,  but  even  for  life,  that  the  internal 
temperature  (the  temperature  of  the  blood)  of  a  man  should  vary 
only  within  relatively  narrow  limits  around  the  mean  of  37°  to 

38°  c. 

Why  it  is  that  a  comparatively  high  temperature  should  be 
needed  for  the  full  physiological  activity  of  the  tissues  of  a  mammal, 
while  the,  in  many  respects,  similar  tissues  of  a  fish  work  perfectly, 
although  perhaps  more  sluggishly,  at  a  much  lower  temperature,  is 
not  quite  clear.  Nor  do  we  know  the  precise  significance  of  that 
relative  constancy  of  temperature  in  the  warm-blooded  animal, 
which  is  as  important  and  peculiar  as  its  absolute  height.  The 
higher  animals  must  possess  a  superior  delicacy  of  organization, 
hardly  revealed  by  structure,  which  makes  it  necessary  that  they 
should  be  shielded  from  the  shocks  and  jars  of  varying  temperature 
that  less  highly  endowed  organisms  endure  with  impunity.  Leaving 
the  discussion  of  the  local  differences  and  periodic  variations  of  the 


INCOME  AND  EXPENDITURE  OF  THE  BODY  657 

temperature  of  warm-blooded  animals  to  a  future  page,  let  us 
consider  now  the  mechanism  by  which  the  loss  of  heat  is  adjusted 
to  its  production,  so  that  upon  the  whole  the  one  balances  the  other. 

Section  II. — Income  and  Expenditure  of  the  Body  in  Terms 

OF  Energy. 

Heat-Loss. — Heat  is  lost  (i)  from  the  surfaces  of  the  body  by 
radiation,  conduction,  and  convection;  (2)  as  latent  heat  in  the 
watery  vapour  given  off  by  the  skin  and  lungs;  and  (3)  in  the 
excreta.  Even  in  the  bulky  excrement  of  herbivora  a  compara- 
tively trifling  part  of  the  total  heat  is  lost.  The  second  channel 
of  elimination  is  much  more  important;  the  first  is  in  general  the 
most  important  of  all. 

The  loss  of  heat  by  direct  radiation  from  a  portion  of  the  skin  or 
clothes,  or  from  hair,  fur,  or  feathers  covering  the  skin,  may  be  measured 
by  means  of  a  thermopile  or  a  resistance  radiometer  (bolometer).  The 
latter  instrument  is  similar  in  principle  and  allied  in  construction  to  the 
resistance  thermometer  used  in  measuring  superficial  temperatures, 
and  already  described  (Fig.  210,  p.  653).  It  may  consist  of  a  grating 
of  lead-paper  or  tinfoil  fixed  vertically  in  a  small  box  which  protects 
it  from  draughts.  The  box  has  a  sliding  lid,  which  is  kept  closed  till 
the  moment  of  the  observation,  when  it  is  withdrawn  and  the  portion 
of  skin  applied  to  the  opening  at  a  fixed  distance  (5  to  10  cm.)  from  the 
grating.  The  intensity  of  radiation  depends  on  the  excess  of  tempera- 
ture of  the  radiating  surface  over  that  of  the  surroundings,  as  well  as 
on  the  nature  of  the  surface.  The  uncovered  parts  of  the  skin  (face 
and  hands  in  man)  radiate  more  per  unit  of  area  than  the  clothes  or 
hair;  and  the  warm  forehead  more  than  the  comparatively  cool  lobe 
of  the  ear  or  tip  of  the  nose.  When  a  man  is  sitting  at  rest  in  a  still 
atmosphere,  pure  radiation  plays  a  greater,  and  conduction  and  con- 
vection play  a  smaller,  part  in  the  total  loss  of  heat  from  the  skin  than 
when  he  is  walking  about  or  sitting  in  a  draught.  The  more  rapidly 
the  air  in  contact  with  the  skin  and  clothes  is  renewed,  the  lower,  other 
things  being  equal,  the  temperature  of  the  radiating  surfaces  is  kept, 
the  greater  is  the  loss  of  heat  by  conduction  to  the  adjacent  portions  of 
air,  and  the  smaller  the  loss  by  radiation  to  the  walls  of  the  room,  the 
furniture,  and  other  surrounding  objects.  It  is  probable  that,  under 
the  most  favourable  conditions,  the  amount  of  heat  lost  from  the  sur- 
face by  true  radiation  does  not  exceed  the  amount  lost  by  conduction 
and  convection. 

The  loss  of  heat  by  evaporation  of  water  from  the  skin  can  be  calcu- 
lated if  we  know  tlie  quantity  of  water  so  given  off.  For  a  granime  of 
water  at  the  ordinary  temperature  (say  15°  C.)  needs  0-555  calorie  to 
convert  it  into  aqueous  vapour  at  the  average  temperature  of  the  skin. 
If  we  take  the  average  quantity  of  water  excreted  as  sweat  in  twenty- 
four  hours  as  750  c.c,  this  will  be  equivalent  to  a  heat-loss  of  4i6'25 — 
say,  in  round  numbers,  400  largo  calories. 

The  quantity  of  heat  given  off  by  the  lungs  may  be  also  deduced 
from  calculation,  the  data  being  (i)  the  weight,  temperature,  and 
specific  heat  of  the  expired  air,  and  (2)  the  excess  of  water  it  contains 
in  the  form  of  aqueous  vajwur  over  that  contained  in  the  inspired  air. 
Helmholtz  calculated  tlie  quantity  of  heat  needed  to  warm  the  air 

42 


658 


ANIMAL  HEAT 


expired  by  a  man  in  twenty-four  hours  from  an  initial  temperature  of 
20°  to  body-temperature,  at  70  calories,  and  that  required  to  evaporate 
the  water  given  off  by  the  lungs  at  397,  making  the  total  heat-loss  by 
the  lungs  in  these  processes  from  400  to  500  calories.  A  certain  amount 
of  heat  is  also  absorbed  in  connection  with  the  escape  of  the  carbon 
dioxide.  The  reason  why  a  great  deal  more  water  and  therefore  more 
heat  is  not  given  off  by  the  lungs  with  their  enormous  surface,  and  the 
high  degree  of  imbibition  (p.  420)  of  the  epithelium  of  the  alveoli,  is 

Fig.  213. — ^  Calorimeter  for 
Measuring  Heat  given  off  in 
Respiration.  B,  copper  tube 
with  mouthpiece,  connected  with 
the  thin  brass  capsule  4;  4  is 
connected  with  a  similar  capsule 
3  by  a  short  tube,  which  passes 
out  from  it  at  the  side  opposite 
to  that  at  which  B  enters;  2  and 
I  are  similar  capsules.  From  i 
an  outlet  tube  C  passes  oS. 
The  whole  is  set  in  a  copper 
cylinder  A  filled  with  water. 
A  piece  is  supposed  to  be  cut  out 
of  A  in  order  to  show  the  cap- 
sules. A  is  placed  in  another 
wider  copper  cylinder. 

that  the  air  is  already  saturated  with  aqueous  vapour,  or  nearly  so, 
before  it  rca,ches  the  alveoli.  By  direct  calorimetric  observations  it 
was  found  that  a  man  of  70  kilos  weight  gave  off  in  normal  breathing, 
with  an  air-temperature  of  12°  to  15°  C,  from  350  to  450  calories. 
Forced  respiration,  as  might  be  expected,  increased  the  amount  often 
to  double  or  even  treble.  A  diagram  of  a  calorimeter  for  measuring 
the  heat  given  off  in  respiration  is  shown  in  Fig.  213.  (See  Practical 
Exercises,  p.  694.) 

The  following  table  gives  an  analysis  of  the  heat-loss  of  an  average 
man.  It  must  be  understood  that  the  figures  are  only  approximate. 
In  round  numbers  we  may  say  that  two-thirds  of  the  heat-loss  is 
due  to  radiation,  conduction,  and  convection,  and  one-third  to  the 
evaporation  of  water. 

(Evaporation  of  water 
Radiation*     -         -         -         - 
Conduction  (and  convection) 
J  Evaporation  of  water     - 
Lungs|j^^g^^-j^g  the  expired  air  - 

Heating  the  excreta 

100     2,590 

In  the  rabbit,  according  to  Nebelthau,  the  heat  lost  by  evaporation 
of  water  is  about  16  per  cent,  of  the  whole,  or  about  half  the  proportion 
in  man,  according  to  the  above  calculation.  This  is  not  surprising 
when  we  reflect  that  the  rabbit  does  not  sweat,  and  drinks  comparatively 
little  water. 

*  The  relative  amounts  lost  by  radiation  and  conduction  cannot  be  accur- 
ately fixed.     The  proportion  is  extremely  variable. 


Per  Cent. 

Calories. 

'5    1 

400 

25     [     80 

650 

40    J 

1,000 

2-5i      '7  5 

'400 
I    70 

2-5 

70 

INCOME  AND  FXPENDITURE  OF  ENERGY  659 

Sources  of  the  Heat  of  the  Body — Heat  Production. — Some  heat 
enters  the  body  as  such  from  without — in  the  food,  and  by  radiation 
from  the  sun  and  from  fires.  The  ultimate  source  of  all  the  heat 
produced  in  the  body  is  the  chemical  energy  of  the  food  substances. 
For  this  reason,  the  distinction  between  much  of  the  subject  matter 
of  this  chapter  and  that  of  Chapter  X.  is  scarcely  even  a  formal 
one.  Whatever  intermediate  forms  this  energy  may  assume — 
whether  the  mechanical  energy  of  muscular  contraction;  the  energy 
of  electrical  separation  by  which  the  currents  of  the  tissues  are 
produced;  the  energy  of  the  nerve  impulse;  or  the  energy,  be  it 
what  it  may,  which  enables  the  living  cells  to  perform  their  chemical 
labours — it  all  ultimately,  except  so  far  as  external  mechanical 
work  may  be  done,  appears  in  the  form  of  heat.  As  already  pointed 
out  (p.  536),  the  fraction  of  the  total  energy  hberated  in  the  pro- 
cesses of  hydrolytic  cleavage  is  comparatively  small.  Most  of  the 
heat  is  set  free  in  the  oxidative  processes  which  accompany  or  follow 
the  hydrolytic  changes. 

Thus  the  energy-value  of  a  gramme-molecule  (p.  420)  of  maltose, 
cane-sugar,  or  lactose  is  a  little  more  than  1,350  calories;  that  of  the 
two  gramme-molecules  of  dextrose  formed  by  hydrolysis  of  the  maltose 
is  1347*4  calories;  that  of  the  gramme-molecule  each  of  dextrose  and 
levulose  formed  from  the  cane-sugar,  1349-6;  and  that  of  the  gramme- 
molecule  each  of  dextrose  and  galactose  formed  from  the  lactose, 
1343-6  calories.  That  is  to  say,  the  hydrolysis  of  these  disaccharides 
to  monosaccharides,  which  is  the  first  step  in  their  metabolism,  is  accom- 
plished with  the  liberation  of  very  little  heat.  The  same  is  true  of  the 
splitting  of  the  fats  and  proteins.  The  dried  residue  of  a  filtered  pan- 
creatic digest  was  found  to  yield,  when  burned  in  the  calorimetric 
bomb,  only  10  per  cent,  less  heat  than  the  same  weight  of  dry  meat. 
Much  the  greater  part  of  this  deficiency  was  accounted  for  by  tke  leucin 
and  tyrosiu  which  had  crystallized  out,  and  the  derivatives  of  higher 
fatty  acids  in  the  meat,  as  these  would  be  removed  from  the  digest 
by  filtration. 

It  has  been  shown  that  the  law  of  the  conservation  of  energy  holds 
for  the  animal  body;  in  other  words,  there  is  a  practically  exact 
agreement  between  the  potential  energy  of  the  food  and  the  kinetic 
energy  into  which  it  is  transformed  in  the  body  both  during  rest 
and  during  work.  This  kinetic  energy  is  represented  by  the  heat 
given  off  plus  the  heat-equivalent  of  any  mechanical  work  done 
(Atwater).  In  other  words,  the  food,  whether  it  is  burned  in  a 
calorimeter  to  simple  end-products  like  carbon  dioxide  and  water, 
or  more  slowly  oxidized  in  the  body,  yields  the  same  amount  of 
heat,  provided  always  that  in  both  cases  it  is  entirely  consumed,  and 
that  no  work  is  transferred  to  the  outside.  In  the  body  the  com- 
bustion of  carbo-hydrates  and  fats  is  complete;  but  the  nitrogenous 
residues  of  the  proteins — urea,  uric  acid,  etc. — can  be  further 
oxidized,  and  the  remnant  of  energy  which  they  yield  must  be 
taken  into  account  in  any  calculation  of  the  total  heat-production 


66o  ANIMAL  HEAT 

founded  on  the  heat  of  combustion  of  the  food  substances.  From 
careful  experiments,  it  has  been  found  that  a  gramme  of  dry  protein 
(egg- albumin),  when  burned  in  a  calorimeter,  yields  5735  calories 
of  heat,  a  gramme  of  dextrose  3742,  and  a  gramme  of  animal  fat 
9-500  calories  (Stohmann). 

Calories. 

Heat-equivalent  of  i  gramme  of  albumin  -  5735 

Albumin  (minus  urea  produced  from  it)     -  »  4*949 

Cane-sugar  -  -  -  -  -  3-955 

Kreatin  (water-free)  .  _  _  _  4*275 

Starch  _._---  4-182 

In  applying  such  results  to  the  calculation  of  the  heat-production  of 
the  body,  it  is  not  sufficient  to  deduct  from  the  heat  of  combustion  of 
the  proteins  the  heat  which  the  residual  urea  would  yield  if  fully 
oxidized.  For  other  incompletely  oxidized  products  arise  from  pro- 
teins when  consumed  in  the  body,  and  Rubner  has  shown,  by  actually 
determining  the  heat  of  combustion  of  the  urine  arid  faeces,  that  the 
real  equivalent  of  a  gramme  of  albumin  is  at  most  only  4-420  calories. 
The  heat-equivalent  of  our  less  liberal  specimen  diet  (p.  613)  will  be 
approximately : 

Calories. 

Protein,  95  grammes  x        4*420  =  419*9 

Fat,  80  grammes  x        9*500  =  760-0 

Carbo-hydrate     (reckoned    as 

dextrose),  320  grammes  x        3-742  =         1,197-4 

2,3773 

The  heat-equivalent  of  the  more  generous  specimen  diet  (p.  614)  would 
be  2,878  calories. 

But  this  is  the  diet  of  a  man  doing  a  fair  day's  work,  and  to  get  the 
quantity  of  energy  which  actually  appears  as  heat,  the  heat-equivalent 
of  the  mechanical  work  performed  must  be  deducted.  A  fair  day's 
work  is  about  150,000  kilogramme-metres — that  is,  an  amount, equal 
to  the  raising  of  150,000  kilogrammes  to  the  height  of  a  metre.  Now, 
a  kilogramme-degree  or  calorie  of  heat  is  equivalent  to  425-5  kilo- 
gramme-metres of  work,   and  a   kilogramme-metre  to calorie. 

4-^5'5 

The  heat-equivalent  of  the  day's  work  is,  therefore,  150,000  x — — -  = 

352  calories.  Deducting  this  from  the  heat-equivalent  of  the  food, 
we  get  in  round  numbers  2,520  large  calories  as  the  heat  given  off  on 
the  more  liberal  diet.  This  corresponds  fairly  well  with  the  calculated 
heat-loss  (p.  658). 

The  table  on  p.  661,  based  on  the  direct  calorimetric  observations 
of  Atwater  and  Benedict,  shows  the  average  heat-production  in  a  large 
number  of  experiments  on  several  individuals  at  rest  and  doing  measured 
amounts  of  work,  with  a  stationary  bicycle,  for  instance.  This  was 
connected  with  a  small  dynamo,  which  transformed  the  greater  part 
of  the  work  into  electrical  energy.  The  electrical  energy  in  its  turn 
was  changed  into  heat,  the  current  passing  through  a  lamp. 

The  heat-production  during  the  hours  of  sleep,  in  the  second  night 
period,  is  much  less  than  in  the  waking  hours  of  rest,  and  of  course 
enormously  less  than  in  the  hours  of  work.  After  work  the  heat  pro- 
duction in  the  period  of  sleep  is  only  a  little  greater  than  after  rest. 

As  already  indicated  (p.  659),  it  is  permissible  to  calculate  the  heat- 


INCOME  AND  EXPENDITURE  OF  ENERGY 


66i 


production  from  the  diet,  and  Rubner  has  done  this  for  various  classes 
of  men,  reducing  everything  to  the  standard  of  a  body-weight  of 
67  kilos.  The  fasting  man,  of  67  kilos  body-weight,  produces  2,303  calo- 
ries in  the  twenty-four  hours.  The  class  of  brain- workers,  represented 
by  physicians  and  officials,  produce  only  a  little  more  heat  than  the 
fasting  man,  viz.,  2,445  calories.  The  second  class,  represented  by 
soldiers  (presumably  in  time  of  peace)  and  day-labourers  (probably  of 
a  cautious  and  conservative  type),  work  up  to  2,868  calories.  The 
third  class,  composed  of  men  who  work  with  machines  and  other  skilled 
labourers,  attain  a  heat-production  of  3,362  calories.  The  fourth  class, 
typified  by  miners  (who  are  engaged,  usually  by  the  piece  and  not  by 
the  day,  in  severe  and  exhausting  toil),  produce  as  much  as  4,790  calo- 
ries. In  the  fifth  and  last  class,  represented  by  lumberers  and  other 
out-of-door  labourers  (who,  in  addition  to  excessive  exertion,  have 
often  to  face  intense  cold),  the  heat-production  rises  to  5,360  calories. 
The  diet  of  ordinary  prisoners  in  Scotland,  doing  light  work,  chiefly  of 
a  sedentary  character,  was  found  to  correspond  to  3,115,  and  that  of 
convicts  on  '  hard  labour  '  to  3,707  calories.  It  is  a  fair  presumption 
that  in  Scotch  prisons  the  total  heat  value  supplied  is  not  excessive. 
From  the  general  agreement  of  calculated  results  with  actual  measure- 
ments we  can  safely  conclude  that  most  healthy  adults  produce  between 
2,000  and  3,000  large  calories  (35  to  40  per  kilo  of  body-weight)  on  a  '  rest ' 
day,  or  a  day  of  light  labour,  and  between  3,000  and  4,000  (45  to  60  per 
kilo  of  body-weight)  on  a  day  of  hard  manual  work. 


•-I 

So 
a.s 

Heat  eliminated  per  Hour. 

Percentage  of  Total  Heat 
in  24  Hours. 

Day-time. 

Night-time. 

Average 

per  Hour 

for  24 

Hours. 

Day-time. 

Night-time. 

7  a.m. 

to 
I  p.m. 

I  p.m. 

to 
7  p.m. 

7  p.m. 

to 
I  a.m. 

I  a.m. 

to 
7  a.m. 

7  a.m. 

to 
I  p.m. 

I  p.m. 

to 
7  p.m. 

7  p.m. 

to 
I  a.m. 

I  a.m. 

to 
7  a.m. 

Rest  experi- 
ments - 

Work  experi- 
ments - 

Heat-equiva- 
lent of  work 

Total  for  work 
experiments 

2,262 
4.225 

451 
4,676 

106-3 

2317 

58-5 
290-2 

104.4 

235-6 

56-8 

292-4 

98-3 
ii8-i 

iiS-i 

67-9 
78-4 

78-4 

94-3 
166-6 

194-8 

28-2 
37-5 

27.7 

37-2 

26-1 
15-2 

i8-o 

lO-I 

What  has  been  already  said  in  connection  with  standard  dietaries 
(p.  612)  indicates  that  the  work  of  the  world  might  possibly  be  accom- 
plished as  well  with  a  smaller  transformation  of  energy  in  the  human 
machine,  at  least  in  the  more  prosperous  countries,  and  that  in  the 
body,  as  in  an  engine,  more  careful  '  stoking  '  might  result  in  a  saving 
of  fuel.  It  is  extremely  improbable,  however,  that  any  argument  of 
this  sort  will  have  much  effect  upon  the  deep-rooted  dietetic  habits  of 
mankind. 

In  any  case  it  must  be  carefully  remembered  that  the  question  of 
the  minimum  amount  of  protein  necessary  in  a  permanent  diet  is 
quite  distinct  from  the  question  of  the  minimum  heat  value  of  the  diet 
for  a  man  of  given  body-weight  doing  a  definite  amount  of  work  under 
definite  conditions.  Whether  the  protein  allowance  be  scanty  or  liberal, 
the  total  heat  value  cannot  be  permanently  reduced  below  a  certain 
minimum  depending  on  the  work  done,  the  climate,  and  other  conditions. 


662 


ANIMAL  HEAT 


The  Seats  of  Heat-Production. — We  have  already  recognized  the 
skeletal  muscles  as  important  seats  of  heat-production.  A  frog's 
muscle,  contracting  under  the  most  favourable  conditions,  does  not 
convert  at  most  more  than  one-fourth  or  one-lifth  of  the  energy  it 
expends  into  mechanical  work;  at  least  three-fourths  or  four- fifths 
of  the  energy  appears  as  heat.  The  muscles  of  mammals  and  of 
man  in  the  intact  body  work,  upon  the  whole,  more  economically 
than  the  excised  frog's  muscles  at  their  maximum  efficiency.  Under 
the  best  conditions — that  is.  when  the  work  is  moderate  and  not  too 


I  NUTRIENTS.        CRAMS 


POTENTIAL    ENEftCY,      CALORIES^ 


DIETARY     STANDARDS.        


SUBSISTENCE    DIET  (PLAYFAIR)      ' 


MAN   AT    MODERATE    WORK^OIt) 


MAN    AT    HARD    WORK  (^ATWATER') 


MAN    WITH    MODERATE  EXERCISE  CPLAYFAIRI 


ACTUAL       DIETARIES.. 


.10  00       20  00       aoloo'     ''4000       so  00       6000 


LAWYER.  MUNICH,  GERMANY, 


PHYSICIAN,  MUNICH, GERMANY.     . 


WELL-FED  BLACKSMITH.  ENGLAND. 
GERMAN  SOLDIERS,  PEACE  FOOTING. 
GERMAN   SOLDIERS,  WAR    FOOTING. 


1     U.S.  ARMY     RATION. 


■■■■i^f^'^^seH 

[■  '■    ;■ 

«'.'  V- 

■, \ 1 

■IBiiHI 

lijljii^^^«^ 


^^nn 


lii 


II 


Fig.  214. — Diagram   showing    the    Heat-equivalent    of  various   Dietaries. 
A,  proteins;  B,  fats;  C,  carbo-hydrates;  D,  heat-equivalent. 


rapidly  done — about  one-third  of  the  chemical  energy  expended 
may  be  transformed  into  mechanical  work,  and  only  two-thirds  into 
heat  (Zuntz).  In  hard  work  three-quarters  of  the  energy  may  be 
changed  into  heat;  but  even  then  the'- efficiency  of  the  muscles  far 
outstrips  that  of  the  best  steam-engines,  which  convert  only  an 
eighth  of  the  total  energy  into  work. 

Notwithstanding  the  splendid  efficiency  of  the  muscular  machine, 
the  gaseous  metabolism  easily  rises  during  muscular  work  to  five 
times,  and  in  severe  labour  to  nine  times  its  resting  value,  although 
persons  inured  to  toil   work   more  economically  than  amateurs. 


INCOME  AND  EXPENDITURE  OF  ENERGY  663 

In  one  of  Atwater's  '  severe  work  '  experiments  the  work  done  in 
twenty-four  hours  had  a  heat-equivalent  of  1,482  calories  (equal  to 
over  630,000  kilogramme-metres).  The  total  heat-production  (in- 
cluding the  equivalent  of  the  work)  was  9,314  calories.  It  is  not 
difficult  to  show  that  the  greater  part  of  the  metabolism  and  heat- 
production  of  a  man  doing  ordinary  work  is  accounted  for  by  the 
contraction  of  the  voluntary  and  involuntary  muscles. 

Even  in  muscles  completely  at  rest  metabolism  goes  on,  and  some 
heat  is  produced.  In  resting  frogs,  newts,  and  snakes,  the  rate  of  heat- 
production  per  gramme  of  tissue  is  about  0-5  gramme-calorie  per  hour 
with  a  room  temperature  of  20°  C,  or  about  a  third  of  that  of  a  resting 
man  (Hill).  Of  course,  this  must  be  above  the  heat-production  of 
muscles  of  these  poikilothermal  animals  absolutely  at  rest.  For  not 
only  must  the  active  heart  and  glands  contribute  sonaething,  but  the 
muscles  of  frogs  lying  huddled  in  a  raicro-calorimeter  not  only  maintain 
the  normal  tonus,  but  are  certainly  liable  to  contract  actively  from 
time  to  time.  By  analyzing  the  gases  of  the  arterial  and  venous  blood, 
Zuntz  compared  the  oxygen  consumption  and  carbon  dioxide  produc- 
tion in  the  hind-legs  of  dogs  when  the  sciatic  and  anterior  crural  nerves 
were  divided  and  intact.  In  both  cases  the  muscles  were  at  rest  in 
the  ordinary  sense.  But  in  the  second  experiment  the  central  '  tonus  ' 
(p.  889)  was  preserved,  while  in  the  first  it  was  abolished.  In  one 
experiment  in  which  the  nerves  were  intact  the  oxygen  consumed 
amounted  to  i'22  c.c,  and  the  carbon  dioxide  produced  to  1-32  c.c, 
per  kilo  of  tissue  per  minute.  In  the  experiment  in  which  the  nerves 
were  severed,  the  corresponding  numbers  were  0'68  c.c.  for  the  oxygen, 
and  0-63  c.c.  for  the  carbon  dioxide.  Although  it  is  probable,  from 
the  results  of  Chauveau  and  Kauffmann  already  referred  to  (p.  266), 
that  these  figures  are  too  low  for  the  normal  resting  muscle,  they  still 
demonstrate  that,  even  in  the  absence  of  innervation  from  the  central 
nervous  system,  the  metabolism,  and  therefore  the  heat-production  of 
the  muscles,  are  by  no  means  negligible;  0'68  c.c.  of  oxygen  per  minute 
corresponds  to  40-8  c.c.  per  hour,  or  more  than  one-tenth  of  the  oxygen 
consumption  per  kilo  per  hour  of  a  fasting  dog  lying  at  rest  (Zuntz). 

If  the  work  of  the  heart  is  taken  as  16,600  kilogramme-metres  in 
twenty-four  hours  (p.  138),  the  total  heat  produced  by  this  organ  will 
be  equivalent  (on  the  assumption  that  it  converts  one-third  of  its 
energy  into  work)  to  about  50,000  kilogramme-metres,  or  not  much 
less  than  120  calories,  since,  practically,  the  whole  work  is  expended 
in  overcoming  the  friction  of  the  vessels,  and  finally  appears  as  heat. 
Enough  energ\'  is  transformed  in  twenty-four  hours  in  the  heart  of  the 
colonel  of  a  regiment  of  1,000  men  to  lift  the  whole  regiment  to  the 
height  of  the  mess-table,  if  it  could  be  all  changed  into  mechanical 
work.  Barcroft  and  Dixon  have  calculated  the  energy  of  the  heart's 
contraction  on  the  assumption  that  it  is  derived  from  the  oxidation 
of  a  carbo-hydrate  by  the  oxygen  absorbed  by  the  organ.  They  con- 
cluded that  the  energy  set  free  in  the  heart  01  a  dog  weighing  12  kilos 
corresponds  on  the  average  to  7*86  kilogramme-metres  per  minute, 
which  is  equivalent  to  26*6  calories  in  twentj'-four  hours.  Allowing  for 
the  fact  that  the  heart  of  a  small  animal  pumps  more  blood  in  propor- 
tion to  the  body-weight  than  the  heart  of  a  large  animal  (p.  139).  this 
result  agrees  very  well  with  that  deduced  from  the  work  of  the  heart. 
The  work  of  the  inspiratory  muscles  may  be  reckoned  at  13,000  kilo- 
gramme-metres, equal  to  30'5  calories,  and  the  heat  produced  by  them 


664  ANIMAL  HEAT 

at,  say,  90  calories.  In  sum,  the  muscular  work  of  the  circulation  and 
respiration  is  responsible  for  the  production  of  about  210  calories 
(without  including  the  heat  produced  by  the  smooth  muscle  of  the 
bronchi  and  bloodvessels),  or  nearly  one-twelfth  of  the  total  produc- 
tion of  a  man  doing  ordinary  labour. 

The  glands,  and  then  the  central  nervous  system,  rank  after  the 
muscles,  though  at  a  great  distance,  as  seats  of  heat-production. 
The  liver  and  brain  (?)  are  the  hottest  organs  in  the  body;  and  that 
this  is  not  altogether  due  to  their  being  well  protected  against  loss 
of  heat  is  shown,  in  the  case  of  the  liver,  by  the  excess  of  tempera- 
ture of  the  blood  of  the  hepatic  over  that  of  the  portal  vein.  In 
view,  however,  of  the  exaggerated  importance  which  some  have 
given  to  these  organs  as  foci  of  heat-production,  it  may  be  well  to 
point  out  that  although  many  of  the  chemical  changes  in  the  animal 
body  are  undoubtedly  associated  with  the  setting  free  of  heat 
(exothermic  reactions),  other,  and  not  less  weighty  and  character- 
istic, reactions  may  cause  the  absorption  of  heat  (endothermic 
reactions) ;  and  it  is  possible  that  some  of  the  syntheses  which  many 
of  the  tissues  are  capable  of  performing  may  be  included  in  this 
latter  category.  For  example,  when  urea  is  decomposed  so  as  to 
yield  ammonium  carbonate  (p.  472),  heat  is  set  free.  We  must 
assume  that  if  ammonium  carbonate  were  transformed  into  urea  in 
the  liver,  an  equal  amount  of  heat  would  be,  on  the  whole,  absorbed. 
So  that  the  heat-production  of  an  organ  may  depend,  not  only  upon 
the  quantity,  but  also  upon  the  quality,  of  its  chemical  activity. 
In  all  the  tissues,  including  the  nuiscles,  it  is  necessary  to  assume 
that  some  of  the  energy  transformed  is  expended  in  so-called  '  resti- 
tution '  processes — that  is,  in  replenishing  the  store  of  nutritive 
material  within  the  cells  and  in  building  up  the  protoplasm.  Claude 
Bernard  observed  an  excess  of  06°  C  in  the  temperature  of  the 
blood  of  the  hepatic  vein  over  that  of  the  portal  during  hunger,  and 
as  much  as  i'6°  at  the  height  of  digestion,  although  at  the  beginning 
of  digestion  the  portal  blood  was  the  hotter  by  04°.  But  such 
observations,  like  the  corresponding  ones  on  the  salivary  glands,  are 
open  to  many  errors,  and  when  we  consider  the  enormous  tide  of 
blood  which  during  digestion  sets  through  the  portal  system,  we 
shall  look  with  suspicion  upon  results  that  announce  a  difference 
of  more  than  a  small  fraction  of  a  degree  in  the  temperature  of  the 
incoming  and  outgoing  blood  of  the  liver.  Probably  not  less  than 
200  litres  of  blood  pass  in  twenty-four  hours  through  the  liver  of  a 
2-kilo  rabbit.  If  the  temperature  of  this  blood  is  raised  even  one- 
tenth  of  a  degree  in  its  passage  through  the  hepatic  capillaries,  this 
would  correspond  to  a  heat-production  of  20,000  small  calories,  or 
one-tenth  of  the  whole  heat  produced  in  the  animal. 

In  the  case  of  the  brain  there  is  some  evidence,  obtained  by  com- 
parison of  the  gases  of  blood  taken  from  the  carotid  and  from  the  venous 
sinuses  (torcula  Heropliili),  that  the  metabolism  is  feeble  as  compareid 


THERMOTAXIS  665 

even  with  that  of  resting  muscles  (Hill).  Nor  is  it  possible  to  demon- 
strate any  marked  or  constant  increase  when  the  cerebral  cortex  is 
roused  to  such  an  active  discharge  of  impulses  as  leads  to  general 
epileptiform  convulsions.  The  rise  of  temperature  of  certain  regions, 
especially  the  occipital  portion,  of  the  scalp,  which  some  observers  have 
stated  to  take  place  during  mental  activity,  cannot  be  due  to  con- 
duction of  heat  from  the  brain  through  the  skull.  It  might  be  caused 
by  vaso-motor  changes  in  the  scalp,  associated  with  corresponding  • 
changes  in  related  areas  of  the  cortex.  The  alleged  increase  in  the 
temperature  of  the  brain  during  intense  psychical  activity,  sometimes 
to  0'2°  C,  or  0-3°  C.  above  the  rectal  temperature  (Mosso),  may  also, 
if  genuine,  be  due  to  vascular  changes.  And  if  we  remember  how 
large  a  proportion  of  the  central  nervous  system  is  made  up  of  nerve- 
fibres,  in  which  no  sensible  production  of  heat  has  ever  been  demon- 
strated, it  will  not  appear  surprising  if  even  a  considerable  increase 
in  the  metabolism  of  the  really  active  elements  should  fail  to  make 
itself  felt. 

Section  III. — ^Regulation  of  Temperature  or  Therm otaxis 

What,  now,  is  the  mechanism  by  which  the  balance  is  maintained 
in  the  homoiothermal  animal  between  heat-production  and  heat- 
loss  ?  In  answering  this  question  we  have  to  recognize  that  both 
of  these  quantities  are  variable,  that  a  fall  in  the  production  of  heat 
may  be  compensated  by  a  diminution  of  heat-loss,  and  an  increase 
in  the  loss  of  heat  balanced  by  a  greater  heat-production. 

The  loss  of  heat  from  the  surfaces  of  the  body  may  be  regulated 
both  by  involuntary  and  by  voluntary  means.  It  is  greatly  affected 
by  the  state  of  the  cutaneous  vessels,  and  these  vessels  are  under  the 
influence  of  nerves.  A  cold  skin  is  pale,  and  its  vessels  are  con- 
tracted. In  a  warm  atmosphere  the  skin  is  flushed  with  blood,  its 
vessels  are  dilated,  its  temperature  is  increased;  an  effort,  so  to 
speak,  is  being  made  by  the  organism  to  maintain  the  difference  of 
temperature  between  its  surface  and  its  surroundings  on  which  the 
rate  of  heat-loss  by  radiation  and  conduction  depends.  A  still 
more  important  factor  in  man,  and  in  animals  hke  the  horse,  which 
sweat  over  their  whole  surface,  is'  the  increase  and  decrease  in  the 
quantity  of  water  evaporated  and  of  heat  rendered  latent.  It  is 
owing  to  the  wonderful  elasticity  of  the  sweat-secreting  mechanism, 
and  to  the  increase  of  respiratory  activity  and  the  consequent 
increase  in  the  amount  of  watery  vapour  given  off  by  the  lungs, 
that  men  are  able  to  endure  for  days  an  atmosphere  hotter  than  the 
blood,  and  even  for  a  short  time  a  temperature  above  that  of  boiling 
water.  The  temperature  of  a  Turkish  bath  may  be  as  high  as 
65°  to  80°  C.  Blagden  and  Fordyce  exposed  themselves  for  a  few- 
minutes  to  a  temperatiu-e  of  nearly  127°  C  Although  meat  was 
being  cooked  in  the  same  chamber  by  the  heat  of  the  air,  they 
experienced  no  ill-effects,  nor  was  their  body-temperature  even 
increased.     But  a  far  lower  temperature  than  this,  if  long  con- 


666  ANIMAL  HEAT 

tinned,  is  dangerous  to  life.  During  the  '  hot  waves  '  not  infre- 
quently experienced  in  summer  in  the  United  States,  hundreds  of 
persons  have  died  within  a  few  days  from  the  excessive  heat.  It  is 
stated  that  during  the  unusually  hot  summer  of  1819  the  tempera- 
ture at  Bagdad  ranged  for  a  considerable  time  between  108°  and 
120°  F.  (42°  to  49°  C),  and  there  was  great  mortality.  A  much 
higher  temperature  may  be  borne  in  dry  air  than  in  air  saturated 
with  watery  vapour.  A  shade  temperature  of  100°  F.  (377°  C.)  in 
the  dry  air  of  the  South  African  plateaux  is  quite  tolerable,  while  a 
temperature  of  85°  F.  (29-4°  C)  in  the  moisture-laden  atmosphere 
of  Bombay  may  be  oppressive.  The  reason  is  that  in  dry  air  the 
sweat  evaporates  freely  and  cools  the  skin,  while  in  moist  air, 
although  according  to  Rubner  the  loss  of  heat  by  radiation  and 
conduction  is  increased,  the  loss  of  heat  by  evaporation  of  sweat  is 
diminished  in  a  still  greater  degree.  In  saturated  air  at  the  body- 
temperature  no  loss  of  heat  by  perspiration  or  by  evaporation  from 
the  pulmonary  surface  is  possible;  the  temperature  of  an  animal  in 
a  saturated  atmosphere  at  35°  to  40°  C  soon  rises,  and  the  animal 
dies.  In  animals  Hke  the  dog,  which  sweat  little  or  not  at  all  on 
the  general  surface,  the  regulation  of  the  heat-loss  by  respiration  is 
relatively  more  important  than  in  man. 

The  observations  of  Boycott  and  Haldane  in  a  deep  mine,  in  the 
incubating-room  of  a  laboratory,  and  in  a  Turkish  bath  illustrate  the 
important  influence  of  the  humidity  of  the  air.  In  still  air  the  body- 
temperature  rose  above  normal  when  the  wet-bulb  thermometer  rose 
above  31*  C.  (88°  F.),  and  it  remained  normal  whatever  the  external 
temperature  might  be  so  long  as  the  reading  of  the  wet-bulb  thermo- 
meter did  not  exceed  that  level.  The  more  the  wet-bulb  thermometer 
rose  above  31'  the  more  rapid  was  the  increase  in  the  body-temperature. 
In  moving  air  a  greater  degree  of  humidity  could  be  borne  without 
increase  in  the  body-temperature,  which  did  not  occur  till  the  tem- 
perature shown  by  the  wet-bulb  thermometer  exceeded  35°  C.  The 
great  increase  in  the  evaporation  of  sweat  when  the  temperature  of  the 
air  is  high  is  shown  by  the  observation  that  on  a  warm  day  (dry  bulb, 
79°  F. ;  wet  bulb,  6j'^°  F.)  the  average  loss  of  moisture  from  the  body 
was  1,816  grammes  for  four  soldiers  during  a  march  of  seven  miles, 
while  on  a  cold  day  (dry  bulb,  45*  F. ;  wet  bulb,  38°  F.)  it  was  only 
419  grammes  during  the  same  march  by  the  same  men  (Pembrey). 

The  winter  fur  of  Arctic  animals  is  a  special  device  of  Nature  to 
meet  the  demands  of  a  rigorous  climate,  and  combat  a  tendency  to 
excessive  loss  of  heat.  The  experiments  of  Hosshn,  and  the  experi- 
ence of  squatters  in  AustraUa,  go  to  show  that  even  domesticated 
animals  have  a  certain  power  of  responding  to  long-continued 
changes  in  external  temperature  by  changes  in  the  radiating  surfaces 
which  affect  the  loss  of  heat.  It  is  said  that  in  the  hot  plains  of 
Queensland  and  New  South  Wales  the  fleeces  of  the  sheep  show  a 
tendency  to  a  progressive  decrease  in  weight.  And  Hosslin  found 
that  a  young  dog  exposed  for  eighty-eight  days  to  a  temperature 


TH  ERMO  TA  XI S  667 

of  5°  C.  developed  a  thick  coat  of  fine  woolly  hairs.  Another  dog 
of  the  same  Utter,  exposed  for  the  same  length  of  time  to  a  tem- 
perature of  31-5°  to  32°  C,  had  a  much  scantier  covering.  The 
increased  protection  against  heat-loss  in  the  case  of  the  '  cooled  ' 
dog  was  not  sufficient  fully  to  compensate  for  the  lowered  external 
temperature.  The  metabolism — that  is  to  say,  the  heat-production 
— was  also  increased.  And  although  the  food  was  exactly  the  same 
for  both  animals  in  quantity  and  quality,  the  dog  at  5°  C.  put  on 
less  than  half  as  much  fat  in  the  period  of  the  experiment  as  the 
'  heated  '  dog,  but  the  same  amount  of  '  flesh.' 

The  voluntary  factor  in  the  regulation  of  the  heat-loss  is  of  great 
importance  in  man.  Clothes,  like  hair  and  other  natural  coverings, 
retard  the  loss  of  heat  from  the  skin  chiefly  by  maintaining  a  zone 
of  still  air  in  contact  with  it,  for  air  at  rest  is  an  exceedingly  bad 
conductor  of  heat.  A  man  clothed  in  the  ordinary  way  has  two  or 
three  concentric  air-jackets  around  him.  The  air  in  the  intervals 
between  the  inner  and  outer  garments  is  of  importance  as  well  as 
that  in  the  pores  of  the  clothes  themselves;  and  it  is  for  this  reason 
that  two  thin  shirts  put  on  one  above  the  other  are  warmer  than  the 
same  amount  of  material  in  the  form  of  a  single  shirt  of  double 
thickness.  When  a  man  feels  himself  too  hot  and  throws  off  his 
coat,  he  really  removes  one  of  the  badly  conducting  layers  of  air, 
and  increases  the  rate  of  heat-loss  by  radiation  and  conduction. 
At  the  same  time  the  water-vapoiir,  which  practically  saturates 
the  layer  of  air  next  the  skin,  is  allowed  a  freer  access  to  the  surface, 
and  the  loss  of  heat  by  the  evaporation  of  the  sweat  becomes  greater. 
The  power  of  voluntarily  influencing  the  heat-loss  must  be  looked 
upon  in  man  as  one  of  the  most  important  means  by  which  the 
equihbrium  of  temperature  is  maintained.  In  the  lower  animals 
this  powei  also  exists,  but  to  a  much  smaller  extent.  A  dog  on  a 
hot  day  puts  out  its  tongue  and  stretches  its  limbs  so  as  to  increase 
the  surface  from  which  heat  is  radiated  and  conducted.  The  mere 
placing  of  a  rabbit  on  its  back,  with  its  legs  apart,  may  cause  in  an 
hour  or  two  a  fall  of  1°  to  2°  C.  in  the  rectal  temperature.  The 
power  of  covering  themselves  vnth  straw  or  leaves,  of  burrowing 
and  of  forming  nests,  ma}-  be  included  among  the  voluntary  means 
of  regulation  of  the  heat-loss  possessed  by  animals.  A  man  opens 
the  window  when  he  is  too  hot,  and  pokes  the  fire  when  he  feels 
cold.  Both  actions  are  a  tribute  to  his  status  as  a  homoiothermal 
animal,  and  illustrate  the  importance  of  the  voluntary  element  in 
the  mechanism  by  which  his  temperature  is  controlled. 

The  production  of  heat,  like  the  loss,  is  to  a  certain  extent  under 
voluntary  control.  Rest,  and  especially  sleep,  lessen  the  pro- 
duction; work  increases  it.  The  inhabitants  of  the  tropics,  human 
and  brute,  often  tide  over  the  hottest  part  of  the  day  by  a  siesta; 
and  it  is  as  natural,  and  as  much  in  accordance  with  physiological 


668  ANIMAL  HEAT 

laws,  that  a  man  overpowered  by  the  heat  should  lie  down,  as  it  is 
that  he  should  walk  about  and  stamp  his  feet  or  clap  his  hands  on 
a  cold  winter  morning.  In  the  one  case  a  diminution,  in  the  other 
an  increase,  in  the  heat-production  is  aimed  at  by  a  corresponding 
change  in  the  amount  of  muscular  contraction.  The  quantity  and 
quality  of  the  food  also  influence  the  production  of  heat.  The 
Eskimo,  who  revels  in  train-oil  and  tallow-candles,  unconsciously 
illustrates  the  experimental  fact  that  the  heat  of  combustion  of  fat 
is  high;  the  rice  diet  of  the  ryot  of  the  Carnatic,  with  its  low  heat- 
equivalent,  seems  peculiarly  adapted  to  the  dweller  in  tropical 
lands.  But  it  would  be  easy  to  attach  too  much  weight  to  con- 
siderations such  as  these.  The  Arctic  hunter  eats  animal  fat,  and 
the  Indian  peasant  vegetable  carbo-hydrate,  not  only  because  fat 
has  a  high  and  carbo-hydrate  a  low  heat-equivalent,  but  because 
in  the  climate  of  the  Far  North  animals  with  a  thick  coating  of 
badly-conducting  fat  are  plentiful,  and  vegetable  food  scarce; 
whereas  in  the  river-valleys  of  India  Nature  favours  the  growth  of 
rice,  and  religion  forbids  the  killing  of  the  sacred  cow. 

The  production  of  heat  is  also  controlled  by  an  involuntary  nervous 
mechanism,  through  which  the  '  chemical  '  regulation  of  the  body- 
temperature  is  achieved,  as  the  '  physical '  regulation  is  accom- 
plished by  the  nervous  mechanisms  that  control  the  circulation, 
the  sweat-glands,  and  the  respiratory  movements.  It  is  a  matter 
of  everyday  experience  that  cold  causes  involuntary  shivering — 
involuntary  muscular  contractions — the  object  of  which  seems  to  be 
a  direct  increase  in  the  heat-production.  But  besides  this  visible 
mechanical  effect,  the  application  of  cold  to  a  warm-blooded  animal, 
when  not  carried  so  far  as  to  greatly  reduce  the  rectal  temperature, 
is  accompanied  by  a  marked  increase  in  the  metabolism,  as  shown 
by  an  increased  production  of  carbon  dioxide  and  consumption  of 
oxygen.  In  cold-blooded  animals  like  the  frog  the  metabolism, 
on  the  other  hand,  rises  and  falls  with  the  external  temperature; 
there  is  no  automatic  mechanism  which  answers  an  increased  drain 
upon  the  stock  of  heat  in  the  body  by  an  increased  supply.  Or,  in 
the  light  of  recent  experiments,  we  ought  rather  to  say  that, 
although  the  rudiments  of  a  heat-regulating  mechanism  may  exist 
in  such  animals  as  the  frog,  the  newt,  and  even  the  earthworm 
(Vernon),  it  is  only  able  to  modify  to  a  certain  extent  the  effects  of 
changes  of  external  temperature,  not  to  balance  or  even  override 
them,  as  in  the  homoiothermal  animal.  In  resting  frogs  and  snakes 
the  rate  of  heat-production,  as  measured  by  the  micro-calorimeter, 
increases  two  to  three  times  when  the  temperature  rises  io°  C. 
(Hill).  The  warm-blooded  animal  loses  its  heat-regulating  power 
when  a  dose  of  curara  sufficient  to  paralyze  the  voluntary  muscles 
is  given.  A  curarized  rabbit,  kept  alive  by  artificial  respiration, 
reacts  to  changes  of  external  temperature  like  the  cold-blooded 
frog.     Now,  the  only  action  of  curara  adequate  to  account  for  this 


THBRMOTAXIS  669 

effect  is  its  power  of  paralyzing  the  motor  innervation,  and  so 
cutting  off  from  the  skeletal  muscles  impulses  which  in  the  intact 
animal  would  have  reached  them.  The  excitation  by  cold  of  the 
cutaneous  nerves,  or  some  of  them,  which  in  the  unpoisoned  animal 
is  reflected  along  the  motor  nerves  to  the  muscles,  and  causes  the 
increase  of  metaboUsm,  is  now  blocked  at  the  end  of  the  motor 
path;  and  the  muscles,  the  great  heat-producing  tissues,  are  aban- 
doned to  the  direct  influence  of  the  external  temperature  (Pfliiger). 
How  is  it,  then,  that  nervous  impulses  from  the  skin  produce  in 
the  intact  animal  their  effect  upon  the  chemical  processes  in  the 
muscles  ?  We  know  that  the  heat-production  of  a  muscle  is  greatly 
increased  when  it  is  caused  to  contract;  but  it  has  not  hitherto  been 
possible  by  artificial  stimulation  to  demonstrate  that  any  chemical 
or  physical  effect  is  produced  in  a  muscle  by  excitation  of  its  motor 
nerve  unless  as  the  accompaniment  of  a  mechanical  change.  When 
the  gastrocnemius  of  a  frog  poisoned  with  not  too  large  a  dose  of 
curara  is  laid  on  a  resistance  thermometer  (p.  757),  and  its  nerve 
stimulated  from  time  to  time  as  the  curara  paralysis  deepens, 
heating  of  the  muscle  is  observed  as  long  as,  and  only  as  long  as, 
there  is  any  visible  contraction.  The  gaseous  metabolism  of  a 
rabbit  immersed  in  a  bath  of  constant  temperature  may  sink  by 
as  much  as  30  to  40  per  cent,  when  curara  is  given.  One  obvious 
cause  of  this  is  the  complete  muscular  relaxation.  And  the  whole 
secret  of  the  regulation  of  the  heat-production  might  be  plausibly 
supposed  to  lie  in  the  bracing  effect  of  cold  upon  the  skeletal  muscles 
and  the  relaxing  effect  of  heat.  Indeed,  in  man  it  has  been  observed 
that  exposure  to  moderate  cold  causes  no  metabohc  increase  when 
shivering  is  prevented  by  a  strong  effort  of  the  will  (Loewy). 
Nevertheless,  the  explanation  is  inadequate  in  the  case  of  small 
animals,  such  as  guinea-pigs,  rabbits,  and  cats;  for  very  great 
changes  in  the  metabolism  may  be  brought  about  by  external  cold 
without  any  outward  token  of  increased  muscular  activity.  In  a 
man  also  a  fall  in  the  external  temperature  from  23°  to  15°  C.  caused 
a  certain  increase  in  the  output  of  carbon  dioxide  (from  27  9  to 
323  grammes  per  hour),  although  no  shivering  was  observed.  As 
the  temperature  of  the  air  is  lowered,  the  point  is  soon  reached  at 
which  shivering  can  no  longer  be  suppressed,  and  then  it  is  neither 
practicable  nor  perhaps  very  important  to  distinguish  clearly  the 
portion  of  the  increased  heat-production  associated  with  the  visible 
muscular  contractions  and  the  portion  due  to  quickened  muscular 
metabolism  without  contraction.  Lefevre  found  that  in  man  a 
marked  increase  in  the  heat-loss,  such  as  is  caused  by  immersion 
for  a  considerable  time  (one  to  three  hours)  in  cold  water  (at  a  tem- 
perature of  7"^  to  15°  C),  was  accompanied  by  a  great  increase  in 
the  production  of  heat,  so  that  the  axillary  temperature  fell  com- 
paratively little — e.g.,  only  1°  C.  during  a  stay  of  three  hours  in  a 
bath  at  15°  C.     With  short  periods  of  immersion,  a  characteristic 


670  ANIMAL  HEAT 

reaction  occurs  after  the  person  comes  out  of  the  bath.  The  rectal 
temperature  falls  to  a  minimum,  which  is  reached  in  twenty  to 
thirty  minutes  after  exit  from  the  bath,  and  then  gradually  returns 
to  normal.  This  fall  of  internal  temperature  is  due  to  the  heating 
of  the  superficial  portions  of  the  body  at  the  expense  of  the  central 
portions.  By  training,  the  fall  of  temperature  is  greatly  lessened, 
the  heat-regulating  mechanism  acquiring,  so  to  speak,  with  practice, 
greater  promptitude  and  precision  of  adjustment. 

It  must  be  admitted,  then,  that — especially  in  the  smaller  homoio- 
thermal  animals — the  metabolic  changes  normally  going  on  in  the 
resting  muscles  may  be  refiexly  increased  without  the  usual  accom- 
paniment of  mechanical  contraction,*  and  that  such  an  increase  of 
'  chemical  tone  '  is  an  important  means  by  which  the  temperature 
is  regulated.  It  is  possible  that  other  organs  besides  the  muscles 
may  be  concerned,  though  not  to  a  sufficient  extent  to  secure  the 
due  regulation  of  temperature  during  curara  paralysis.  It  is 
obvious  that  in  man,  whose  environment  is  so  much  under  his  own 
control,  a  mere  automatic  regulation  is  less  required  than  in  the 
inferior  anhnals,  and  that  a  regulative  power,  if  present  in  rudiment, 
would  tend  to  '  atrophy  '  by  disuse,  or,  at  all  events,  to  become  less 
sensitive  to  slight  changes  of  temperature.  In  the  larger  animals, 
again,  mere  bulk  is  an  important  safeguard  against  any  sudden 
change  of  internal  temperature.  To  reduce  the  temperature  of  a 
horse  or  an  elephant  by  1°,  a  considerable  quantity  of  heat  must 
be  lost,  while  a  very  slight  loss  would  suffice  to  cool  a  mouse  by 
that  amount.  Not  only  so,  but  the  surface  by  which  heat  is  lost  is 
greater  in  proportion  to  the  mass  of  the  body  in  small  than  in  large 
animals.  The  power  of  rapidly  increasing  the  heat-production  to 
meet  a  sudden  demand  is,  therefore,  far  more  important  to  the 
mouse  thian  to  the  horse;  and  the  fact  (p.  616)  that  the  metabolism 
of  an  animal  varies  approximately  as  its  surface,  and  not  as  its 
mass,f  is  an  illustration  of  the  nice  adjustment  by  which  heat- 
equilibrium  is  maintained.  There  is  reason  to  believe  that  at  a 
temperature  equal  to  that  of  the  human  body  the  heat-production 
of  a  frog  per  unit  of  mass  would  equal  that  of  a  man  or  other  large 
mammal,  although  it  would  be  far  less  than  that  of  a  small  homoio 

*  Increased  tonus  of  the  muscles  might,  however,  account  for  a  portion 
of  the  increased  heat-production. 

f  The  relation  between  mass  ^M)  and  surface  (S)  in  man  is  approximately 
given  by  the  equation  ---^—  =  K,   and  the    relation  between  surface,  mass, 

length  of  body  (L),  and  circumference  of  chest  (C)  just  above  the  nipples  in 

S\/M*.L*.C2 
the  '  mean  '  position  of  respiration,  by  the  equation   — „  j  „" —  =  K'.     M  is 

expressed  in  grammes,  S  in  square  centimetres,  L  and  C  in  centimetres.  K  is 
a  constant  whose  mean  value  is  123,  and  K'  a  constant  whose  mean  value  is 
45  (Meeh). 


THERMOTAXIS 


071 


thermal  animal.  This  is  in  favour  of  the  view  that  in  the  larger 
mammals  a  nervous  regulation  of  the  intensity  of  the  metabolism 
is  not  of  prime  importance. 

Relations  between  Heat-Production,  Surface  Area,  and  Blood-Flow.— 
The  following  table  shows  how  close  is  the  agreement  in  the  heat- 
production  per  unit  of  surface  calculated  by  the  formula  for  animals  of 
different  species  and  very  different  body-weight: 


Weieht  in 
Kilos. 

Calories  produced  in  24  Hours. 

Per  Kilo. 

Per  .Sq.  Metre 
of  Surface. 

948 
1,042 
1,036 

917 

943 
1,188 

Horse     ----- 
Man 

Dog        -         -         -         -         - 
Rabbit  (without  ears)     - 
Fowl       .         .         -         -         - 
Mouse              _         -         -         - 

441 

64-3 

15-2 

2-3 

2 

0'0i8 

II-3 
32-1 

51-5 
75-1 
71-0 

2I2-0 

The  next  table,  calculated  by  Rubner  from  the  quantity  of  tissue- 
protein  and  fat  consumed,  gives  the  relative  intensity  of  heat-produc- 
tion in  fasting  dogs  of  different  sizes:  and  along  with  it  is  given  for 
comparison  some  of  the  results  on  the  output  of  the  heart  in  dogs  of 
different  weight,  obtained  by  the  method  of  injecting  salt  solution 
into  the  ventricle  described  on  p.  139. 


Weight  in 
Kilos. 

Calories  per  Kilo 
per  Hour. 

Weight  in  Kilos. 

Output  per  Kilo 
per  Second  in  c.c. 

31 

1-58 

27-89 

1-92 

24 

1-70 

18-20 

2-31 

20 

1-87 

12-82 

3-28 

18 

1-92 

11-68 

3-56 

10 

2-55 

10-32 

3-86 

6 

2-84 

7-165 

4-13 

3 

3-78 

4-975 

5-36 

Number  of 
Dogs. 


Range  of  Weight  in 
Kilos. 


34-5  to  27-9 

i8-2  ,,  11-7 

10-3  ..     9-3 

8-4  ..     7-2 

6-5  ••     5-0 


Average  Weight. 


31-5 
14-3 

9-8 
7-8 


.Average  Output 
per  Second  in  c.c. 

75-7 
46-6 

34-8 
28-8 
25-2 

Average  Output 

per  Kilo  per 

Second. 


2-40 
3-25 

3'55 
3-69 
4-42 


It  is  obvious  that  the  two  quantities,  heat-production  (or  loss)  and 
heart-output,  vary  in  the  same   general   way.     The  reason  is  clear. 


672  ANIMAL  HEAT 

Oxygen  must  be  absorbed  by  the  lungs  in  proportion  to  the  heat 
produced,  and  where  more  oxygen  is  to  be  absorbed,  more  blood  passes 
through  the  lungs  to  take  it  up.*  It  is  interesting  to  inquire  whether 
in  the  smaller  animals  the  contact  of  the  alveolar  air  with  the  rela- 
tively increased  quantity  of  blood  is  obtained  by  a  similar  increase  in 
the  area  covered  by  capillaries  (or  in  what  is  doubtless  approximately 
proportional  to  this  area,  the  mass  of  the  lung  tissue),  or  by  a  shortening 
of  the  pulmonary  circulation  time  (p.  137).  The  answer  is  that  the  pul- 
monary circulation  time  is  markedly  shortened  as  the  size  of  the 
animal  diminishes,  although  not  in  proportion  to  the  diminution  in 
weight,  but  rather  in  proportion  (roughly  speaking)  to  the  square  root 
of  the  surface.  This  could  not  be  the  case  if  the  area  of  the  pulmonary 
surface  bore  the  same  proportion  to  the  area  of  the  skin  as  the  output 
of  the  heart  does.  For  in  this  case  the  vascular  capacity  of  the  lungs 
(or  the  quantity  of  blood  contained  in  them)  would  be  proportional  to 
the  heart  output,  and  the  time  required  for  the  blood  discharged  by 
the  right  ventricle  to  displace  the  whole  of  the  blood  contained  in  the 
lungs  at  any  given  moment — that  is  to  say,  the  average  pulmonary 
circulation  time — would  be  the  same  for  animals  of  all  sizes.  But  it 
may  very  well  be  the  case  if  the  vascular  capacity  of  the  lungs,  (or 
the  mass  of  the  lung  tissue)  decreases  more  rapidly  than  the  surface 
decreases,  say  in  proportion  to  the  body-weight.  At  first  thought  it 
might  appear  advantageous  that  the  area  of  the  surface  through  which 
oxygen  is  absorbed  should  be  proportional  to  the  area  through  which 
the  heat  produced  in  the  oxidations  of  the  body  is  chiefly  eliminated, 
so  that  the  greater  the  necessary  heat  loss,  the  greater  should  be  the 
facilities  for  absorption  of  oxygen.  We  have,  however,  already  seen 
(p.  250)  that  the  blood,  even  when  it  passes  through  the  pulmonary 
capillaries  at  its  maximum  speed,  has  still  sufficient  time  to  practically 
saturate  itself  with  oxygen.  Within  the  limits  where  this  holds  good 
there  would  be  no  advantage  in  increasing  the  relative  size  of  the 
lungs  rather  than  in  increasing  the  linear  velocity  of  the  blood  passing 
through  them — that  is,  diminishing  the  pulmonary  circulation  time — 
and  on  general  principles  it  may  be  assumed  that  a  larger  pulmonary 
reservoir  than  is  necessary  for  the  maximum  possible  intake  of  oxygen 
would  not  be  provided.  For  if  the  pulmonary  reservoir  holds  an  ex- 
cessive amount  of  blood,  some  other  tissues  must  have  too  little.  It 
has  been  stated,  indeed,  that  in  animals  of  different  size  in  the  same 
species  the  total  quantity  of  blood  in  the  body  is  a  function  not  of  the 
body- weight,  but  of  the  surface,  so  that  the  smaller  animals  have 
a  relatively  larger  amount  of  blood  (p.  56).  If  this  be  so,  it  is  probably 
related  to  the  greater  intensity  of  metabolism  and  the  greater  loss  of 
heat  from  the  surface  of  small  animals,  which  entails  a  greater  cir- 

*  For  simplicity,  the  possibility  that  the  coefficient  of  utilization  of  the  oxy- 
gen-carrying capacity  of  the  blood  (i.e..  the  quantity  of  oxygen  absorbed  by 
a  litre  of  blood  during  its  passage  through  the  lungs  divided  by  the  total 
quantity  of  oxygen  which  it  can  take  up)  may  vary,  is  disregarded.  This 
possibility  woukl  imply  that  the  average  oxygen  content  of  the  venous  blood 
coming  to  the  right  side  of  the  heart  varied  in  animals  of  different  size,  more 
oxygen  being  abstracted,  for  example,  from  the  blood  in  passing  through  the 
tissues  of  small  animals  than  of  large.  The  greater  the  utilization  of  the 
oxygen  the  smaller  would  the  quantity  of  blood  passing  through  the  lungs 
require  to  be.  There  is  no  evidence,  however,  that  such  differences  exist  be- 
tween animals  of  the  same  species  of  different  size,  although  it  has  been  sug- 
gested that  a  higher  coefficient  of  utilization  coupled  with  a  proportionately 
smaller  heart  output  may  be  one  way  in  which  training  diminishes  the  diffi- 
culty and  discomfort  of  hard  muscular  effort. 


THERMOTAXIS  673 

culation  through  the  skin.  Tliis  greater  cutaneous  circulation  means 
the  permanent  withch-awal  of  blood  from  the  rest  of  the  body,  which 
c  >-n  be  compensated  by  a  corresponding  increase  in  the  total  circulating 
mass.  The  fact  that  the  blood  contained  in  the  living  skin  must 
form  a  substantial  fi'action  of  the  total  blood,  and  a  fraction  rela- 
tively more  important  in  the  smaller  than  in  the  larger  animals, 
would  of  itself  help  to  establish  a  relation  between  surface  area 
and  total  quantity  of  blood.  The  greater  volume  of  the  blood 
will  contribute  to  the  increased  output  of  the  heart  in  the  smaller 
animals.  In  this  connection  the  fact  already  alluded  to  more  than 
once  may  be  again  emphasized,  that  it  is  not  the  quantity  of  blood  con- 
tained in  an  organ  or  an  organism,  but  the  quantity  passing  through 
the  capillaries  in  a  given  time,  which  is  the  important  thing  for  its 
function,  in  the  case  of  the  lungs  for  the  function  of  the  gaseous  ex- 
change, in  the  case  of  the  skin  for  the  regulation  of  the  heat- loss. 

There  is  reason  to  suppose  that  the  average  amount  of  blood  contained 
in  the  cutaneous  vessels,  as  well  as  the  average  amount  flowing  through 
them  per  unit  of  time,  is  greater  in  proportion  to  the  total  area  of  the 
skin  in  animals  like  man,  with  a  skin  devoid  of  fur  and  well  supplied 
v/ith  sweat  glands,  than  in  animals  well  protected  by  hair  ancl  with 
few  sweat  glands.  For  in  the  latter  the  cutaneous  circulation  cannot 
take  as  great  a  share  in  the  regulation  of  the  heat-loss  as  in  the  former, 
although,  of  course,  the  nutrition  of  the  hair  itself  requires  a  certain 
supply  of  blood.  The  relatively  insignificant  proportion  of  the  total 
blood  usually  assigned  to  the  skin  of  such  an  animal  as  the  rabbit 
(p.  56)  probably  gives  quite  an  erroneous  idea  of  the  proportion  in 
the  skin  of  a  living  man.  It  must  be  remembered  that  such  determin- 
ations as  have  been  carried  out  have  been  made  on  dead  animals  whose 
skin  under  ordinary  conditions  contains  less  blood  than  during  life. 

Rubner  has  found  that  animals  abundantly  fed  do  not  show  so  much 
change  in  the  production  of  heat  when  the  external  temperature  is 
varied  as  starving  animals,  perhaps  because  the  thicker  coat  of  sub- 
cutaneous fat  so  steadies  the  rate  at  which  heat  is  lost  that  it  becomes 
easy  for  the  vaso-motor  mechanism  alone  to  hold  the  balance  between 
loss  and  production.  In  well-fed  animals  it  is  the  heat-loss  which  is 
chiefly  affected,  and  it  may  be  that  this  has  something  to  do  with  the 
explanation  of  Loewy's  results  on  man  (p.  669). 

Lorrain  Smith  discovered  the  interesting  fact  that  after  removal  of 
the  thyroid  glands  (in  cats),  the  heat-production,  as  measured  by  the 
amount  of  carbon  dioxide  given  off,  is  more  sensitive  to  changes  of 
external  temperature  than  in  the  normal  animal. 

Effect  of  Excessive  Loss  of  Heat-Varnishing  of  the  Skin.  —  It 
must  not  be  imagined  that  the  production  of  heat  can  be  in- 
creased indefinitely  to  meet  an  increased  heat-loss.  The  organism 
can  make  considerable  efforts  to  protect  itself,  but  the  loss  of  heat  may 
easily  become  so  great  that  the  increase  of  metabolism  fails  to  keep 
pace  with  it.  The  internal  temperature  then  falls,  and  if  the  fall  be 
not  checked,  the  animal  dies.  A  mammal,  when  cooled  artificially 
to  the  temperature  of  an  ordinary  room  (15°  to  20°  C),  does  not  recover 
of  itself,  but  may  be  revi\'cd  by  the  employment  of  artificial  respiration 
and  hot  baths,  even  when  the  rectal  temperature  has  sunk  to  5°  to 
10°  C.  If  the  skin  of  a  rabbit  be  varnished,  and  the  air  which  it  is 
the  function  of  the  fur  to  maintain  at  rest  around  it  be  thus  expelled, 
the  animal  dies  of  cold,  unless  the  loss  of  heat  is  artificially  prevented. 
If,  without  varnishing  at  all.  the  greater  portion  of  the  skin  of  a  rabbit 
or  guinea-pig  be  closely  clipped  or  shaved,  similar  phenomena  are 
observed.     Prevented  from  covering  itself  with  straw,  the  animal  dies, 

43 


674  ANIMAL  HEAT 

sometimes  in  twenty-four  hours.  The  radiation  from  the  skin,  as 
measured  by  the  resistance-radiometer  (p.  657).  is  greatly  increased; 
the  animal  shivers  constantly,  and  the  rectal  temperature  falls.  Placed 
in  a  warm  chamber  before  the  temperature  in  the  rectum  has  fallen 
below  25°,  the  animal  recovers  perfectly.  If  the  fall  is  allowed  to  go 
on,  it  dies.  If  it  is  kept  from  the  first  in  the  warm  chamber,  no  fall  of 
temperature  occurs.  When  the  increased  loss  of  heat  is  less  perfectly 
compensated — when,  for  example,  the  animal  is  left  at  the  ordinary 
temperature,  but  supplied  with  sufficient  straw  to  cover  itself,  or 
allowed  to  crouch  among  other  animals — a  curious  phenomenon  may 
sometimes  be  seen.  The  rectal  temperature,  which  has  fallen  sharply 
during  the  operation,  remains  subnormal  (as  much  as  2°  to  3°  below 
the  ordinary  temperature)  for  a  time  (a  week  or  more),  and  then 
gradually  rises  a.^  the  coat  again  begins  to  grow.  The  meaning  of  this 
seems  to  be  that  the  power  of  regulating  the  temperature  by  increasing 
the  metabolism  is  overtasked  by  the  removal  of  the  natural  protective 
covering,  unless  the  escape  of  heat  is  artificially  diminished.  When  the 
loss  of  the  fui'  is  entirely  compensated,  no  fall  of  temperature  occurs; 
when  it  is  not  compensated  at  all,  the. animal  cools  till  it  dies ;  when  it  is 
partially  compensated,  the  increased  metabolism  may  only  suffice  to 
maintain  a  temperature  lower  than  the  normal,  although  constant 
muscular  contractions  (shivering)  are  brought  in  to  supplement  the 
efforts  of  the  regulative  chemical  processes. 

Hitherto  we  have  only  spoken  of  a  reflex  regulation  of  the  heat- 
production  called  into  play  by  external  cold.  It  might  be  sup- 
posed— and,  indeed,  has  often  been  assumed — that  heat  would  lessen 
the  metabolism,  as  cold  increases  it;  and  therf  are  indications  that 
in  the  smaller  animals  this  is  the  case,  although  the  influence  of 
heat  seems  to  be  much  smaller  than  the  influence  of  cold.  But 
neither  experimental  results  nor  general  reasoning  have  as  yet 
shown  that  in  man,  either  in  the  tropics  (Eykman)  or  in  the  north 
temperate  zone  (Loewy),  the  chemical  tone  is  diminished  by  a  rise 
of  external  temperature  much  above  the  mean  of  an  ordinary 
English  summer,  apart  from  the  effect  of  the  muscular  relaxation 
which  heat  induces.  In  a  man,  indeed,  at  rest  in  a  hot  atmosphere, 
the  production  of  carbon  dioxide  and  consumption  of  oxygen  are, 
if  anything,  greater  than  at  the  ordinary  temperature.  The  regu- 
lation of  temperature  in  an  environment  warmer  than  the  normal 
seems,  in  fact,  to  be  brought  about  more  by  an  increase  in  the  loss 
than  a  decrease  in  the  production  of  heat.  Evaporation  from  the 
skin  and  lungs  is  an  automatic  check  upon  overheating  as  important 
as  the  involuntary  increase  of  metabolism  upon  excessive  cooling. 

Nervous  Mechanism  of  Thermotaxis. — While  the  skeletal 
muscles,  and  perhaps  the  glands,  are  at  one  end  of  the  reflex  arc  by 
which  the  impulses  pass  that  regulate  the  temperature  through  the 
metabolism,  we  are  as  yet  ignorant  of  the  precise  paths  by  which 
the  afferent  impulses  travel,  of  the  nerve-centres  to  which  they  go, 
and  even  of  the  end-organs  in  which  they  arise.  There  are  nerves 
in  the  skin  which  minister  to  the  sensation  of  temperature 
(Chap.  XVIIL).     A  change  of  temperature  is  their  '  adequate  '  and 


THERMOTAXIS  675 

sufficient  stimulus;  and  it  is  a  tempting  hypothesis  that  these  are 
the  afferent  nerves  concerned  in  the  reflex  regulation  of  temperature 
— that  impulses  carried  up  by  them  to  some  centre  or  centres  in 
the  brain  or  cord  are  reflected  down  the  motor  nerves  to  control 
the  metabolism  of  the  skeletal  muscles,  and  down  the  vaso-motor 
nerves  to  control  the  loss  of  heat  from  the  skin. 

It  is  more  than  doubtful,  however,  whether  the  whole  chemical  regu- 
lation can  be  attributed  to  such  stimuli.  For  it  has  been  found  that  the 
relation  between  heat-production  and  extent  of  surface  in  animals 
(guinea-pigs)  of  different  size  is  unaltered  when  the  air  temperature  is 
made  so  nearly  the  same  as  that  of  the  skin  that  the  temperature  ner\es 
can  hardly  be  supposed  to  be  excited. 

There  is  some  evidence  that  the  bioplasm — ^the  living  substance — of 
different  animals,  even  when  the  external  conditions  are  the  same,  may 
differ  specifically  in  the  average  intensity  of  metabolism  to  which  it  is 
pitched.  When  exposed  to  a  temperature  about  ecjiial  to  that  of  warm- 
blooded animals,  the  green  lizard  [Lacerta  viridis)  and  the  bull-frog, 
which  live  in  the  temperate  zone,  and  for  which  a  temperature  of 
37°  C.  is  highly  abnormal,  double  their  heat-production,  and  soon  die. 
Tropical  poikilothermal  animals,  such  as  the  alligator,  also  double 
their  heat-production,  but  the  highest  values  reached  are  only  one-half 
that  of  the  lizard  at  25°  C.  Apparently  the  bioplasm  of  the  tropical 
animals  has  adapted  itself  to  a  high  external  temperature,  and  works 
very  economically  even  at  the  highest  temperatures  (Krehl). 

Heat  Centres. — It  is  known  that  certain  injuries  of  the  central 
nervous  system  are  related  to  disturbance  of  the  heat-regulating 
mechanism.  Injury  to  various  portions  of  the  cortex  cerebri  in 
the  dog  and  other  animals,  and  lesions  of  the  pons,  medulla  oblongata 
and  cord  in  man,  may  be  followed  by  increase  of  temperature. 
When  the  spinal  cord  is  cut  below  the  level  of  the  vaso-motor  centre, 
the  increased  loss  of  heat  from  the  skin  due  to  dilatation  of  the 
cutaneous  vessels  masks  any  increase  of  the  heat-production  which 
may  possibly  have  taken  place,  and  the  internal  temperature  falls ; 
but  if  the  loss  of  heat  is  diminished  by  wrapping  the  animal  in 
cotton-wool  the  temperature  may  rise.  From  such  phenomena  it 
has  been  surmised  that  certain  '  centres  '  in  the  brain  have  to  do 
with  the  regulation  of  temperature  by  controUing  the  metabolism 
of  the  tissues;  that  they  cause  increased  metabolism  when  the 
internal  temperature  threatens  to  sink,  diminished  metabolism 
when  it  tends  to  rise.  The  cutting  off,  it  is  said,  of  the  influence 
of  the  '  heat  centres  '  by  section  of  the  paths  leading  from  them 
allows  the  metabolism  of  the  tissues  to  run  riot,  and  the  temjierature 
to  increase.  But  diversity  of  opinion  still  reigns  as  to  the  existence 
or,  if  they  exist,  as  to  the  precise  location  of  the  nervous  centres 
which  preside  over  this  function.  It  is  stated  by  some  workers 
that  animals  deprived  of  the  cerebral  hemispheres,  the  corpora 
striata  and  one  of  the  optic  thalami,  still  maintain  to  a  remarkable 
degree  a  body  temperature  independent  of  their  environment,  but 


676  ANIMAL  HEAl 

that  when  both  optic  thalami  have  been  removed  they  become 
poikilot hernial  (Krehl,  etc).  The  greatest  mass  of  evidence  points, 
however,  to  the  corpora  striata  as  structures  more  intimately  con- 
cerned in  temperature  regulation  than  any  other.  Puncture  of  the 
median  portion  of  the  corpus  striatum  in  the  rabbit  by  a  needle 
thrust  through  a  trephine  hole  in  the  skull  is  followed  in  a  few 
hours  by  a  rise  of  temperature  in  the  rectum  (i°  to  2°),  and  still 
more  in  the  duodenum,  which  is  normally  the  hottest  part  of  the 
body  in  this  animal.  The  heat-production,  the  respiratory  exchange 
and  the  nitrogen  excretion  are  increased.  These  phenomena  may 
last  for  several  days  (Ott,  Richet,  Aronsohn,  and  Sachs),  and  are 
due  to  stimulation  of  the  portions  of  the  brain  in  the  immediate 
neighbourhood  of  the  injury.  Electrical  stimulation  of  this  region 
has  a  similar  effect.  When  the  temperature  has  returned  to 
normal,  a  fresh  puncture  may  again  cause  a  rise. 

As  to  the  manner  in  which  these  centres  are  excited,  there  is 
some  evidence  that,  in  addition  to  any  influence  exerted  on  them 
by  afferent  nerves,  they  are  capable  of  being  directly  affected  by 
the  temperature  conditions  of  the  blood  passing  through  them,  as 
well  as  by  numerous  drugs.  Thus  it  is  stated  by  Barbour  and  Wing 
that  direct  application  of  cold  to  the  region  of  the  corpus  striatum, 
especially  its  caudate  nucleus,  in  rabbits  causes  a  rise  in  the  rectal 
temperature,  associated  with  shivering  and  consequent  increase  of 
heat-production  in  the  contracting  muscles,  and  with  peripheral 
vaso-constriction  and  consequent  diminution  in  the  heat-loss. 
The  application  of  warmth  has  the  opposite  effect :  the  peripheral 
bloodvessels  dilate,  the  animal  becomes  quiet,  and  the  rectal  tem 
perature  falls. 

Some  observers  hold  that  the  chief  seat  of  the  increased  metab- 
olism in  the  puncture  fever  is  the  skeletal  muscles,  others  the  liver. 
The  question  turns  largely  upon  the  success  of  the  puncture  ex- 
periment after  the  previous  administration  of  curara  on  th£  one 
hand,  and  of  strychnine  on  the  other.  For  curara  cuts  out  the 
motor  innervation  of  the  skeletal  muscles,  and  strychnine  convul- 
sions exhaust  the  store  of  hepatic  glycogen.  Certain  investigators 
have  found  that  after  an  adequate  dose  of  curara  no  puncture  fever 
can  be  obtained,  and  they  locate  the  increased  metabolism  asso- 
ciated with  the  fever  in  the  muscles.  Others  maintain  that  even 
after  curara  the  puncture  is  followed  by  fever,  but  is  not  followed 
by  fever  if  strychnine  has  first  been  given.  They  accordingly  con- 
clude that  the  rapid  combustion  of  the  glycogen  (or  the  dextrose 
derived  from  it)  is  the  primary  factor  in  the  increased  metabolism. 
It  may  be  pointed  out,  however,  that  neither  experiment  is  a  crucial 
test.  For  if  strychnine  reduces  the  liver  glycogen,  it  also  reduces 
the  glycogen  of  the  muscles.  And  if  in  the  puncture  fever  the  liver 
glycogen  is  transformed  into  dextrose  more  rapidly  than  usual,  the 


FEVER  677 

dextrose  is  probably  in  great  part  used  up  in  the  muscJes  more 
rapidly  than  usual,  ei33  it  would  appear  in  the  urine.  The  effect 
of  strychnine  on  the  puncture  fever,  then,  is  no  proof  that  the 
muscles  are  not  essentially  concerned  in  it.  On  the  other  hand,  the 
alleged  absence  of  the  fever  after  curara  is  not  sufficient  to  show 
that  the  muscles  are  alone  concerned.  For  curara  causes  a  lowering 
of  the  body-temperature,  which,  if  it  be  not  overcompensated,  ma^' 
mask  the  fever.  The  positive  resirit  of  the  puncture  in  curarized 
animals,  which  some  observers  say  they  have  obtained,  would,  if 
confirmed,  be  important  evidence  that  the  primary  effect  is  not  on 
the  muscles,  or,  at  least,  not  solely  on  them,  but  would  not  prove 
that  it  is  on  the  liver.  That  the  liver  is  concerned,  however,  is  more 
directly  indicated  by  the  fact  that  during  the  puncture  fever  the 
liver  continues  to  be  what  it  is  under  normal  conditions,  the  warmest 
organ  in  the  body,  warmer  than  the  blood  in  the  root  of  the  aorta 
by  about  1°  C.  The  most  probable  conclusion  is  that  the  increased 
production  of  heat  in  this  form  of  experimental  fever  is  due  to  an 
increased  metabolism  of  carbo-hydrate  (glycogen)  both  in  the  liver 
and  in  the  muscles. 

Temperature  Regulation  in  Hibernating  Animals. — The  behaviour 
of  hibernating  mammals,  such  as  the  marmot,  dormouse,  hedgehog, 
and  bat,  is  of  interest  in  connection  with  the  temperature  regulation. 
In  the  active  waking  state  these  animals  are  homoiothermal,  but  in 
profound  winter  sleep  they  are  poikilothermal,  the  body- tempera- 
ture rising  and  falling  wath  that  of  the  air.  The  rectal  temperature 
may  be  as  low  as  2°  C  There  is  an  intermediate  state  in  which  the 
animal  is  partially  awake,  though  inactive,  and  its  temperature  is 
much  below  the  normal,  but  considerably  above  that  of  its  environ- 
ment. In  this  condition  it  has  an  imperfect  thermotaxis,  something 
like  that  of  an  ordinary  mammal  (including  the  human  infant)  in 
the  period  of  immaturity,  immediately  after  birth.  When  the 
hibernating  mammal  awakes  the  rise  of  temperature  is  enormous 
and  abrupt.  The  temperature  of  a  dormouse  rose  in  an  hour  from 
135°  C.  to  357°  C,  and  that  of  a  bat  in  fifteen  minutes  from  17°  C 
to34°C.  (Pombrey). 

Fevers. — Fever  is  a  pathological  process  generally  caused  by  the 
poisonous  products  of  bacteria,  and  characterized  by  a  rise  of 
temperature  above  the  limit  of  the  daily  variation  (p.  686).  It  is 
further  associated  with  an  increase  in  the  rate  of  the  heart  and  the 
respiratory  movements,  and  a  diminution  in  the  alkalies  and  carbon 
dioxide  of  the  blood.  The  total  excretion  of  nitrogen  is  increased, 
at  least  in  proportion  to  the  amount  of  protein  ingested,  intlicating 
an  increase  in  the  consumption  of  tissue-protein.  The  distribution 
of  the  nitrogen  among  the  urinary  constituents  is  altered.  The 
ammonia  (in  the  form  of  ammonium  salts  of  organic  acids),  the 
uric  acid,  and  to  a  smaller  extent  the  kreatinin  (Leathes).  are  in- 


678  ANIMAL  HEAT 

creased,  while  the  urea  is  relatively  decreased,  even  when  its  abso- 
lute amount  is  greater  than  normal.  Kreatin,  which  is  not  normally 
present  in  urine,  unless  the  food  contains  it,  may  also  appear  in 
fever  (Shaffer).  It  has  been  suggested  that  the  proximate  cause  of 
fever  is  the  action  of  bacterial  poisons  or  of  other  substances  on  the 
'  heat  centres,'  and  that  antip3Tetics,  or  drugs  which  reduce  the 
temperature  in  fever,  do  so  by  restoring  the  centres  to  their  normal 
state,  by  preventing  the  development  of  the  poisons,  aiding  their 
elimination,  or  antagonizing  their  action.  In  favour  of  this  view, 
it  has  been  stated  that  when  the  basal  ganglia  are  cut  off,  b}-  section 
of  the  pons,  from  their  lower  nervous  connections,  fever  is  no  longer 
produced  by  injection  of  cultures  of  bacteria  which  readily  cause  it 
in  an  intact  animal,  while  antipyrin  has  no  influence  upon 
the  temperature  (Sawadowski).  And  while  it  is  almost  certain 
that  some  pyrogenic  or  fever-producing  agents — cocaine,  e.g. — act 
indirectly,  through  the  brain  or  cord,  it  is  quite  possible  that  others 
affect  directly  the  activity  of  the  tissues  in  general,  just  as  some 
antipyretics  or  fever-reducing  agents,  such  as  quinine,  act  imme- 
diately upon  the  heat-forming  tissues,  so  as  to  diminish  their 
metabolism,  while  others,  like  antipyrin,  affect  them  through  the 
nervous  system.  Quinine  has  no  influence  upon  '  puncture  '  fever 
in  rabbits.  A  still  more  important  action  of  antip}Tin,  and  the 
group  of  antipyretics  to  which  it  belongs,  is  the  increase  in  the  heat- 
loss  which  they  bring  about  by  the  dilatation  of  the  bloodvessels 
of  the  skin.  This  effect  is  also  produced  through  the  nervous  system. 
Fever  is  a  condition  so  interesting  from  a  physiological  point  of 
view,  and  of  such  importance  in  practical  medicine,  that  it  will  be 
well  to  consider  a  little  more  closely  the  possible  ways  in  which  a 
rise  of  temperature  may  occur.  It  must  not  be  forgotten  that  the 
febrile  increase  of  temperature  is  always  accompanied  by  other 
departures  from  the  normal,  and  that  all  the  fundamental  febrile 
changes  may  even,  in  certain  cases,  be  present  without  elevation, 
and  even  with  diminution  of  temperature.  But  here  we  have  only 
to  do  with  the  disturbance  of  the  normal  equilibrium  between  the 
loss  and  the  production  of  heat;  and  it  is  evident  that  any  of  the 
five  conditions  illustrated  in  the  diagram  (Fig.  215)  may  give  rise 
to  an  increase  of  temperature.  It  is  not  necessary  to  discuss 
whether  cases  of  fever  can  actually  be  found  to  illustrate  every  one 
of  these  possibihties.  It  is  probable  that  not  infrequently  dimin- 
ished loss  and  increased  production  may  be  both  involved ;  and  it 
ought  to  be  remembered  that  the  healthy  standard  with  which  the 
heat-production  of  a  fever  patient  should  be  compared  is  not  that 
of  a  man  doing  hard  work  on  a  full  diet,  but  that  of  a  healthy  person 
in  bed,  and  on  the  meagre  fare  of  the  sick-room.  When  this  is  kept 
in  view,  the  comparatively  low  heat-production  and  respiratory 
exchange  which  have  sometimes  been  found  in  fever  cease  to  excite 


FEVER 


679 


surprise.  But  in  any  case,  no  mere  change  in  the  absolute  quantities 
of  heat  formed  and  lost  is  sufficient  to  explain  the  febrile  rise  of 
temperature;  there  must  be  a  change  in  the  relative  proportion. 
That  an  increase  in  heat-production  is  not  of  itself  enough  to  produce 
fever  is  proved  by  the  fact  that  severe  muscular  work,  which  in- 
creases the  metabolism  more  than  high  fever,  only  causes  in  a 
healthy  man  a  rise  of  about  i*"  C.  in  the  rectal  temperature.  When 
the  work  is  over,  the  temperature  comes  rapidly  back  to  normal. 
The  essence  of  the  change  in  fever  is  a  derangement  of  the  mechanism 
by  whicii  in  the  healthy  body  excess  or  defect  of  average  metab- 
olism, or  of  average  heat- 
loss,  is  at  once  compensated 
and  the  equilibrium  of  tem- 
perature maintained. 

This  derangement  only  lasts 
as  long  as  the  temperature 
is  rising.  When  it  becomes 
stationary  at  its  maximum 
we  have  again  adjustment, 
again  equality  of  production 
and  escape  of  heat;  but  the 
adjustment  is  now  pitched 
for  a  higher  scale  of  tempera- 
ture. A  rough  analogy,  so 
far  as  one  part  of  the  process 
is  concerned,  may  be  found 
in  the  behaviour  of  the 
ordinary  gas-regulator  of  a 
water-bath.  It  can  be  '  set ' 
for  any  temperature.  That 
temperature,  once  reached, 
remains  constant  within  nar- 
row limits  of  oscillation;  but 
the  regulator  can  be  equally 
well  adjusted  for  a  higher  or 
a  lower  temperature.  It  is, 
however,  important  to  note  that  the  equilibrium  is  more  unstable 
in  fever  than  in  health,  so  that  changes  of  external  temperature  more 
easily  depress  or  increase  the  temperature  of  a  fever  patient  than  of 
a  healthy  man. 

Rosenthal  has  concluded  from  calori metric  observations  that,  in 
the  first  stage  of  fever,  while  the  tem])orature  is  rising,  there  is 
always  increased  retention  of  heat.  Maragliano  actually  found 
evidence,  by  means  of  the  plethysmograph,  that  the  cutaneous 
vessels  are  at  this  stage  constricted,  and  that  the  constriction  may 
even  precede  the  rise  of  temperature.     The  blood-flow  in  the  feet 


I<"ig.  215. — Diagram  to  show  tiie  Possible 
Relations  between  Heat- Production  and 
Heat-Loss  in  Fever. 


68o  4J<^IMAL  HEAT 

in  cases  of  typhoid  fever  investigated  by  the  calorimetric  method 
(p.  122)  was  not  found  to  exceed  the  normal  flow,  and  was  usually 
decidedly  below  the  normal.  Hyperexcitability  of  the  vaso-con- 
strictor  mechanism  of  the  peripheral  parts,  especially  of  the  skin, 
was  present.  All  these  observations  lend  support  to  the  famous 
'  retention  '  theory  of  Traube.  It  has  been  suggested  that  the 
significance  of  the  increased  action  of  the  cutaneous  vaso-constrictor 
mechanism  in  typhoid  fever  is  that  the  peripheral  vaso-constriction 
is  a  compensatory  arrangement  which  secures  for  the  organs  mainly 
suffering  from  the  infective  process  an  increased  flow  of  blood  to 
combat  the  infection.  On  this  hypothesis  the  rise  of  temperature 
in  so  far  as  it  depends  upon  diminished  loss  of  heat  is  a  secondary 
phenomenon  inevitably  following  the  redistribution  of  the  blood, 
and  unavoidable  except  by  a  corresponding  diminution  in  the  total 
metabolism.  In  the  great  majority  of  cases  the  production  of  heat 
is  also  increased,  on  the  average  by  20  to  30  per  cent,  of  the  normal 
production  of  a  resting  man.  The  increase  may  be  much  greater 
during  the  chill  which  ushers  in  so  many  infections  on,  account  of 
the  muscular  contractions  in  shivering.  During  the  period  of  rising 
temperature  the  production  of  heat  is  not  necessarily  increased. 
At  the  height  of  the  fever  there  is  often,  though  apparently  not 
always,  an  increase  in  the  heat-production.  After  the  crisis,  while 
the  fever  is  subsiding,  the  rate  at  which  heat  is  lost  rises  sharply. 
As  to  the  explanation  of  the  increase  of  metabolism  in  fever, 
and  especially  of  the  increased  metabolism  of  tissue-protein, 
various  views  have  been  held.  Some  have  gone  so  far  as  to  say 
that  the  increase  is  merely  the  consequence,  not  the  cause,  of 
the  rise  of  temperature.  But  the  rebutting  evidence  which  has 
been  brought  against  this  view  is  strong  and,  indeed,  overwhelming. 
It  is  perfectly  true  that,  when  the  temperature  of  the  body  is 
artificially  raised  by  preventing  the  free  loss  of  heat  for  a  sufficient 
time  (so-called  physiological  fever),  the  destruction  of  protein  is 
augmented.  A  fasting  dog  whose  temperature  was  increased  to 
40°  or  41°  C  for  twelve  hours  eliminated  37  per  cent,  more  nitrogen 
than  when  the  body-temperature  was  normal.  But  this  increase 
in  th^  protein  metabolism  could  be  entirely  prevented  by  giving 
the  animal  a  sufficient  amount  of  carbo-hydrate.  Similar  results 
have  been  obtained  in  man.  The  carbon  dioxide  excretion  and 
oxygen  absorption  are,  of  course,  also  markedly  increased.  But  the 
increase  in  the  nitrogen  excretion  is  often  Tuuch  greater  in  fever  than 
any  increase  which  can  be  brought  about  by  artificially  raising  the 
temperature  of  a  healthy  individual  by  means  of  hot  baths.  A 
typhoid  patient  was  found  to  lose  io-8  grammes  of  nitrogen  a  day 
(co  responding  to  318  grammes  of  mus'le)  during  eight  days  of 
fover  (F.  Miiller).  A  portion  of  the  loss  of  nitrogen  on  the  routine 
fever  regimen  may  be  due  to  the  fact  that  the  ordinary  typhoid 


FEVER  68i 

patient  is  really  on  a  semi-starvation  diet,  the  heat-equivalent  of 
which  is  not  much  more  than  half  his  heat-production.  Yet  it 
has  not  been  found  possible  to  completely  prevent  the  loss  of 
nitrogen  by  putting  the  fever  patient  on  a  diet  rich  in  protein,  or 
on  a  diet  containing  a  moderate  amount  of  protein  with  a  large 
quantity  of  fat  and  carbo-h3'drate,  even  when  the  total  heat-value 
of  the  diet  is  much  in  excess  of  the  32  or  33  calories  per  kilo  of  body- 
weight  which  corresponds  to  the  heat-production  of  a  resting  man. 
Another  suggestive  fact  is  that  the  excessive  excretion  of  nitrogen 
does  not  run  parallel  with  the  rise  of  temperature  in  fever,  but  is 
often  most  marked  after  the  crisis.  During  the  stage  of  defer- 
vescence an  enormous  amount  of  urea  is  sometimes  given  off.  In  a 
case  of  typhus,  in  the  mixed  urine  of  the  third  and  fourth  days  after 
the  crisis,  no  less  than  160  grammes  of  urea  was  found  (NaunjTi),  or 
nearly  three  times  the  normal  amount  for  a  man  on  full  diet.  Again, 
when  fever  is  caused  by  the  injection  of  bacteria  or  their  products, 
the  increase  in  the  carbon  dioxide  eliminated  and  oxygen  consumed 
occurs  even  when  the  temperature  is  prevented  from  rising  by  cold 
baths.  It  seems  perfectly  clear,  then,  that  the  increase  oif  metab- 
olism is,  in  many  cases  at  least,  a  primary  phenomenon  of  fever. 
Its  course  and  incidence,  falling  as  it  does  so  largely  upon  the 
proteins,  the  steady  loss  of  tissue  nitrogen,  and  the  inability  of  the 
tissues  to  recoup  their  losses  from  the  protein  of  the  food  or  to 
shield  their  own  protein  by  burning  more  carbo-hydrate  or  fat,  all 
suggest  that  the  cells  are  poisoned  by  toxic  products  of  the  infective 
process.  The  poisoned  bioplasm  falls  an  easy  prey  to  the  hydro- 
lysing  and  oxidizing  agents  always  present  in  the  tissues.  It  breaks 
down  more  rapidly  and  builds  itself  up  more  slowly  than  normal 
bioplasm.  This  increased,  and  to  some  extent  perverted,  metab- 
olism, far  from  being  occasioned  by  the  febrile  temperature,  is  quite 
probably  the  cause  of  the  thermo-regulative  upset  which  we  call  fever. 
For  Mandel  has  shown — (i)  that  one  of  the  purin  bases  (xanthin) 
causes  fever  in  monkeys;  (2)  that  the  purin  bases  in  the  urine  are 
increased  both  in  infective  fevers  and  the  so-called  aseptic  or  surgical 
fever — that  is,  in  cases  where  the  temperature  rises  after  such  injuries 
as  extensive  crushing  of  tissues  without  infection.  There  is  a  con- 
stant relation  between  the  height  of  the  fever  and  the  quantity  of 
purin  bases  excreted.  The  source  of  the  purin  bases  in  aseptic  fever 
is  presumably  the  autolysis  of  the  injured  tissue,  from  which  they 
pass  into  the  blood  without  being  oxidized  to  uric  acid.  The  xanthin 
fever  can  be  prevented  by  salicylates,  though  not  by  antipyrin. 

It  has  been  very  generally  admitted  that  the  chief  seat  of  excessive 
metabolism  in  fever  is  the  muscles;  but  U.  Mosso  has  stated  that 
cocaine  fever — the  marked  rise  of  temperature  produced  by  injec- 
tion of  cocaine — can  be  obtained  in  animals  paralyzed  by  curara. 
This,  even  if  true,  would  not  support  the  conclusion  that  a  '  nervous 


682  ANIMAL  HEAT 

fever  ' — that  is  to  say,  a  fever  due  solely  to  increase*d  metabolism 
in  the  nervous  system — exists;  for  in  a  curarized  animal  a  large 
amount  of  '  active  '  tissue  (glands,  heart,  smooth  muscle)  still 
remains  in  physiological  connection  with  the  brain  and  cord.  But, 
as  a  matter  of  fact,  in  an  animal  under  a  dose  of  curara  sufficient 
to  completely  paralyze  the  skeletal  muscle  cocaine  causes  no  appre- 
ciable rise  of  rectal  temperature ;  and  this  is  strongly  in  favour  of 
the  view  that  the  fever  produced  in  the  non-curarized  animal  is 
connected  with  excessive  muscular  metabolism. 

Significance  of  the  Increased  Temperature  in  Fever. — It  remains 
to  ask  whether  the  rise  of  temperature  is  anything  more  than  a 
superficial  and,  so  to  speak,  an  accidental  circumstance.  The 
question  has  already  been  raised  in  discussing  the  changes  in  the 
circulation  in  fever  (p.  680).  The  orthodox  view  for  many  ages 
has  undoubtedly  been  that  the  increase  of  temperature  is  in  itself 
a  serious  part  of  the  pathological  process,  a  symptom  to  be  fought 
with  and,  if  possible,  removed.  And,  indeed,  it  is  not  denied  by 
anyone  that  the  excessive  rise  of  temperature  seen  in  some  cases  of 
febrile  disease  (to  43°  C,  or  even  to  45°)  is,  apart  from  all  other 
changes,  a  most  imminent  danger  to  life,  unless,  as  is  sometimes  the 
case  (in  influenza,  eg.,  where  a  temperature  of  44°  has  been  observed), 
the  high  temperature  lasts  only  a  short  time.  Experimental  heat 
paralysis,  a  condition  in  which  all  voluntary  and  reflex  movements 
are  abolished,  is  produced  in  frogs  by  raising  the  internal  tempera- 
ture to  about  34°  C.  On  cooling,  the  animal  recovers.  A  similar 
condition  can  be  induced  in  mammals,  but,  of  course,  at  a  higher 
temperature.  The  central  nervous  system  succumbs  before  the 
peripheral  structures.  The  superior  cervical  ganglion  in  the  cat  01 
rabbit  loses  the  power  of  transmitting  nerve  impulses  at  50°  C. 
But  some  evidence  has  been  brought  forward,  mostly  from  the  field 
of  bacteriology,  to  support  the  idea  that  in  infective  processes  the 
rise  of  temperature  is  of  the  nature  of  a  protective  mechanism,  thai 
the  fever  is,  indeed,  a  consuming  fire,  but  a  fire  that  wastes  the  body, 
to  destroy  the  bacteria.  The  streptococcus  of  erysipelas,  for  ex- 
ample, does  not  develop  at  39°  to  40°  C.,  and  is  killed  at  39*5°  to 
41°  C,  and  erysipelas  infections  in  rabbits  are  less  virulent  if  the 
bod  y-temperature  be  artificially  raised.  Anthrax  bacilli,  kept  at 
42°  to  43°  C.  for  some  time,  are  attenuated,  and  when  injected  into 
animals  confer  immunity  to  the  disease.  Heated  for  several  days 
to  41°  to  42°  C,  pneumococci  render  rabbits  immune  to  pneumonia, 
and  in  rabbits  in  which  '  puncture  '  fever  has  been  induced  pneumo- 
coccus  infections  run  a  milder  course.  These  bacteriological  results 
are  supported  to  a  certain  extent  by  clinical  experience.  For  it  has 
been  observed  that  a  cholera  patient  with  distinct  fever  has  a 
better  chance  of  recovery  than  a  case  which  shows  no  fever.  But 
too  much  weight  ought  not  to  be  given  to  isolated  facts  of  this  sort, 


TEMPERATURE  TOPOGRAPHY  683 

and  adverse  evidence  can  be  produced  both  from  the  laboratory 
and  the  hospital.  For  although  hens  are  immune  to  anthrax  under 
ordinary  conditions,  but  can  be  infected  by  inoculation  when 
artificially  cooled,  frogs,  equally  immune  at  the  temjxirature  of  the 
air,  become  susceptible  when  artificially  heated.  And  it  is  impos- 
sible to  deny  that  the  use  of  cold  baths  in  typhoid  fever  is  sometimes 
of  remarkable  benefit.  This  benefit,  however,  while  very  unhkely 
to  be  connected  with  any  directly  unfavourable  action  of  the  reduced 
body-temperature  on  the  growth  of  the  bacilli,  may  perhaps  be  due, 
in  some  part  at  least,  to  an  increase  in  the  cutaneous  vaso-con- 
striction  which  ht-lps  to  send  through  the  infected  intestine  a  more 
copious  stream  of  blood. 

Section  IV. — Distribution  of  Heat — Temperature 
Topography. 

The  great  foci  of  hoat-formotion — the  muscles  and  glands — would, 
if  heat  were  not  constantly  leaving  them,  in  a  short  time  become 
much  warmer  than  the  rest  of  the  body;  while  structures  like  the 
bones,  skin,  and  adipose  tissue,  in  which  chemical  change  and  heat- 
production  are  slow,  would  soon  cool  down  to  a  temperature  not 
much  exceeding  that  of  the  air.  The  circulation  of  the  blood 
insures  that  heat  produced  in  any  organ  shall  be  carried  away  and 
sp.^edily  distributed  over  the  whole  body;  while  direct  conduction 
also  plays  a  considerable  part  in  maintaining  an  approximately 
uniform  temperature.  The  uniformity,  however,  is  only  approxi- 
mate. The  temperature  of  the  liver  is  several  degrees  higher  than 
that  of  the  skin,  and  the  temperature  of  the  brain  several  degrees 
higher  than  that  of  the  cornea.  The  blood  of  the  superficial  veins 
is  colder  than  that  of  the  corresponding  arteries. 

The  crural  vein,  for  example,  carries  colder  blood  than  the  crural 
artery,  and  the  external  jugular  than  the  carotid.  The  heat  produced 
in  the  deeper  parts  of  the  regions  which  they  drain  is  more  than  counter- 
balanced by  the  heat  lost  in  the  more  superficial  parts.  When  loss  of 
heat  from  the  surface  is  sufficiently  diminished  by  an  artificial  covering, 
or  prevented  by  the  protected  situation  of  any  organ  with  an  active 
metabolism,  the  venous  blood  leaving  it  is  warmer  than  the  arterial 
blood  coming  to  it.  The  temperature  of  the  blood  passing  from  the 
levator  labii  superioris  muscle  of  the  horse  during  mastication  may  be 
sensibly  higher  than  that  of  the  blood  which  feeds  it;  the  blood  in  the 
vena  profunda  fcmoris,  and  in  the  crural  vein  of  a  dog  with  the  leg 
wrapped  in  cotton-wool,  is  warmer  by  0*1°  to  0-3°  than  of  the  crural 
artery.  The  difference  is  due  to  the  heat  produced  in  the  muscles,  and  it 
ought  to  be  of  this  order  of  magnitude.  The  quantity  of  blood  in  a 
7-kilo  dog  is  about  \  kilo ;  \  of  this,  or  ji  kilo,  is  in  the  skeletal  muscles, 
and  the  average  circulation-time  through  them  may  be  taken  as  ten 
seconds.  Six  times  in  the  minute,  or  360  times  in  the  hour,  J  kilo  of 
blood  passes  through  the  muscles,  and  is  heated  on  the  average  by  0'Z°. 

This  represents  a  heat-production  of  about     o~  x  — ,  or  9  calories  f)er 


684  ANIMAL  HEAT 

hour.  Now,  the  total  heat-production  of  a  7-kilo  dog  is  about 
19  calories  per  hour,  of  which  somewhat  less  than  one-half  is  formed 
in  the  skeletal  muscles. 

The  blood  of  the  inferior  vena  cava  at  the  level  of  the  kidneys  may 
be  o*i°  colder  than  that  of  the  abdominal  aorta,  but  is  warmer  than 
the  blood  of  the  superior  cava.  The  right  heart,  therefore,  receives 
two  streams  of  blood  fit  different  temperatures,  which  mingle  in  its 
cavities.  A  controversy  was  long  carried  on  as  to  the  relative  tem- 
perature of  the  blood  of  the  two  sides  of  the  heart ;  but  the  researches 
of  Ileidenhain  and  Korner  have  shown  that  a  thermometer  passed  into 
the  right  ventricle  through  the  jugular  vein  stands,  as  a  rule,  slightly 
higher  than  a  thermometer  introduced  through  the  carotid  into  the 
left  ventricle.  The  method  gives  not  so  much  the  temperature  of  the 
blood  in  the  two  cavities  as  that  of  their  walls.  The  thin-walled  right 
ventricle  is  heated  by  conduction  from  the  warm  liver,  from  which  it  is 
only  separated  by  the  diaphragm,  while  the  left  ventricle  loses  heat 
to  tlie  cooler  lungs.  The  difference  of  temperature  is  not  caused  by 
cooling  of  the  blood  in  its  passage  through  the  pulmonary  capillaries, 
for  even  when  respiration  is  suspended,  a  difference  of  temperature 
between  the  two  sides  of  the  heart  is  found.  Under  ordinary  circum- 
stances, the  inspired  air  is  already  heated  almost  to  body-temperature 
before  it  reaches  the  alveoli.  But,  while  this  is  the  case,  a  fall  of  less 
than  j^°  in  the  temperature  of  the  blood  passing  through  the  lungs 
would  account  for  all  the  heat  lost  by  the  expired  air.  If  half  of  the 
loss  took  place  in  the  upper  air-passages,  less  than  ;}^^°  would  be  suffi- 
cient. A  slight  difference  of  temperature  in  the  blood  of  the  two  ven- 
tricles might  be  caused,  even  in  the  absence  of  respiration,  by  the  heat 
developed  in  the  cardiac  muscle  itself  during  contraction,  a  large  pro- 
portion of  which  must  be  conveyed  by  the  coronary  veins  into  the  right 
h«arti 

The  surface  temperature  varies  between  rather  wide  limits  with  the 
temperature  of  the  environment.  The  temperature  of  cavities  like 
the  rectimi,  vagina,  and  mouth,  and  of  secretions  like  the  urine,  approxi- 
mates to  that  of  the  blood  in  the  great  vessels  or  the  heart,  and  under- 
goes only  slight  changes.  An  increase  in  the  velocity  of  the  blood  causes 
the  internal  and  surface  temperatures  to  come  nearer  to  each  other, 
the  former  falling  and  the  latter  rising.  When  the  loss  of  heat  from 
a  portion  of  the  surface  is  prevented,  the  temperature  of  this  portion 
approaches  the  internal  temperatupe.  For  this  reason  a  thermometer 
placed  in  the  axilla  approximately  measures  the  internal  temperature, 
and  not  that  of  the  skin;  and  a  thermometer  in  the  groin  of  a  rabbit, 
and  completely  covered  by  the  flexed  thigh,  may  stand  as  high  as,  or, 
it  is  said,  even  liigher  than,  a  thermometer  in  the  rectum  (Hale  White). 
The  temperature  in  the  mouth  is  not  a  very  reliable  index  of  the  deep 
temperature  of  the  body,  especially  in  cold  weather  or  after  exercise, 
as  it  is  apt  to  be  influenced  by  the  inspired  air.  The  mouth  must,  of 
course,  be  kept  closed  during  the  measurement.  On  the  average  its 
temperature  is  about  the  same  as  that  of  the  axilla,  and  0*4°  C.  below 
that  of  the  rectum*  The  rectal  temperature  is  0*2°  or  0*3°  above  that 
of  the  urine.  In  point  of  accuracy  rectal  observations  are  the  best,  and 
next  to  them  determinations  of  the  temperature  of  the  stream  of  urine. 
The  latter  method,  although  subject  to  obvious  limitations,  is  rapid  and 
free  from  the  danger  of  conveying  infection  to  the  person  (Pembrey). 

The  surface  temperature  is  a  rough  index  of  the  rate  of  heat-loss; 
the  internal  temperature,  of  the  rate  of  heat-production.  A  normal 
skin  temperature  and  a  rising  rectal  temperature  would  probaldy  in- 
dicate increased  production  of  heat ;  an  increased   rectal  temperature. 


TEMPERATURE  TOPOGRAPHY  685 

in  conjunction  with  a  diminished  surface  temperature,  as  in  the  cold 
stage  of  ague,  might  be  due  either  to  diminished  heat-loss  while  the 
heat-production  remained  normal,  or  to  diminished  heat-loss  plus 
increased  heat-production. 

Tlie  following  tables  illustrate  the  differences  of  temperature  found 
in  the  body.  It  should  be  remembered  that  the  numbers  are  not 
strictly  comparable  with  each  other;- the  temperature  of  the  mammals 
in  which  direct  observations  have  been  made  on  the  blood  is  not 
exactly  the  same  as  that  of  man,  the  temjicrature  of  the  dog,  for 
example,  being  a  little  (about  1°  C.)  higher.  Then  in  the  same  animal 
there  is  no  very  constant  ratio  between  the  temperature  of  the  blood 
in  two  vessels  or  of  the  skin  at  two  points.  Even  in  tiie  same  vessel 
the  temperature  may  vary  with  many  circumstances,  such  as  the 
velocity  of  the  stream,  and  the  state  of  activity  of  the  organ  from  which 
it  comes.  Apart  from  physiological  variations,  experimental  fallacies 
sometimes  cause  a  want  of  constancy,  especially  in  measurements  of 
blood  temperature.  The  insertion  of  a  mercurial  thermometer  into  a 
vessel  is  very  likely  to  obstruct  the  passage  of  th«  blood;  and  if  the 
blood  lingers  in  a  warm  organ,  it  will  be  heated  beyond  the  normal. 
In  man  the  blood-temperature  in  th©  arteries  at  the  wrist  has  been 
estimated  indirectly  by  the  calorimetric  method  of  measuring  the 
blood-flow  in  the  hand  (p.  122),  probably  with  greater  accuracy  than 
would  be  attainable  by  the  direct  insertion  of  a  tliermometer,  were 
this  permissible.  The  temperature  of  the  calorimeter  is  determined  at 
which  it  neither  imparts  heat  to  the  blood  nor  gains  heat  from  the  blood. 
On  the  assumption  that  the  heat-production  of  the  resting  hand  is 
negligible  for  tliis  purpose,*  the  temperature  so  fixed  will  be  that  at 
which  the  blood  enters  the  hand— i.e.,  the  temperature  of  the  arterial 
blood  at  the  wrist. 

Blood.     {Dog.) 

Right  heart         .         .         _         .     38-8°  C. 

Left         ,, 38-6 

Aorta  ------     38-7 

Superior  vena  cava       -         -         -     36-8 

Inferior  ,,  -         -         -     381 

Crural  vein  -         -         _         .         _     37-2! 
artery        -         .         -         -     38-0 

Profunda  femoris  vein  -         -     38-2 

Portal  vein  -         -         -         -  38-39     )  Varies  with  activity 

Hepatic  vein         -         -         .       38-4-39-7  J  of  digestive  organs. 

Arterial  blood  at  wrist  in  man     -        0-5  below  rectal  temperature. 

*  Since,  of  course,  some  heat  is  produced  in  the  hand  even  at  rest,  although 
doubtless  less  per  unit  of  weight  than  m  the  resting  body  as  a  whole,  the 
arterial  blood  temperature  as  thus  determined  must  be  somewliat  too  high. 
No  error  is  caused  by  this  in  tlic  calculation  of  the  blood-flow  in  the  hand 
(p.  122) ;  for  while  the  factor  T — T'  in  the  denominator  is  somewhat  too  great, 
thv  corresponding  quantity  of  heat  produced  in  the  hand  is  included  in  H  in 
the  numerator. 

f  The  following  numbers  were  obtained  (in  an  anaesthetized  dog  whose 
rectal  temperature  had  fallen  2°  C.)  for  the  temperature  of  the  ivalls  of  the 
orural  artery  and  vein,  as  measured  by  an  electrical  re.sistance  thermometer. 

Leg  of  dog  lightly  wrapped  in  wool. 

Crural  artery  .         .         -         .         .  34-95 

vein     ---.-_  3476    Rcclum,  36*2 
Leg  more  carefully  wrapped  up.  [Air,  io'3 

Crural  artery  -----  34- 70 

vein 3482, 


636  ANIMAL  HEAT 

Tissues. 
Brain  ------     40°  C 

Liver    ------     40'6-40'9 

Subcutaneous  tissue  2-1  lower  than 
that  of  subjacent  muscles  (man). 
Anterior  chamber  of  eye        -         -     3i*9\,     \  uj\ 
Vitreous  humour  -         -         -     36-1  j^'^^'^^^^'- 

Cavities.  [Man.) 

Axilla         ....  36-3-37-5°  C.  (97-3-99-5°  F-)« 

Rectum      .         _         -         -  36-37-8 

Mouth        ....  37-25 

Vagina        ....  37-5-38 

Uterus        ....  37-7-38-3 

External  auditory  meatus  -  37*3-37'8 
Bladder  (temperature  of  the 

escaping  urine)        -         -  36-0-37-5 

Respiratory  Passages.  {Horse.) 

Air  TMiddle  of  nasal  cavity    -  -     23-4°  C. 

temperature,  -|        ,,  trachea  -         -  .     32-4  in  inspiration. 

4-5°  C.        i       ,,  It         -         -  -     34*4  in  expiration. 

Natural  Surfaces, 

Cheek  (boy,  immediately  after  running)         -  36-25° 

(Anterior  surface  of  forearm  ...  33-5-34-4 

Posterior        ,,  ,,  -         -         -         -  34-0 

Skin  over  biceps  ....         -  3^-0 

temperature,        ,,       ,,      head  of  tibia       -         -         -         -  3i'9 

17-5°  ,,      immediately  below  xiphoid  cartilage  -  34-7 

\^     ,,      over  sternum       .....  33-2 

On  hair  (boy)        -...._  30-0 

Under  hair  over  sagittal  suture   (boy)         -  33'7-34*o 

Shaved  skin  of  neck  (rabbit)       ...  36-5 
On  hair         ,,         ,,           ,,             -         -         -31  "S 

,,       between  eyes        ,,  _        _        .  30-7 

Artificial  Surfaces. 

Room  Surface  of  trousers  over  thigh      -         -         .  2 3- 7-2 8- 7"^ 

temperature,]  "  coat  over  arm    -         -         -         -  26-8 

\.„  .0  ,,  waistcoat     -----  26-0 

Normal  Variations  in  the  Temperature. — The  internal  tempera- 
ture, as  has  been  already  said,  is  not  strictly  constant.  It  varies 
with  the  time  of  day;  with  the  taking  of  food;  with  age;  to  some 
extent  with  violent  changes  in  the  external  temperature,  such  as 
those  produced  by  hot  or  cold  baths;  and  possibly  with  sex.  On 
the  average  the  range  of  variation  in  the  temperature  of  the  rectum 
or  urine  of  a  healthy  man  is  from  36*0°  C.  (96-8°  F.)  to  37*8°  C. 
(100-0°  F.). 

In  the  monkey  a  very  distinct  and  constant  diurnal  variation  has 
been  observed,  and  the  range  is  much  wider  than  in  man  (as  much 
as  5*4°  F.),  the  maximum  falling  between  6  and  8  p.m.  and  the 
minimum  between  2  and  4  a.m.  (Simpson). 


TEMPERA  T  UJiE    1  OPOG  RA  RH  V 


687 


'Jhe  daily  curve  of  temperature  shows  a  minimum  in  the  early 
morning,  between  two  and  six  o'clock  (36-3°  C),  and  a  maximum 
in  the  evening,  between  five  and  eight  o'clock  (37*5°  C)  (Fig.  216). 
The  daily  range  in  health  may  be  taken  as  a  little  over  1°  C,  or 
about  2°  F.  In  fever  it  is  generally  greater,  but  the  maximum  and 
minimum  fall  at  the  same  periods;  and  it  is  of  scientific,  and  also 
of  practical,  interest  that  the  early  morning,  when  the  temperature 
and  pulse-rate  are  at  their  minimum,  is  often  the  time  at  which  the 
flagging  powers  of  the  sick  give  way.  From  two  to  six  o'clock  in 
the  morning  the  daily  tide 
of  life  may  be  said  to  reach 
low-water  mark  Even  in 
a  fasting  man  the  diurnal 
temperature  curve  runs  its 
course,  but  the  variations 
are  not  so  great.  The  ta- 
king of  food  of  itself  causes 
an  increase  of  temperature, 
although  in  a  healthy  man 
this  rarely  amounts  to  more 
than  half  a  degree.  The  rise 
of  temperature  is  certainly 
due  in  part  to  the  increased 
work  of  the  alimentary 
canal,  but  it  is  in  the  main 
connected  with  the  increase 
of  metabolic  activity  which  the  entrance  of  the  products  of  digestion 
into  the  blood  brings  about.  The  heat-production  is  especially 
increased  by  proteins. 

A  dog  weighing  15-3  kilos,  the  heat-production  of  which  was  22-3  calo- 
ries during  an  hour  previous  to  feeding,  was  given  1,200  grammes  of 
meat  at  noon.  The  heat-production  rose  to  36  calories  in  the  2nd  hour, 
and  42  calories  in  the  3rd.  It  remained  above  40  calories  per  hour 
beyond  the  loth  hour,  and  in  the  14th  hour  it  had  only  fallen  to  37  calo- 
ries, to  reach  25  calories  in  the  21st  hour.  On  the  whole,  the  increase 
in  heat-production  ran  parallel  with,  and  was  proportional  to,  the 
increase  in  the  excretion  of  nitrogen  (Wilhams,  Richie  and  Lusk). 
The  relatively  unimportant  sliare  taken  by  the  increased  work  of  the 
gastro-intestinal  tract  in  the  augmentation  of  the  metabolism  is  ihus- 
trated  by  the  fact  that  a  high  rate  of  heat -pro  duct  ion  was  maintained  tih 
the  14th  hour,  even  although  by  this  time  three-quarters  of  the  nitrogen 
corresponding  to  tlie  food  protein  had  been  eliminated  in  tlie  urine,  and 
the  work  of  digestion  and  absorption  must  have  been  largely  completed. 

The  rise  of  temperature  during  digestion  is  gradual,  the  ma.ximum 
being  reached  during  the  fourth  hour,  or  even  later. 

The  cause  of  the  daily  variation  of  temperature  has  been  nmch 
discussed.  There  is  no  doubt  that  several  factors  are  concerned, 
among  the  most  important  being  the  variation  in  the  amount  of 
contraction  of  the  skeletal  muscles  and  the  influence  of  food.     Mus- 


Fig.    216.- 


Curve  showing  the  Daily  Variation 
of  Body-Temperature. 


688 


ANIMAL  HEAT 


dZ5 
38 


3^ 


■3^5      ^S       i25     /f/t5     SJ 


1"  5 

;    U 

\, 

\ 

\, 

iff  li 

v 

"-^ 

^ 

cular  exercise  is  capable  of  causing  a  considerable  rise  in  the  tem- 
perature of  the  rectum  and  urine,  to  38*5°  C.  (101-3°  F.)  or  even 
38-9°  C.  (102°  F.)  without  producing  any  feeling  of  distress.  Other 
unknown  influences  seem  also  to  be  involved,  as  is  shown  by  the 
fact  that  in  persons  who  work  at  night  and  sleep  during  the  day 
the  curve  of  temperature,  although  greatly  altered,  is  not  reversed. 
Recent  observations  on  this  subject  are  those  of  Benedict.  By 
means  of  a  resistance  thermometer  in  the  rectum,  readings  were 

taken  usually  every  four  minutes. 
With  such  a  thermometer  no  disturb- 
ance of  the  person's  sleep  is  necessary 
to  obtain  a  reading.  He  can  sit  with- 
out discomfort  in  any  position,  walk 
about  the  room  (returning  to  the  ob- 
server's table  for  the  observations), 
and  even  ride  a  stationary  bicycle 
Even  years  of  night-work  do  not  elim- 
inate the  tendency  to  a  fall  of  tempera- 
ture at  night,  a  minimum  in  the  early 
morning,  and  a  morning  rise. 

As  to  the  relation  of  age  and  sex  to 
temperature,  it  is  only  necessary  to 
remark  that  the  mean  temperature 
both  of  the  young  child  and  of  the 
old  man  is  somewhat  higher  than 
that  of  the  vigorous  adult;  but  a 
point  of  more  importance  is  the  rela- 
tive imperfection  of  the  heat-regulation 
in  infancy  and  age,  and  the  greater 
effect  of  accidental  circumstances  on 
the  mean  temperature.  Thus,  old  people  and  young  children  are 
specially  liable  to  chills,  and  a  fit  of  crying  may  be  sufficient  to 
send  up  the  temperature  of  a  baby.  In  infants  an  hour  or  two  old 
the  temperature  may  be  as  low  as  34°  C  (93*2°  F.)  or  33*0°  C 
(91-4*'  F.)  even  when  they  are  fully  clothed  in  a  room  at  15°  C. 
(59°  F.).  It  rises  gradually  during  the  first  day  or  two,  but  shows 
marked  variations.  On  the  fifth  day  after  birth,  e.g.,  the  rectal 
temperature  ranged  from  36-2°  C  (97'i6°  F.)  to  33'5°  C.  (92-3°  F.) 
in  a  child  weighing  5^  pounds  (Babak).  The  temperature  of  women 
is  generally  a  little  higher  than  that  of  men,  and  is  also  somewhat 
more  variable.  A  fall  of  temperature,  rarely  amounting  to  more 
than  1°  F.,  is  associated  with  the  menstrual  period. 

After  death  the  body  cools  at  first  rapidly,  then  more  slowly 
(Fig.  217).  But  occasionally  a  post-mortem  rise  of  temperature 
may  take  place.  In  certain  acute  diseases  (like  tetanus)  associated 
with  excessive  muscular  contraction  this  has  been  especially  noticed; 
in  bodies  wasted  by  prolonged  illness  it  does  not  occur.     Nearly  an 


32 


30 


28 

Fig.  217. — Curve  of  Cooring  after 
Death  :  Guinea  -  Pig.  Time 
marked  along  horizontal,  and 
temperature  along  vertical  axis. 
At  a  ether  and  chloroform 
given  to  kill  animal;  death,  as 
indicated  by  stoppage  of  the 
heart,  took  place  at  b.  The 
dotted  line  shows  the  course 
the  curve  would  have  taken  if 
death  had  occurred  at  the 
moment  the  anaesthetics  were 
given.     Air  of  room  17-6"'. 


PRACTICAL  EXERCISES  689 

hour  after  dcaLh,  in  a  case  of  tetanus,  the  temperature  was  found 
to  be  45*3°,  while  before  death  it  was  447°  (W'underlich).  In  dogs 
a  shght  post-mortem  rise  may  be  demonstrated,  especialU'  when 
the  body  is  wrapped  up;  but  when  an  animal  has  been  long  under 
the  influence  of  anaesthetics  no  indication  whatever  of  the  phenom- 
enon may  be  obtained.  The  explanation  of  post-mortein  rise  of 
temperature  is  to  be  found:  (i)  In  the  continued  metabolism  of  the 
tissues  for  some  time  after  the  heart  has  ceased  to  beat,  for  the  cell 
dies  harder  than  the  body.  (2)  In  the  diminished  loss  of  heat,  due 
to  the  stoppage  of  tlic  circulation.  (3)  To  a  small  extent  in  physical 
changes  (rigor  mortis,  coagulation  of  blood)  in  which  heat  is  set  free. 


PRACTICAL  EXERCISES  ON  CHAPTERS  X.,  XL,  AND  XIL 

I.  Glycogen*— (i)  Preparation. — [a)  Cut  an  oyster  into  two  or  three 
pieces,  throw  it  into  boiling  water,  and  boil  for  a  minute  or  two.  Rub 
up  in  a  mortar  with  clean  sand,  and  again  boil.  Filter.  Precipitate 
any  proteins  which  have  not  been  coagulated,  by  adding  alternately 
a  drop  or  two  of  hydrochloric  acid  and  a  few  drops  of  potassio-mercuric 
iodide  so  long  as  a  precipitate  is  produced.  Only  a  small  cpiantity  of 
these  reagents  will  be  required,  as  the  greater  part  of  the  proteins  has 
been  already  coagulated  by  boiling.  Filter  if  any  precipitate  has  formed. 
The  filtrate  is  opalescent.  Precipitate  the  glycogen  from  the  filtrate  (after 
concentration  on  the  water-bath  if  it  exceeds  a  few  c.c.  in  bulk)  by  the 
addition  of  four  or  five  times  its  volume  of  alcohol.  Filter  off  the  precipi- 
tate, wash  it  on  the  filter  with  alcohol,  and  dissolve  it  in  a  little  water. 
To  some  of  the  solution  add  a  drop  or  two  of  iodine ;  a  reddish-brown 
(port  wine)  colour  is  produced,  which  disappears  on  heating,  returns  on 
cooling,  is  removed  by  an  alkali,  restored  by  an  acid.  Add  saliva  to  some 
of  the  glycogen  solution,  and  put  in  a  bath  at  40°  C.  In  a  few  minutes 
reducing  sugar  (maltose)  will  be  found  in  it  b}?-  Trommer's  test  (p.  10). 

Note  that  dextrin  (erythrodextrin)  gives  the  same  colour  with  iodine 
as  glycogen  does.  Dextrin  is  also  precipitated  by  alcohol,  but  a 
greater  proportion  must  be  added  to  cause  complete  precipitation. 
Glycogen  is  completely  precipitated  by  saturation  with  magnesium 
sulphate  or  ammonium  sulphate,  so  that  the  filtrate  no  longer  gives 
the  reddish  colour  with  iodine.  A  pure  solution  of  erji:hrodextrin  is 
not  precipitated.  On  the  addition  of  a  drop  or  two  of  a  solution  of 
basic  lead  acetate  to  a  solution  of  glycogen  in  distilled  water,  a  pre- 
cipitate forms  immediately.  When  the  same  reagent  is  added  to  a 
solution  of  dextrin  in  distilled  water  there  is  no  immediate  precipitate. 
Maltose  is  formed  when  dextrin  is  digested  with  sali\'a. 

{h)  Cut  another  oyster  into  pieces,  throw  it  into  boiling  water  acidu- 
lated with  dilute  acetic  acid,  and  boil  for  a  few  minutes.  Rub  up  in  a 
mortar  with  sand,  boil  again,  and  filter.  Test  a  portion  of  the  fil- 
trate with  iodine  for  glycogen.  Precipitate  the  rest  with  alcohol, 
filter,  dissolve  the  precipitate  in  water,  and  test  again  for  glycogen. 
On  boiling  some  of  the  opalescent  solution  for  a  few  minutes  after  the 
addition  of  a  few  drops  of  sulphuric  acid  the  opalescence  disappears,  and 

*  For  the  quantitative  estimation  of  glycogen  in  organs,  PtUiger's  methcMl 
is  the  best.  The  organ  is  minced  and  heated  with  strong  (60  per  cent.)  pota.s- 
sium  hydroxide  The  glycogen  is  precipitated  with  alcohol,  and  then,  alter 
livdrolysis  with  hvdroejiioric  acid,  estimated  as  dextrose. 

44 


r 


690  METABOLISM  AND  ANIMAL  HEAT 

when  the  sohition  has  been  neutralized  with  sodium  hydroxide  it  gives 
Trommer's  test,  owing  to  the  liydrolysis  of  the  glycogen  into  dextrose. 
(2)  Deeply  etherize  a  dog  or  rabbit  five  hours  after  a  meal  rich  in 
carbo-hydrates — e.g.,  rice  and  potatoes  in  the  case  of  the  dog,  carrots 
in  the  case  of  the  rabbit.  Fasten  it  on  a  holder.  Clip  oft  the  hair 
over  the  abdomen  in  the  middle  line.  Make  a  mesial  incision  through 
the  skin  and  abdominal  wall  from  the  ensiform  cartilage  to  the  pubis. 
The  liver  will  now  be  rapidly  cut  out  (by  the  demonstrator)  and  divided 
into  two  portions,  one  of  which  will  be  (distributed  among  the  class 
and)  treated  as  in  [a)  or  {b) ;  the  other  will  be  kept  for  an  hour  at  a 
temperature  of  40°  C.,  and  then  subjected  to  process  {a)  or  (6).  Little, 
if  any,  sugar  and  much  glycogen  will  be  found  in  the  portion  which 
was  boiled  immediately  after  excision.  Abundance  of  sugar  will  be 
found  in  the  portion  kept  at  40°  C. ;  it  may  or  may  not  contain  glycogen. 

2.  Catheterism. — In  many  physiological  experiments  it  is  necessary 
to  obtain  urine  from  the  bladder  by  means  of  a  catheter.  It  is  possible 
to  pass  a  fine  rubber  catheter  into  the  bladder  of  a  male  dog.  A 
larger  one  is  easily  passed  in  a  male  rabbit,  and  a  still  larger  in  a  bitch, 
which  is  often  used  for  experiments  on  metabolism.  Even  in  the  bitch 
the  opening  of  the  urethra  lies  entirely  concealed  within  the  vagina, 
much  deeper  than  the  cul-de-sac  in  the  mucous  membrane,  into  which 
the  beginner  usually  tries  to  force  the  catheter.  For  a  first  attempt 
the  animal  should  be  etherized  and  fastened  on  a  holder.  The  little 
or  index  finger  of  the  left  hand  is  passed  into  the  vagina  till  the  sym- 
physis pubis  can  be  felt.  A  little  below  this  is  the  opening  of  the 
urethra.  With  the  right  hand  the  point  of  a  catheter  of  suitable 
calibre  is  directed  along  the  finger,  and  after  a  little  '  guess  and  trial ' 
it  slips  into  the  bladder,  its  entrance  being  announced  by  the  escape  of 
urine.  A  glass  tube  drawn  out  to  a  sufficiently  small  calibre  and  bent 
near  the  point  is  the  easiest  form  of  catheter  to  pass  in  a  bitch.  The 
point  must,  of  course,  be  rounded  in  the  flame.  The  insertion  of  the 
catheter  is  much  facilitated  by  the  use  of  a  speculum. 

When  the  bitch  is  to  be  used  in  a  long  series  of  experiments  an 
operation  is  sometimes  performed  first  of  all  to  render  the  urethral 
orifice  more  accessible. 

3.  Glycosuria. — (i)  (a)  Weigh  a  dog  (female  by  preference)  or  rabbit. 
Fasten  on  a  holder,  and  etherize.  Insert  a  glass  cannula  into  the 
femoral  or  saphena  vein  of  the  dog,  or  into  the  jugular  of  the  rabbit 
(p.  212).  Fill  a  burette  with  a  2  per  cent,  solution  of  dextrose  in 
physiological  salt  solution,  connect  it  with  the  cannula  by  means  of  an 
indiarubber  tube,  taking  care  that  there  are  no  air-bubbles  in  the  tube, 
and  slowly  inject  as  much  of  the  solution  as  will  amount  to  J  or  |-  grm. 
of  sugar  per  kilo  of  body-weight.  Tie  the  vein,  remove  the  cannula,  and 
in  half  an  hour  evacuate  the  bladder  by  passing  a  catheter,  by  pressure 
on  the  abdomen,  or,  if  both  of  these  methods  fail,  by  tapping  the  bladder 
with  a  trocar  pushed  through  the  linea  alba  (suprapubic  puncture). 
In  an  hour  again  draw  off  the  urine.     Test  both  specimen-,  for  sugar. 

In  this  experiment  the  opportunity  may  also  be  taken  to  demon- 
strate that  egg-albumin,  when  injected  into  the  blood,  is  excreted  by 
the  kidneys,  a  filtered  solution  containing  the  albumin  of  one  egg  and 
sugar  in  the  quantity  mentioned  being  injected. 

The  catheter  may  be  inserted  before  the  injection  is  begun,  and  the 
bladder  evacuated.  After  the  injection  the  urine  that  drops  from  the 
catheter  may  be  collected  in  test-tubes,  first  every  two  minutes,  and 
then,  as  soon  as  sugar  is  found,  every  ten  minutes.  Determine  the 
interval  between  injection  and  the  appearance  of  the  first  trace  of 
sugar  and  albumin.     If  a  sufficient  amount  of  urine  is  obtained,  the 


PRACTICAL  EXERCISES  691 

quantity  of  sugar  in  successive  specimens  may  be  estimated  and  com- 
pared. The  rate  of  flow  of  the  urine  as  measured  by  the  number  of 
drops  falling  from  the  catheter  may  also  be  estimated  from  time  to  time 
in  order  to  dctcnninc  whether  diuresis  is  taking  place. 

If  a  rabbit  is  used  for  this  experiment,  the  sugar  solution  may  be 
injected  into  the  ear  vein.  '1  he  vein  is  caused  to  swell  up  by  pressing 
on  it  with  the  finger  and  thumb,  and  the  hypodermic  needle  is  then 
inserted  towards  the  heart. 

(h)  Instead  of  collecting  the  urine  by  a  catheter  in  the  bladder,  the 
abdomen  of  the  dog  may  be  opened,  and  a  cannula  lied  into  each  ureter. 
The  two  cannuUe  are  then  connected  by  short  rubber  tubes  with  a 
glass  Y-piece,  on  the  stem  of  which  a  test-tube  is  tied  for  collecting  the 
urine.  Replace  the  test-tube  by  a  fresh  one  from  time  to  time.  The 
urine  already  in  the  bladder  is  removed  by  pressure  or  by  a  trocar,  and 
tested  for  sugar,  since  the  aneesthetic  itself  may  cause  a  certain  amount 
of  glycosuria.  Test  the  samples  of  urine  obtained  from  the  ureters 
for  sugar,  and  in  those  in  which  it  is  present  estimate  its  amount.  Note 
also  any  changes  in  the  rate  of  secretion  of  urine,  and  any  abnormal 
constituents,  as  albumin. 

(2)  Phlorhizin  Glycosuria. — Dissolve  \  grm.  of  phlorhizin  in  warm 
water,  and  inject  it  subcutaneously  into  a  rabbit.  Obtain  a  sample  of 
the  urine  at  the  end  of  two  hours,  by  pressure  on  the  abdomen  with 
the  thumb  or  by  passing  a  catheter,  and  test  for  sugar.  If  none  is 
present,  wait  some  time  longer,  and  again  test  the  urine. 

This  experiment  can  also  be  performed  without  risk  on  man.  One 
grm.  of  phlorhizin  has  been  injected  twice  a  day  without  disturbing  the 
individual.  Much  sugar  is  found  in  the  urine,  but  it  disappears  the 
day  after  the  administration  of  phlorhizin  is  stopped.  The  phlorhizin 
may  also  be  given  by  the  mouth,  but  more  is  required,  and  it  is  not 
very  easily  absorbed,  and  often  causes  diarrhoea  (v.  Mering). 

(3)  Alimentary  Glycosuria. — The  urine  having  been  tested  for  sugar 
for  two  successive  days,  and  none  being  found — 

(fl)  A  large  quantity  of  dextrose  is  to  be  taken  in  the  form  which  is 
most  agreeable  to  the  student  some  hours  after  a  meal.  The  urine  of 
the  next  twenty-four  hours  is  to  be  collected  and  measured.  A  sample 
of  it  is  then  to  be  tested  for  reducing  sugar  by  Trommer's  and  the 
phenyl-hydrazine  test.  If  any  sugar  is  found,  the  reducing  power  of  a 
definite  quantity  of  the  urine  is  to  be  determined  by  titration  with 
Fehling's  solution  (p.  318). 

(6)  Instead  of  dextrose  use  cane-sugar  and  proceed  as  in  (a).  But 
estimate  the  reducing  power  of  the  urine  {")  before  and  (/3)  after  boiling 
with  hydrochloric  acid  (p.  459). 

■  (c)  A  large  meal  of  rice  and  arrowroot,  sweetened  with  as  much  dex- 
trose as  the  observer  can  induce  himself  to  swallow,  is  to  be  taken,  and 
the  urine  treated  as  in  (a). 

{d)  A  large  number  of  sweet  oranges  may  be  eaten.* 

4.  Milk. — (i)  Examine  a  drop  of  fresh  cow's  milk  with  the  micro- 
scope.    Note  the  fat  globules  of  various  sizes. 

(2)  Determine  the  specific  gravity  of  the  milk  with  a  hydrometer 
(lactometer).  Then  centrifugalize  some  of  the  milk  to  separate  the 
cream,  which  rises  to  the  top  of  the  tubes.  Remove  the  cream  and 
determine  the  specific  gravity  of  the  skimmed  milk.  It  will  be  found 
to  have  increased,  since  the  fat  is  of  lower  specific  gravity  than  the  rest 
of  the  milk.  Normal  cow's  milk  has  a  specific  gravity  of  1,0 j8  to 
1,034,  skimmed  milk  1,033  to  1,037. 

*  Thc-e  experiments  may  be  distributed  among  the  class  so  that  each 
student  does  one 


692  METABOLISM  AND  ANIMAL  HEAT 

(3)  Pest  the  reaction  of  the  milk  to  litmus-paper.    It  is  slightly  alkaline. 

(4)  (fl)  Put  10  c.c.  of  milk  in  a  test-tube,  and  nearly  fill  it  up  with 
water.  Add  strong  acetic  acid  drop  by  drop.  A  precipitate  of  casein- 
ogen  is  thrown  down  which  entangles  the  fat,  and  carries  it  down 
mechanically  along  with  it.  Filter  off  the  precipitate.  Keep  the 
filtrate  for  [b).  Wash  the  precipitate  with  water,  scrape  a  portion  of 
it  off  the  filter,  and  add  to  it  some  2  per  cent,  sodium  carbonate  solution. 
The  caseinogen  dissolves,  while  the  fat  remains  in  suspension.  The 
solution  gives  the  colour  reactions  for  proteins  (p.  8). 

(6)  Test  some  of  the  filtrate  (p.  10)  for  lactose.  Add  dilute  sodium 
carbonate  solution  to  another  portion  till  it  is  only  slightly  acid.  Boil, 
and  lactalbumin  is  coagulated.  Remove  the  lactalbumin  by  filtering, 
and  test  this  filtrate  for  earthy  (i.e.,  calcium  and  magnesium)  phos- 
phates by  adding  a  few  drops  of  ammonia,  which  precipitates  them  as 
a  slight  cloud. 

(c)  To  5  c.c.  of  milk  add  an  equal  volume  of  saturated  ammonium 
sulphate  solution.  The  caseinogen  is  precipitated,  entangling  the  fat. 
Filter  off.  The  filtrate  may  be  used  to  test  for  lactalbumin  by  boiling. 
The  addition  of  water  to  tlie  precipitate  of  caseinogen  (and  fat)  on  the 
filter  causes  the  caseinogen  to  dissolve,  as  it  is  soluble  in  weak  salt 
solutions.  Caseinogen  can  also  be  precipitated  by  saturating  milk 
with  sodium  chloride  or  magnesium  sulphate. 

(5)  To  5  c.c.  of  milk  add  a  couple  of  drops  of  20  per  cent,  sodium  or 
potassium  hydroxide,  and  then  a  few  c.c.  of  ether.  Shake  up.  The 
ether  dissolves  the  fat,  and  the  opacity  of  the  milk  diminishes.  Take 
off  the  ether  with  a  pipette,  evaporate  away  most  of  it  on  a  water-bath, 
and  place  a  drop  or  two  of  the  remainder  on  a  filter-paper.  A  greasy 
stain  is  left,  showing  the  presence  of  the  fat  of  the  milk,  or  butter. 

(6)  Clotting  of  Milk. — (a)  To  a  few  c.c.  of  milk  in  a  test-tube  add  a 
few  drops  of  rennet.  Place  the  tube  in  a  bath  at  40°  C.  In  a  short 
time  a  clot  or  curd  is  formed,  consisting  of  casein,  which  is  derived  from 
the  caseinogen.  The  fat  is  entangled  in  the  clot.  On  standing  some 
time  the  clot  contracts,  and  exudes  the  whey.  Boil  some  of  the  whey 
after  slight  acidulation  with  acetic  acid;  the  lactalbumin  and  whey- 
protein  are  coagulated.  Test  another  portion  of  whey  for  proteins  by 
one  of  the  general  protein  tests  (p.  8)— e.g.,  the  xanthoproteic. 

U})  Repeat  [a)  but  use  rennet  which  has  been  previously  boiied.  The 
milk  is  not  curdled,  because  the  ferment  has  been  inactivated  by  boiling. 

(c)  To  10  c.c.  of  milk  add  3  c.c.  of  i  per  cent,  potassium  oxalate. 
Divide  the  oxalated  milk  into  three  portions — A,  B,  and  C.  To  A  add 
a  few  drops  of  rennet,  to  B  i  c.c.  of  2  per  cent,  calcium  chloride  solu- 
tion and  a  little  rennet,  and  to  C  i  c.c.  of  2  per  cent,  calcium  chloride 
solution  alone.  Put  the  tubes  at  40°  C.  Clotting  will  occur  in  B,  but 
not  in  A  or  C. 

5.  Cheese. — (i)  Rub  up  some  finely -grated  cheese  in  a  mortar  with 
2  per  cent,  sodium  carbonate  solution.  Filter.  The  filtrate  contains 
casein,  which  can  be  precipitated  by  adding  dilute  acetic  acid  by  drops 
to  a  portion  of  the  filtrate.  The  precipitate  is  soluble  in  excess  of  the 
acid.  With  another  portion  of  the  filtrate  perform  some  of  the  general 
protein  tests  (p.  8). 

(2)  Shake  up  some  finely-grated  cheese  in  a  dry  test-tube  with  ether. 
Take  off  the  ether  with  a  pipette,  and  evaporate  on  a  water-bath  till 
only  a  few  drops  remain.  With  a  glass  rod  put  a  drop  of  the  ether  on 
a  piece  of  filter-paper.     A  greasy  spot  is  left,  showing  that  fat  is  present. 

6.  Flour. — (i)  Mix  some  wheat-flour  with  a  little  water  into  a  stiff 
dough.  Let  it  s-tand  for  a  few  minutes  at  body-temperature  to  facilitate 
the  formation  of  gluten.     Wrap  a  piece  in  cheese-cloth,  forming  a  kind 


PRACTICAL  EXERCISES  693 

of  bag,  and  knead  it  with  the  fingers  in  a  capsule  of  water.  The 
starcli  grains  come  through  the  cheese-cloth.  Pour  tlie  water  into  a 
beaker.  It  is  opaque,  and  on  standing  the  starch  grains  sink  to  the 
bottom,  [a)  Test  for  starch  with  the  iodine  test,  and  also  examine 
microscopically.  The  grains  are  round,  with  a  central  hilum,  and  are 
smaller  than  those  of  potato  starch  (p.  11).  {b)  Test  for  sugar  by 
Trommer's  test  (p.  10).  None  is  present  unless  the  flour  has  been  made 
from  inferior  grain  in  which  some  germination  has  taken  place. 

(2)  Go  on  kneading  the  dough  till  no  more  starch  comes  through. 
The  sticky  mass  which  remains  in  the  bag  is  a  protein  called  gluten, 
which  is  formed  from  certain  globulins  and  other  proteins  in  the  flour 
on  addition  of  water.  Oatmeal,  ground  rice,  and  other  grains  poor  in 
gluten-forming  globulins  do  not  form  dough  when  mixed  with  water. 
Suspend  some  of  the  gluten  in  water  in  a  test-tube,'  and  apply  to  it  the 
general  protein  colour  tests  (p.  8). 

7.  Bread. — (i)  Rub  up  a  small  piece  of  the  crumb  of  a  stale  loaf  in  a 
mortar  with  water.  Strain  through  cheese-cloth.  The  fluid  which 
passes  through  contains  starch  grains,  {a)  Filter  it,  and  test  a  portion 
of  the  filtrate  for  dextrose  by  Trommer's  test.  A  positive  result 
is  obtained.  Test  another  portion  with  iodine  for  erythrodextrin. 
{b)  Test  a  portion  of  the  residue  of  the  bread  which  has  not  passed 
through  the  cheese-cloth  for  protein  by  the  general  protein  tests — e.g., 
the  xanthroproteic  or  Millon's  tests. 

(2)  Repeat  (i)  using  the  crust  of  the  bread.  Both  dextrose  and 
erythrodextrin  are  present  in  the  cold-water  extract,  but  the  dextrose 
is  less  plentiful  than  in  the  crumb,  having  been  converted  into  caramel 
in  the  baking.  The  sugar  and  dextrin  are  formed  from  the  starch  of  the 
flour  by  the  ferments  of  the  yeast  employed  to  make  the  bread  rise. 

8.  Variations  in  the  Total  Nitrogen  (p.  514)  and  in  the  Quantity  of 
Urea  excreted,  with  Variations  in  the  Amount  of  Proteins  in  the  Food. — 
The  student  should  put  himself,  or  somebody  else  if  he  can,  for  two  day.s 
on  a  diet  poor  in  proteins,  then  (after  an  interval  of  forty-eight  hours 
on  his  ordinary  food)  for  two  days  on  a  diet  rich  in  proteins.  A  suitable 
table  of  diets  will  be  supplied.  The  urine  should  be  collected  on  the 
six  days  of  the  period  of  experiment,  on  the  day  before  it  begins,  and 
on  the  day  after  it  ends.  Small  samples  of  the  mixed  urine  of  the 
twenty-four  hours  for  each  of  these  eight  days  should  be  brought  to  the 
laboratory,  and  the  quantity  of  urea  determined  by  the  hypobromite 
method.  The  volume  of  the  urine  passed  in  each  interval  of  twenty- 
four  hours  being  known,  the  total  excretion  of  urea  for  the  twenty-four 
hours  can  be  calculated,  and  a  curve  plotted  to  show  how  it  varies 
during  the  period  of  experiment.*  If  sufticient  time  is  available,  the 
experiment  will  be  made  still  more  instructive  by  determining  the 
total  nitrogen  in  each  sample  in  addition  to  the  urea.  A  curve  showing 
the  variation  in  the  total  nitrogen  can  then  be  plotted  on  the  same  paper 
as  the  urea  curve,  and  a  table  calcidatcd  giving  the  percentage  of  the 
total  nitrogen  contained  in  the  urea  for  each  day  of  the  experiment. 

9.  Action  of  Epinephrin  (Adrenalin). — Several  experiments  to  illus- 
trate this  are  given  in  the  I'ractical  Exercises  following  other  chapters, 
but  may  etpially  well  be  performed  here.  (See  Experiment  8,  p.  66; 
Experiment  3,  ip.  447.) 

♦  In  17  healthy  students  the  average  amount  of  urea  excreted  in  twenty 
four  hours  on  the  ordinary  diet  was  29-51  grammes  (minimum  I9'35  grammes 
maximum  .j(Voi  grammes);  on  a  diet  poor  in  protein,  avorat^e  2(>'75  grammes 
(minimum  952  grammes,  maximum  3286  grammes) ;  on  a  diet  rich  in  protein, 
average  38-83  grammes  (minimum  23-26  grammes,  maximum  07-82  grammes).' 


694  METABOLISM  AND  ANIMAL  HEAT 

lo.*  Measurement  of  the  Quantity  of  Heat  given  off  in  Respiration. — 

This  may  be  done  approximately  as  follows:  Put  in  the  inner  copper 
vessel,  A,  of  the  calorimeter  shown  in  Fig.  213  (p.  658)  a  measured 
quantity  of  water  sufficient  to  completely  cover  the  series  of  brass  discs. 
Place  A  in  the  wide  outer  cylinder,  the  bottom  of  which  it  is  prevented 
from  touching  by  pieces  of  cork.  The  outer  cylinder  hinders  loss  of 
heat  to  the  air.  Suspend  a  thermometer  in  the  water  through  one  of  the 
holes  in  the  lid.  In  the  other  hole  place  a  glass  rod  to  serve  as  a  stirrer. 
Read  off  the  temperature  of  the  water.  Put  the  glass  tube  connected 
with  the  apparatus  in  the  mouth,  and  breathe  out  through  it  as  regu- 
larly and  normally  as  possible,  closing  the  opening  of  the  tube  with 
the  tongue  after  each  expiration  and  breathing  in  through  the  nose. 
Continue  this  for  five  or  ten  minutes,  taking  care  to  stir  the  water  fre- 
quently. Then  read  oif  the  temperature  again.  If  W  be  the  quantity 
of  water  in  c.c,  and  t  the  observed  rise  of  temperature  in  degrees  Centi- 
grade, W^  equals  the  quantity  of  heat,  expressed  in  small  calories 
(p.  653),  given  off  by  the  respiratory  tract  in  the  time  of  the  experiment, 
on  the  assumptions  (i)  that  all  the  heat  has  been  absorbed  by  the  water, 
(2)  that  none  of  it  has  been  lost  by  radiation  and  conduction  from  the 
calorimeter  to  the  surrounding  air.  Calculate  the  loss  in  twenty-four 
hours  on  this  basis;  then  repeat  the  experiment,  breathing  as  rapidly 
and  deeply  as  possible,  so  as  to  increase  the  amount  of  ventilation. 
The  quantity  of  heat  given  off  will  be  found  to  be  increased,  t 

In  an  experiment  of  short  duration  (2)  is  approximately  fulfilled. 
As  to  (i),  it  must  be  noted  that  in  the  first  place  the  metal  of  the 
calorimeter  is  heated  as  well  as  the  water,  and  the  water-equivalent 
of  the  apparatus  must  be  added  to  the  weight  of  the  water  (p.  653). 
The  water-equivalent  is  determined  by  putting  a  definite  weight  of 
water  at  air  temperature  T  into  the  calorimeter,  and  then  allowing  a 
quantity  of  hot  water  at  known  temperature  T'  to  run  into  it,  stirring 
well,  and  noting  the  temperature  of  the  water  when  it  has  ceased  to 
rise.  Call  this  temperature  T".  Enough  hot  water  should  be  added 
to  raise  the  temperature  of  the  calorimeter  about  2°  C.  The  quantity 
run  in  is  obtained  by  weighing  the  calorimeter  before  and  after  the 
hot  water  has  been  added.  Suppose  it  is  m.  Let  the  mass  of  the  cold 
water  in  the  calorimeter  at  first  be  M,  and  let  M'=the  mass  of  water 
which  would  be  raised  1°  C.  in  temperature  by  a  quantity  of  heat  suffi- 
cient to  increase  the  temperature  of  all  the  metal,  etc.,  of  the  calorimeter 
by  i' — in  other  words,  the  water-equivalent  of  the  calorimeter. 

The  mass  m  of  hot  water  has  lost  heat  to  the  amount  of  m  (T' — T"), 
and  this  has  gone  to  raise  the  temperature  of  a  mass  of  water  M, 
and  metal  equivalent  to  a  mass  of  water  M',  by  (T" — T)  degrees. 
...  m  (T'— T")  =  M(T"— T)  -f-  M'(T"— T).  Everything  in  this  equation 
except  M'  is  known,  and  .".  M',  the  water-equivalent  of  the  calorhneter, 
can  be  deduced,  and  must  be  added  in  all  exact  experiments  to  the  mass 
of  water  contained  in  it. 

Secondly,  all  the  excess  of  heat  in  the  expired  over  that  in  the  inspired 
air  is  not  given  off  to  the  calorimeter,  for  the  air  passes  out  of  it  at  a 
slightly  higher  temperature  than  that  of  the  atmosphere.  At  the 
beginning  of  the  experiment  this  excess  of  temperature  is  zero.  If 
at  the  end  it  is  1°  C,  the  mean  excess  is  0*5°  C.     Now,  when  respiration 

*  This  experiment  is  given  as  an  example  of  a  simple  calorimetric  measure- 
ment, which  can  be  easily  performed  with  sufficient  accuracy  by  students, 
and  involves  the  essential  principles  of  such  determinations. 

t  The  average  lieat-loss  l)y  the  hings  for  31  men  (calculated  for  the  24  hours) 
was  312,000  small  calories  for  normal,  919,000  for  the  fastest,  and  195,000  for 
the  slowest  breathing 


PRACTICAL  EXERCISES 


695 


is  carried  on  in  a  room  at  a  temperature  of  10°  C,  the  expired  air  has 
its  temperature  increased  by  nearly  30°  C.  About  ^(j  of  the  heat 
given  off  by  tlie  respiratory  tract  in  raising  the  temperature  of  the  air 
of  respiration  would  accordingly  be  lost  in  such  an  experiment.  But 
since  the  portion  of  the  heat  lost  by  the  lungs  which  goes  to  heat  the 
expired  air  is  only  J  of  the  whole  heat  lost  in  respiration  (p.  658),  the 
error  would  only  amount  to  =j,y,y  of  the  whole,  and  this  is  negligible. 

Thirdly,  the  air  leaves  the  calorimeter  saturated  with  watery  vapour 
at,  say.  10-5°,  while  the  inspired  air  is  not  saturated  for  10"  C.  Now, 
the  quantity  of  heat  rendered  latent  in  the  evaporation  of  water  suffi- 
cient to  Saturate  a  given  quantity  of  air  at  40°  C.  (the  expired  air  is 
saturated  for  body-temperature)  is  six  times  that  required  to  saturate 
the  same  quantity  of  air  at  10°.  If,  then,  the  inspired  air  is  half 
saturated,  the  error  under  this  head  is  ^.^,  or  8^  per  cent.  If  the  inspired 
air  is  three-quarters  saturated,  the  error  is  l}^,  or  about  4  per  cent.  If  the 
air  is  fully  saturated  before  inspiration,  as  is  the  case  when  it  is  drawn 
in  through  a  water-valve  (Fig.  218)  by  a  tube  fi.xed  in  one  nostril,  the 
only  error  is  that  due  to  the  slight  excess  of  temperature  of  the  air 
leaving  the  calorimeter  over  that  of  the  inspired  air.  The  latent  heat 
of  the  aqueous  vapour  in  saturated  air  at  iO'5°  C.  is  about  5'j  more 
than  the  latent  heat  of  the  aqueous  vapour  in  the  same 
mass  of  saturated  air  at  10°  C,  or  about  ,J,j  of  the 
latent  heat  in  saturated  air  at  40^.  The  error  in  this 
case  would  therefore  be  under  i  percent.  The  tubes 
must  be  wide  and  the  bottle  large. 

II.  In  the  observations  on  the  blood-flow  in  the 
hands  (Experimen  32,  p.  218)  data  on  the  quantity 
of  heat  given  off  by  the  hands  when  immersed  in  water 
at  a  given  temperature  have  already  been  obtained. 
Additional  data  should  be  got  by  putting  the  hand 
into  the  calorimeter  without  previous  immersion  in 
the  bath,  and  comparing  the  heat  given  off  during 
the  period  when  the  hand  is  acquiring  the  temperature 
of  the  calorimeter  with  that  given  off  when  the  steady 
state  has  been  reacted.  Different  calorimeter  tem- 
peratures should  be  employed.  It  will  be  found  that 
as  the  calorimeter  temperature  is  diminished  the 
quantity  of  heat  given  off  may  be  increiised  although 
the  blood-flow  is  diminished,  eacli  gramme  of  blood  passing  through 
the  hand  giving  off  more  heat  the  lower  the  calorimeter  temperature. 

The  quantity  of  heat  lost  by  the  h  md,  at  a  given  temperature 
of  the  calorimeter,  per  square  centimetre  of  skin  surface  can  be  cal- 
culated. If  no  special  instrument  for  measuring  the  area  of  irregular 
surfaces  is  available,  the  surface  of  the  hand  can  be  arrived  at  ap- 
proximately by  covering  it  with  strips  of  gummed  paper  of  known 
breadth,  and  noting  the  length  used  to  cover  the  whole  hand  up  to  the 
lower  level  of  the  styloid  process  of  the  ulna.  Or  an  old  thin  glove 
which  fits  the  hand  can  be  cut  off  at  this  level  and  weighed.  As  large 
a  piece  as  possible  of  regular  shape  is  then  cut  from  the  glove,  weighed, 
and  its  area  deduced  by  measuring  it  with  a  rule.  The  area  of  the 
whole  glove,  on  the  assumption  that  it  is  of  uniform  thickness,  is  thus 
known.  Or,  without  cutting  the  glove,  it  may  be  laid  flat  on  a  piece 
of  paper,  an  outline  of  it  traced,  and  the  paper  cut  out.  Tlie  weight 
of  the  paper  cut  out  is  compared  with  that  of  a  piece  of  paper  of  known 
area,  and  its  area  deduced.  Obviously  this  is  approximately  equal  to 
half  the  surface  of  the  hand. 


Fig.  218.  — Bottle 
arranged  for 
Water-Valve. 


CHAPTER  XIII 

THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Section   I.  —  Preliminary   Observations  —  Physical  and 
Technical  Data. 

In  all  the  great  functions  of  the  body  muscular  movements  play 
an  essential  part.  The  circulation  and  the  respiration,  the  two 
functions  most  immediately  essential  to  hfe,  are  kept  up  by  the 
contraction  and  relaxation  of  muscles.  The  movements  of  the 
digestive  canal,  the  regulation  of  the  blood-supply  to  its  glands  and 
to  all  parts  of  the  body,  and  that  immense  class  of  movements 
which  we  call  voluntary,  are  all  dependent  upon  muscular  action, 
which,  again,  is  indebted  for  its  initiation,  continuance,  or  control, 
to  impulses  passing  along  the  nerves  from  the  nerve-centres. 
Hitherto  we  have  not  gone  below  the  surface  fact,  that  muscular 
fibres  have  the  power  of  contracting,  either  automatically,  or  in 
response  to  suitable  stimuli.  In  this  chapter  and  the  two  next  we 
shall  consider  in  detail  the  general  properties  of  muscle,  nerve,  and 
the  other  excitable  tissues. 

Lying  deeper  than  the  peculiarities  of  individual  muscles,  muscular 
tissue  has  certain  common  properties — physical,  chemical,  and 
physiological.  The  biceps  muscle  flexes  the  arm  upon  the  elbow, 
and  the  triceps  extends  it.  The  external  rectus  rotates  the  eyeball 
outwards.  The  intercostal  muscles  elevate  the  ribs.  The  sphincter 
ani  seals  up  by  a  ring-like  contraction  the  lower  end  of  the  ahmentary 
canal.  These  actions  are  very  different,  but  the  muscles  that  carry 
them  out  are  at  bottom  very  similar.  And  it  cannot  be  doubted 
that  the  functional  differences  are  due  entirely,  or  almost  entirely, 
to  differences  of  anatomical  connection,  on  the  one  hand  with  bones 
and  tendons,  on  the  other  with  the  nerve-cells  of  the  spinal  cord  and 
brain  The  common  properties  in  which  all  the  skeletal  muscles 
agree  are  the  subject-matter  of  the  general  physiology  of  striated 
muscle. 

The  cardiac  muscle  differs  more,  both  in  structure  and  in  function, 
from  the  sk(;letal  muscles  than  these  do  among  themselves;  the 
smooth  muscle  of  the  intestines  and  bloodvessels  still  more.  But 
('vei"y  muscular  fibre,  striped  or  unsLriped,  resembles  every  other 

G96 


PRELIMINARY  DATA 


697 


muscular  fibre  more  than  it  does  a  nerve-fibre  or  a  gland-cell  or  an 
epithelial  scale.  The  properties  common  to  all  nmsclc  make  up  the 
general  physiology  of  muscular  tissue. 

A  nerve-fibre  is  at  first  sight  very  different  from  a  muscular  fibre. 
It  has  diverged  more  widely  from  the  primitive  type  of  undiffer- 
entiated protoplasm,  but  it  retains,  in  common  with  the  musde- 
fibre,  susceptibility  to  stimulation,  or  excitability,  the  capacity  for 
growth,  and  to  a  limited  extent  the  capacity  for  reproduction  ;  and 
while  it  has  lost  the  power  of  contraction  or  contractility,  it  has 
developed  in  a  higher  degree  than  any  other  tissue  the  power  of 
conducting  the  excited  state.  This  inheritance  of  primitive  pro- 
perties, retained  alike  by  both  tissues,  is  the  basis  of  the  general 
physiology  of  muscle  and  nerve. 

The  electrical  organ  of  Torpedo  01  Malapterurus  is  inter- 
mediate in  some  respects  between  muscle  and  nerve,  and  has 
properties  common  to  both.  In  the  gland-cell  the  chemical  powers 
of  native  protoplasm  have  been  specialized  and  developed.  Con- 
tractility has  been,  in  general,  entirely  lost ;  but  excitabihty  remains. 
The  idea  that  certain  common  en- 
dowments find  expression  in  the 
action  of  muscle,  nerve,  electrical 
organ,  gland,  etc.,  in  the  midst 
of  all  their  apparent  differences,  is 
the  basis  of  the  general  physiology 
of  the  excitable  tissues. 

It  is  impossible  to  understand  the 
general  physiology  of  muscle  and 
nerve  without  some  acquaintance 
with  electricity.  It  would  be  out  of 
place  to  give  even  a  complete  sketch 
of  this  preliminary  but  essential 
knowledge  here;  and  the  student  is  expressly  warned  that  in  this  book 
the  elementary  facts  and  principles  of  physics  are  assumed  to  be  part 
of  his  mental  outfit.  But  in  describing  some  of  the  electrical  apparatus 
most  commonly  used  in  the  study  of  this  portion  of  our  subject,  and 
which  are  employed  in  the  Practical  Exercises,  it  may  be  useful  to  recall 
some  of  the  physical  facts  involved. 

Batteries. — The  Danicll  cell  is  perhaps  better  suited  for  physiological 
work  than  any  other  voltaic  element,  although  for  special  purposes 
Grove,  Leclanche,  bichromate  of  potassium  or  dry  lotteries  may  be 
employed  (p.  195).  Storage  batteries  or  current  from  the  street  supply 
may  also  be  used. 

Inside  the  Daniell  cell  the  current  (the  positive  electricity)  passes 
from  zinc  to  copper;  outside,  from  copper  to  zinc.  The  copper  is  called 
the  positive,  the  zinc  the  negative,  pole.  When  the  current  is  passed 
through  a  tissue,  the  electrode  by  which  it  enters  is  termed  the  anode, 
and  that  by  which  it  leaves  the  tissue  the  kathode.  The  anode  is, 
therefore,  the  electrode  connected  with  the  copper  of  the  Daniell's  cell; 
the  kathode  is  connected  with  the  zinc. 

Potential — Current  Strength — Resistance. — \Vc  do  not  know  what 
in  reality  electricity  is,  but  we  do  know  tiuit  when  a  current  flows  along 


Fig.  219. — Daniell  Cell.  A,  outer  vessel; 
B,  copper;  C,  porous  pot;  D,  zinc  rod; 
D  is  supposed  to  be  raised  a  little  so  as 
to  be  seen. 


698        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

a  wire  energy  is  expended,  just  as  energy  is  expended  when  water  flows 
from  a  higher  to  a  lower  level.  Many  of  the  phenomena  of  current 
electricity  can,  in  fact,  be  illustrated  by  the  laws  of  flow  of  an  incom- 
pressible liquid.  The  difference  of  level,  in  virtue  of  which  the  flow 
of  liquid  is  maintained,  corresponds  to  the  difference  of  electrical  level, 
or  potential,  in  virtue  of  which  an  electrical  current  is  kept  up.  The 
positive  pole  of  a  voltaic  cell  is  at  a  higher  potential  than  the  negative. 
When  they  are  connected  by  a  conductor,  a  flow  of  electricity  takes 
place,  which,  if  the  difference  of  level  or  potential  were  not  constantly 
restored,  would  soon  equalize  it,  and  the  current  would  cease;  just  as 
the  flow  of  water  from  a  reservoir  would  ultimately  stop  if  it  was  not 
replenished.  If  the  reservoir  was  small,  and  the  discharging-pipe  large, 
the  flow  would  only  last  a  short  time;  but  if  water  was  constantly  being 
pumped  up  into  it,  tlie  flow  would  go  on  indefinitely.  This  is  prac- 
tically the  case  in  the  Daniell  cell.  Zinc  is  constantly  being  dissolved, 
and  the  chemical  energy  which  thus  disappears  goes  to  maintain  a 
constant  difference  of  potential  between  the  poles.  Electricity,  so  to 
speak,  is  continually  running  down  from  the  place  of  higher  to  the  place 
of  lower  potential,  but  the  cistern  is  always  kept  full. 

The  difference  of  electrical  potential  between  two  points  is  called 
the  electrotnotive  force;  and  from  its  analogy  with  difference  of  pressure 
in  a  liquid,  it  is  easy  to  understand  that  the  intensity  or  strength  of  the 
current — that  is,  the  rate  of  flow  of  the  electricity  between  two  points  of 
a  conductor — does  not  depend  upon  the  electromotive  force  alone, 
any  more  than  the  rate  of  discharge  of  water  from  the  end  of  a  long 
pipe  depends  alone  on  the  difference  of  level  between  it  and  the  reser- 
voir. In  both  cases  the  resistance  to  the  flow  must  also  be  taken  account 
of.  With  a  given  difference  of  level,  more  water  will  pass  per  second 
through  a  wide  than  through  a  narrow  pipe,  for  the  resistance  due  to 
friction  is  greater  in  the  latter.  In  the  case  of  an  electrical  current,  a 
wire  connecting  the  two  poles  of  a  Daniell's  cell  will  represent  the  pipe. 
A  thick  short  wire  has  less  resistance  than  a  thin  long  wire;  and  for  a 
given  difference  of  potential,  of  electric  level,  a  stronger  current  will 
flow  along  the  former.  But  for  a  wire  of  given  dimensions,  the  in- 
tensity of  the  current  will  vary  with  the  electromotive  force.  The 
relation  between  electromotive  force,  strength  of  current,  and  resistance 

were  experimentally   determined   by   Ohm,   and   the  formula    C=  i^> 

which  expresses  it,  is  called  Ohm's  Law.  It  states  that  the  current 
varies  directly  as  the  electromotive  force,  and  inversely  as  the  resist- 
ance. 

For  the  measurement  of  electrical  quantities  a  system  of  units  is 
necessary.  The  common  unit  of  resistance  is  the  ohm,  of  current 
the  ampdre,  of  electromotive  force  the  volt.  The  electromotive  force 
of  a  Daniell's  cell  is  about  a  volt.  An  electromotive  force  of  a  volt, 
acting  through  a  resistance  of  an  ohm,  yields  a  current  of  one  ampere. 
But  the  current  produced  by  a  Daniell's  cell,  with  its  poles  connected 
by  a  wire  of  i  ohm  resistance,  would  be  less  than  an  ampere,  because 
the  internal  resistance  of  the  cell  itself — that  is,  the  resistance  of  the 
liquids  between  the  zinc  and  the  copper — must  be  added  to  the  external 
resistance  in  order  to  get  the  total  resistance,  which  is  the  quantity 
represented  by  R  in  Ohm's  Law. 

Measurement  of  Resistance. — To  find  the  resistance  of  a  conductor, 
we  compare  it  with  known  resistances,  as  a  grocer  finds  the  weight  of  a 
packet  of  tea  by  comparing  it  with  known  weights.  Tlie  Wheatstone's 
bridge  method  of  measuring  resistance  depends  on  the  fact  that  if  four 
resi.stances,  AB,  AD,  BC,  CD,  are  connected,  as  in  Fig.  220,  with  each 


PRELIMINARY  DATA 


699 


other,  and  with  a  galvanometer,  G,  and  a  battery,  F,  no  current  wiU 

AB     BC 
flow  through  the  galvanometer  when  aYv=(  f)' 

In  making  the  measurement,  a  resistance  box,  containing  a  large 
number  of  coils  of  wire  of  different  resistances,  is  used  (Fig.  221).  The 
resistances  corresponding  to  AB  and  AD  may  lie  made  equal,  or  may 
stand  to  each  other  in  a  ratio  of  i  :  10,  i  :  100,  etc.  Then,  the  un- 
known resistance  being  CD,  BC  is  adjusted  by  taking  plugs  out  of  the  box 


Fig.  220. — Wheat- 
stone's  Bridge. 


Fig.  221. — Diagram  of  Resistance  Box, 


till,  on  closing  the  current,  there  is  either  no  deflection,  or  the  deflection 
is  as  small  as  it  is  possible  to  make  it  with  the  given  arrangement. 

Galvanometers. — A  galvanometer  is  an  instrument  used  to  detect  a 
current,  to  determine  its  direction,  and  to  measure  its  intensity.  Since, 
by  Ohm's  law,  electromotive  force,  resistance,  and  current  strength 
are  connected  together,  any  one  of  them  may  be  measured  by  the  gal- 
vanometer. A  galvanometer  of  the  kind  ordinarily  used  in  physiology 
consists  essentially  of  a  small  magnet  suspended  in  the  axis  of  a  coil 


Fig.  222. — Sclicme  of  Wiedemann's  Galvanometer  (with  Telescope  Reading).  T, 
telescope;  S,  scale;  M,  mirror;  m,  ring  magnet  suspended  between  the  two  gal- 
vanometer coils  G,  the  distance  of  which  from  m  can  be  varied;  F,  fibre  suspend- 
ing mirror  and  magnet. 

of  wire,  and  free  to  rotate  under  the  influence  of  a  current  passing 
through  the  coil.  The  most  sensitive  instruments  possess  a  small 
mirror,  to  which  the  magnet  is  rigidly  attached.  A  ray  of  light  is 
allowed  to  fall  on  the  mirror,  from  which  it  is  reflected  on  to  a  scale; 
and  the  rotation  of  the  mirror  is  magnified  and  measured  by  the  ex- 
cursion of  the  spot  of  light  on  the  scale.  In  the  Thomson  galvanometers 
the  magnet  is  very  light — e.g.,  a  strip  or  two  of  magnetized  watch 
spring.  The  magnet  is  '  damped  ' — that  is.  its  tendency,  when  once 
displaced,  to  go  on  oscillating  about  its  new  position  of  equilibrium  is 


700        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


overcome  by  enclosing  it  in  a  narrow  air  space.  In  the  Wiedemann 
instrument  the  magnet  is  heavier  (Fig.  222).  It  swings  in  a  chamber 
with  copper  walls.  Every  movement  of  the  magnet  '  induces  '  cur- 
rents in  the  copper;  these  tend  to  oppose  the  movement,  and  so 
•damping'  is  obtained.  It  is  usual  to  read  the  deflections  of  the 
Wiedemann  galvanometer  by  means  of  a  telescope.  An  inverted  scale 
is  placed  over  the  telescope  at  a  distance  of,  say,  a  metre  from  the 
mirror;  an  upright  image  of  the  scale  is  formed  in  the  telescope  after 
reflection  from  the  mirror,  and  with  every  movement  of  the  latter  the 
scale  divisions  appear  to  move  correspondingly.  The  method  of  reading 
by  a  telescope  can  be  applied  to  any  mirror  galvanometer,  and  is  often 
extremely  convenient  in 
physiological  work. 
Sometimes  a  small  scale 
is  fastened  on  the  mirror 
itself,  and  observed  di« 
rectly  through  a  low- 
power  microscope. 


Fig.  223. — Astatic  Pair  of 
Magnets.  SN  and  NS  are 
the  magnets,  fixed  to  the 
vertical  piece  P.  Mis  a  mir- 
ror. The  arrow-heads  show 
the  direction  of  a  current 
which  deflects  both  mag- 
nets in  the  same  direction. 


Tig.  224. — Diagram  of  String  Galvanometer.  The 
string  or  fibre  CC  is  stretched  between  the  pules  of 
a  powerful  electromagnet.  When  a  current  passes 
down  the  string  it  is  deflected  is  the  direction  of  the 
large  arrow  a — i.e.,  at  right. angles  to  the  magnetic 
field  NS.  When  the  current  is  reversed,  the  string 
moves  in  the  opposite  direction.  The  movements 
of  the  string  can  be  observed  by  a  microscope,  A 
(objective  E),  passing  through  a  hole  bored  through 
the  centre  of  the  magnet  poles.  For  obtaining 
records  a  source  of  light  is  placed  at  B  and  concen- 
trated on  the  fibre  by  a  condenser,  F,  and  the  move- 
ments  of  the  shadow  are  recorded  by  photography 


In  many  galvanometers  the  magnets  attached  to  the  mirror  form  an 
'  astatic  '  pair  (Fig.  223).  Two  small  magnets  of  nearly  equal  strength 
are  connected  to  a  light  slip  of  horn  or  an  aluminium  wire,  with  their 
poles  in  opposite  directions.  The  earth's  magnetism  affects  them  op- 
positely, so  that  the  resultant  action  is  nearly  zero.  Either  one  or  both 
magnets  may  be  surrounded  by  the  galvanometer  coils.  If  both  are  so 
surrounded,  each  must  be  within  a  separate  coil,  and  the  current  must  pass 
in  opposite  directions  in  the  two  coils,  otherwise  they  would  neutralize 
each  other.  In  the  d'Arsonval  galvanometer  the  current  passes  through 
a  small  coil  of  fine  wire  suspended  in  the  field  of  a  strong  magnet.  Wlicn 
I  lie  current  passes  the  coil  is  deflected,  carrying  with  it  a  small  mirror 
a'  tachcd  to  the  suspending  filament.  A  great  advantage  of  this  galvano- 
meter in  many  situations  is  that  it  is  unaffected  by  neighbouring  currents. 


PRELIMINARY  DATA 


701 


The  string  galvanometer  of  Einthoven  has  pecuUar  merits  for  certain 
physiological  purposes.  It  consists  of  a  silvered  quartz-  or  glass-fibre 
stretched  in  a  very  strong  magnetic  field.     When  traversed  by  a  current 

the  fibre  is  deflected,  and  by  means 
of  a  beam  of  light  the  deflection  is 
greatly  magnified  (Fig.  224). 

A  rheocord  is  an  instrument  by 
HTcans  of  which  a  current  may  be 
divided,  and  a  definite  portion  of  it 
sent  through  a  tissue  (Fig.  225). 

A  compensator  is  simply  a  rheo- 
cord from  wliicli  a  brancli  of  a  current 
is  led  off,  to  balance  or  '  compen- 
sate '  any  electrical  difference  in  a 
tissue,  like  that  which  gives  rise  to 
the  current  of  rest  of  a  muscle,  for 
example  (Fig.  226). 

An  electrometer  is  an  instrument 
for  measuring  electromotive  force — 


Fig, 


225. — Diagram  of  Rheocord  (after 
Du  Bois-Reymond's  Model). 


Fig.  226. — Compeasator. 


Description  of  Fig.  225 :  I  to  VII  are  pieces  of  brass  connected  with  the  wires  atof 
in  such  a  way  that,  by  taking  out  any  of  the  brass  plugs  i  to  5,  a  greater  or  less 
resistance  may  be  interposed  between  the  binding-screws  A  and  B.  The  two  wires 
a  are  connected  by  a  slider  s,  filled  with  mercury  or  otherwise  making  contact  between 
the  wires.  The  current  from  the  battery  B  divides  at  A  and  B.  part  of  it  passing 
through  the  rheocord,  part  through  N,  the  nerve,  muscle,  or  other  conductor  which 
forms  the  alternative  circuit.  When  a  sufficient  resistance  R  is  interposed  in  the 
chief  circuit  to  make  the  total  strength  of  the  current  independent  of  changes  in  the 
resistance  of  the  rheocord,  the  strength  of  the  current  passing  through  N  will  vary 
inversely  as  the  resistance  of  the  rheocord.  When  all  the  plugs  are  in,  and  the  slider 
close  up  to  A,  there  is  practically  no  resistance  in  the  rheocord,  and  all  the  current 
passes  across  the  brass  pieces  and  plugs  to  B,  and  thence  back  to  the  battery.  As  s 
is  moved  father  away  from  A,  the  resistance  of  the  rheocoid  is  increased  more  and 
more,  and  theintensity  of  the  current  passing  through  N  becomes  greater  and  greater. 
The  scale  S  shows  the  length  of  wire  interposed  for  any  positioa  of  s,  a:id  this  gives  a 
rough  measure  of  the  fraction  of  the  current  passing  through  N.  When  plug  i  or  2  is 
taken  out,  a  resistance  equal  to  that  of  the  two  wires  a  is  interposed;  plug  3,  twice 
that  of  a  ;  plug  4,  five  times;  plug  5,  ten  times. 

Description  of  Fig.  226:  W  is  a  wire  stretched  alongside  a  scale  S.  A  battery  B  is 
connected  to  the  binding-screws  at  the  ends  of  the  wire.  A  pair  of  unpolarizable 
electrodes  are  connected,  one  with  a  slider  moving  on  a  wire,  the  other  through  a 
galvanometer  with  one  of  the  terminal  binding-screws.  In  the  figure  a  nerve  is 
shown  on  the  electrodes,  one  of  which  is  in  contact  with  an  uninjured  portion,  the 
other  with  an  injured  part.  The  slider  is  moved  until  the  twif,'  of  the  compensating 
oirrent  just  balances  the  demarcation  current  of  the  nerve  and  the  galvanometer 
shows  uo  deflection. 


702       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


that  is,  differences  of  electric  potential.  Lippmann's  capillary  elec- 
trometer has  been  much  employed  in  physiology.  A  convenient  form 
of  it  is  shown  in  Fig.  227.  A  simple  form,  suitable  for  students  work- 
ing in  a  class  where  a  considerable  number  of  copies  of  the  instrument 
is  needed,  can  be  conveniently  made  as  follows:  A  glass  tube  is  drawn 
out  to  a  capillary  at  one  end  and  filled  with  mercury.  The  tube  is 
inserted  into  a  small  glass  bottle,*  and  fastened  in  its  neck  by  a  cork 
or  a  plug  of  sealing-wax  which  does  not  quite  fill  the  opening,  so  that 
the  interior  of  the  bottle  is  still  in  communication  with  the  external  air. 
The  upper  end  of  the  tube  is  connected  by  a  short  piece  of  rubber  tubing 
with  a  glass  T-tube  as  in  Fig.  228.  The  bottle  is  partially  filled  with 
5  to  10  per  cent,  sulphuric  acid,  under  which  the  capillary  dips.  By 
means  of  a  small  reservoir  made  from  a  piece  of  glass  tubing  filled  with 
mercury,  and  connected  with  the  stem  of  the  T-tube,  a  little  mercury 
is  forced  through  the  capillary  so  as  to  expel  the  air  in  it.     When  the 


Fig.  227.  —  Capillary  Electro- 
meter (after  Frey),  as  arranged 
for  mounting  on  the  Microscope 
Stage.  The  electrometer  consists 
(i)  of  a  small  table  carrying  a 
parallel-sided  glass  vessel  contain- 
ing mercury  and  sulphuric  acid. 
(2)  The  capillary  tube,  which  can 
be  moved  in  two  directions  at 
right  angles  to  each  other,  and  so 
adjusted  in  the  field  of  the  micro- 
scope. (3)  A  pressure-vessel,  and 
a  manometer  connected  with  it 
for  measuring  the  pressure. 
(4)  Two  binding-screws  connected 
by  wires  to  the  mercury  in  the 
capillary  tube  and  in  the  parallel- 
sided  vessel.  The  binding-screws 
can  be  short-circuited  by  closing 
the  friction-key  shown  at  the 
right  side  of  the  figure,  thus  pre- 
venting  any  difference  of  elec- 
tromotive force  between  two 
points  connected  with  the  screws 
from  aSecting  the  electrometer. 


pressure  is  lowered  again,  sulphuric  acid  is  drawn  up,  and  now  lies  in 
the  capillary  in  contact  with  the  meniscus  of  the  mercury.  A  platinum 
wire  fused  through  the  tube,  or  simply  inserted  through  its  upper  end, 
dips  into  the  mercury.  Another,  passing  through  the  cork,  or,  better, 
fused  through  the  bottom  of  the  bottle,  makes  contact  with  the  sul- 
phuric acid  through  some  mercury.  The  bottle  is  fastened  on  the  stage 
of  a  microscope,  the  capillary  brought  into  focus,  and  the  meniscus 
adjusted  by  raising  or  lowering  the  reservoir.  When  the  platinum 
wires  are  connected  with  points  at  different  potential,  a  current  begins 

*  A  parallel-sided  bottle  is  best,  as  it  gives  the  clearest  image  of  the  menis- 
cus. But  it  is  easiest  to  make  a  cylindrical  bottle  from  a  piece  of  wide  glass 
tubing,  and  to  insert  a  platinum  wire  into  it  before  closing  it  at  the  bottom  in 
the  blow-pipe  flame.  The  tube  can  then  be  firmly  fastened  with  sealing-wax 
in  a  depression  in  a  piece  of  wood,  the  wire  being  brought  out  through  a  hole 
in  the  wood.  Once  the  instrument  is  arranged,  there  is  little  chance  of  the 
capillary  getting  broken,  and  there  is  very  little  evaporation  of  the  acid. 


PRELIMINARY  DATA 


703 


to  pass  through  the  instrument,  and  the  meniscus  of  the  mercurj-  in  the 
capillary  tube,  where  the  current  density  is  the  greatest,  becomes 
polarized  by  the  ions  separated  from  the  sulphuric  acid  at  the  surface 
of  contact  between  the  acid  and  the  mercury,  so  that  the  meniscus  is 
no  longer  in  e(iuiiil)rium  in  the  tube.  The  surface  tension  (p.  423)  is 
diminished  wlicu  tlic  direction  of  the  current  is  from  mercury  to  acid 
(mercury  at  a  higlicr  potential  than  acid),  and  is  no  longer  able  to  coun- 
terbalance the  hydrostatic  pressure  of  the  mercury.  The  meniscus  there- 
fore moves  down  in  the  tube.  With  the  opposite  direction  of  current 
(mercury  at  a  lower  potential  than  acid)  the  surface  tension  is  increased, 
and  the  meniscus  moves  up.  The  polarization  develops  itself  almost  in- 
stantaneously, and  thus  an  electromotive  force  is  at  once  established 
in  the  opposite  direction  to  that  between 
the  points  connected  with  the  electro- 
meter, and  equal  to  it  so  long  as  the 
external  electromotive  force  is  not 
sufficiently  great  to  cause  continuous 
electrolysis  of  the  acid — ^that  is,  so  long 

Fig.  228. — A  Simple  Capillary  Electro- 
meter. B,  bottle  containing  sulphuric 
acid;  Hg,  mercury;  E,  E',  platinum  wires. 
E  dips  into  the  mercury  in  the  vertical 
tube,  and  E'  is  fused  through  the  bottom 
of  B,  so  as  to  make  contact  with  the 
mercury  in  B,  the  other  end  of  it  passing 
out  through  a  small  hole  in  the  wooden 
platform  F,  on  which  B  rests.  F  is 
fastened  to  the  stage  of  the  microscope, 
S.  by  a  pin,  G,  passing  through  one  of 
the  clip-holes,  and  to  the  wooden  upright, 
D,  by  the  pin,  H.  D  fits  tightly  over  the 
microscope  stage,  but  can  be  moved 
laterally  a  little  so  as  to  bring  the  capil- 
lary into  the  middle  of  the  field.  /,  stem 
of  glass  T-tube  passing  through  a  hole  in 
D.  L,  rubber  tube  connecting  the  capil- 
lary point  with  the  vertical  portion  of  the 
T-tube.  A  is  a.  reservoir  containing 
mercury  connected  by  the  rubber  tube 
M  to  /.  A  can  be  raised  or  lowered  by 
sliding  it  in  the  clips  K.     C,  magnified 

portion    of    the    capillary  tube   showing         ' — "— = y- 

the  meniscus,  ,    t,  ^_^ 

-^^^'  "S 

as  it  is  below  about  2  volts.  The  external  current  is  therefore  at  once 
compensated,  and  after  the  first  moment  no  current  passes  through  the 
instrument,  which  is  accordingly  not  a  measurer  of  current,  but  of 
electromotive  force. 

Induced  Currents. — When  a  coil  of  wire  in  which  a  current  is  flowing 
is  brought  up  suddenly  to  another  coil,  a  momentary  current  is  developed 
in  the  stationary  coil  in  the  opposite  direction  to  that  in  the  moving 
coil.  Similarly,  if  instead  of  one  of  the  coils  being  moved  a  current  is 
sent  through  it,  while  the  other  coil  remains  at  rest  in  its  neighbour- 
hood, a  transient  oppositely-directed  current  is  set  up  in  the  latter. 
When  tlie  current  in  the  first  coil  is  broken,  a  current  in  the  same 
direction  is  induced  in  the  other  coil. 

Du  Bois-Reymond's  Sledge  Inductorium  (Fig.  229). — This  consists  of 
two  coils,  the  primar^"^  and  the  secondary,  the  former  having  a  com- 


704 


THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


parativel}'  small  number  of  turns  of  fairly  thick  copper  wire,  the  latter 
a  large  number  of  turns  of  thin  wire.  The  object  of  this  is  that  the 
resistance  of  the  primary,  which  is  connected  with  one  or  more  voltaic 
cells,  may  not  cut  down  the  current  too  much;  while  the  currents 
induced  in  the  secondary,  having  a  high  electromotive  force,  can  readily 
pass  through  a  high  resistance,  and  are  directly  proportional  in  intensity 
to  the  number  of  turns  of  the  wire. 

By  means  of  various  binding-screws  and  the  electro-magnetic  inter- 
rupter or  Neef's  hammer,  shown  in  the  figure  and  explained  below  it, 
the  current  can  be  made  once  in  the  primary  or  broken  once,  or  a  con- 
stant alternation  of  make  and  break  can  be  kept  up.  We  can  thus  get 
a  single  make  or  break  shock  in  the  secondary,  or  a  series  of  shocks, 
sometimes  called  an  interrupted  or  faradic  current.  Such  a  series  of 
stimuli  can  also  be  got  by  making  and  breaking  a  voltaic  current  at  any 
given  rate. 

A  '  self -induced  '  current  can  also  be  obtained  from  a  single  coil;  for 
instance,  from  the  primary  coil  alone  of  the  induction  apparatus.     The 


Fig.  229. — Du  Bois-Reymond's  Inductorium.  B,  primary,  B',  secondary,  coil, 
H,  guides  in  which  B'  slides,  with  scale;  D.  electro-magnet;  E,  vibrating  spring; 
i,  wire  connecting  wire  of  D  to  end  of  primary;  v,  screw  with  platinum  point, 
connected  with  other  end  of  primary ;  A,  A',  binding-screws,  to  which  are  attached 
the  wires  from  battery.  A'  is  connected  with  the  wire  of  the  electro-magnet  D; 
and  through  it  and  i  with  the  primary. 

reason  of  this  is,  that  when  a  current  begins  to  flow  through  any  turn 
of  a  coil  of  wire  it  induces  in  all  the  other  turns  a  current  in  the  opposite 
direction,  and,  when  it  ceases  to  flow,  a  current  in  the  same  direction 
as  itself.  The  former  current,  '  the  make  extra  shock,'  being  in  the 
opposite  direction  to  the  inducing  current,  is  retarded  in  its  develop- 
ment, and  reaches  its  maximum  more  slowly  than  '  the  break  extra 
shock.'  But,  as  we  shall  see,  the  suddenness  with  which  an  electrical 
change  is  brought  about  is  one  of  the  most  important  factors  in  elec- 
trical stimulation,  and  tlaerefore  the  break  extra  shock  is  a  much  more 
powerful  stimulus  than  the  make.  Owing  to  these  self-induced  currents, 
the  stimulating  power  of  a  voltaic  stream  may  be  much  increased  by 
putting  into  the  circuit  a  coil  of  wire  of  not  too  great  resistance. 

The  self-induction  of  the  primary  also  affects  the  stimulating  power 
of  the  currents  induced  in  the  secondary;  the  shock  induced  in  the 
secondary  by  break  of  the  primary  current  is  a  stronger  stimulus  than 
that  caused  at  make  of  the  primary.  The  reason  is  that  with  a  given 
distance  of  primary  and  secondary,  and  a  given  intensity  of  the  voltaic 


PRELIMINARY  b.lTA  705 

current  in  the  primary,  the  abruptness  with  which  the  induced  current 
in  the  sccondi',ry  is  developed  depends  upon  the  rapidity  with  which  the 
primary  current  readies  its  maximum  at  closing,  or  its  minimum  (zero) 
at  opening.  Now,  the  make  extra  current  retards  the  development  of 
the  primary  current,  while  in  the  opened  circuit  of  the  primary  coil  the 
current  intensity  falls  at  once  to  zero. 

The  inequality  between  the  make  and  break  shocks  of  the  secondary 
coil  can  be  greatly  reduced  by  means  of  Helmholtz's  wire.  Connect  one 
pole  of  the  battery  with  v  (Fig.  229).  and  the  other  with  A'.  Join  A 
and  A'  by  a  short,  thick  wire.  With  this  arrangement  tlie  primar>-  cir- 
cuit is  never  opened,  but  the  current  is  alternately  allowed  to  flow 
through  the  primary,  and  short-circuited  when  the  spring  touches  v. 
The  '  make  '  now  corresponds  to  the  sudden  increase  of  intensity  of 
the  current  in  the  primary  when  the  short-circuit  is  removed,  and  the 
'break'  to  its  sudden  decrease  when  the  short-circuit  is  established. 
In  both  cases  self-induced  currents  are  developed,  and  therefore  both 
shocks  are  weakened.  But  the  opening  stimulus  is  now  slightly  the 
weaker  of  the  two,  because  the  opening  extra  shock  has  to  pass  through 
a  smaller  resistance  (the  short-circuit)  than  the  closing  extra  shock 
(which  passes  by  the  battery),  and  therefore  opposes  the  decline  of 
current  intensity  on  short-circuiting  more  than  the  closing  shock 
opposes  the  increase  of 
current  intensity  on  long- 
circuiting  through  the 
primary. 

By  means  of  wires  con- 
nected with  the  terminals 
of    the    secondary     coil, 
and  leading  to  electrodes, 
a    nerve   or   muscle   may     p|g     230.  — Unpolarizable   Electrodes.      A,    hook- 
be  stimulated.    It  is  usual         shaped;   B,    U-tubes;    C,   straight;    D,   clay  in 
to  connect    the   wires   to         contact  with    tissue;   S,  saturated  zinc  sulphate 
a     short-circuiting     key         solution;  Z,  amalgamated  zinc  wire. 
(Fig.    232),    by    opening 

which  the  induced  current  is  thrown  into  the  tissue  to  be  stimu- 
lated. For  some  purposes  the  electrodes  may  be  of  platinum; 
but  all  metals  in  contact  with  moist  tissues  become  polarized  when 
currents  pass  through  them — that  is,  have  decomposition  products  of 
the  electrolysis  of  the  tissues  deposited  on  them.  And  as  any  slight 
chemical  difference,  or  even  perhaps  a  difference  of  physical  state,  be- 
tween the  two  electrodes  will  cause  them  and  the  tissues  to  form  a 
batterj'^  evolving  a  continuous  current,  it  is  often  desirable  to  use  un- 
polarizable electrodes. 

Unpolarizable  Electrodes. — Some  convenient  forms  of  these  arc 
represented  in  Fig.  230.  A  piece  of  amalgamated  zinc  wire  dips  into 
saturated  zinc  sulphate  solution  contained  in  tlie  upper  part  of  a  glass 
tube.  The  lower  end  of  the  tube  may  be  straight,  but  drawn  out  so 
as  to  terminate  in  a  not  very  large  opening,  or  it  may  be  bent  into  a 
hook,  in  the  bend  of  which  a  hole  is  made.  Before  the  tube  is  filled 
with  the  zinc  sulphate  solution,  the  lower  pait  of  it  is  plugged  with 
china  clay  made  up  with  physiological  salt  solution.  The  clay  just 
projects  through  the  opening,  and  thus  comes  in  contact  with  the 
tissue.  When  these  electrodes  are  properly  set  up,  there  is  very  little 
polarization  for  several  hours,  but  for  long  experiments,  U-shaped 
tubes,  filled  with  saturated  zinc  sulphate  solution,  are  better.  The 
amalgamated  zinc  dips  into  one  limb,  and  a  small  glass  tube  filled  with 
clay,  on  which  the  tissue  is  laid,  into  the  other. 

45 


7o6        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


Pohl's  Commutator  or  Reverser  (Fig.  231)  consists  of  a  block  of  paraf- 
fin or  wood  with  six  mercury  cups,  each  in  connection  with  a  binding- 
screw  (not  sliown  in  the  figure).  Cups  i  and  6  and  2  and  5  are  connected 
by  copper  wires,  which  cross  each  other  without  touching.  The  bridge 
consists  of  a  glass  or  vulcanite  cross-piece  a,  to  which  are  attached  two 
wires  bent  into  semicircles,  each  connected  with  a  straight  wire  dip- 
ping into  the  cups  3  and  4  respectively.  With  the  bridge  in  the  posi- 
tion shown  in  the  figure,  a  current  coming  in  at  4  would  pass  out  by 
the  wire  connected  with  i,  and  back  again  by  that  connected  with  2,  in 
the  direction  shown  by  the  arrows.  When  the  bridge  is  rocked  to  the 
other  side  so  that  the  bent  wires  dip  into  5  and  6,  the  direction  of  the 
current  is  reversed.  The  cross-wires  may  be  taken  out  altogether,  and 
the  commutator  used  to  send  a  current  at  will  through  either  of  two 
circuits,  one  connected  with  i  and  2,  and  the  other  with  5  and  6. 

Du  Bois -Reymond's  Short- 
circuiting  Key. — A  cheap  and 
convenient  form  is  shown  in 
Fig.  232. 

Time  -  Markers  —  Electric  Sig- 
nal.— It  is  of  importance  to  know 
the  time  relations  of  many 
physiological  phenomena  which 
are    graphically    recorded  ;     for 


+    ^ 
Fig.  231. —  Pohl's  Commutator. 


Fig.  2:2.— Short-Circuiting  Key. 


example,  the  contraction  of  a  skeletal  muscle  or  the  beat  of  a  heart. 
For  this  purpose  a  tracing  showing  the  speed  of  the  trav<^ling  sur- 
face in  a  given  time  is  often  taken  simultaneously  with  the  record 
of  the  movement  under  investigation.  For  a  slowly-moving  surface 
it  is  sufficient  to  mark  intervals  of  one  or  two  seconds,  and  this  is 
very  readily  done  by  connecting  an  electro-magnetic  marker  (such  as 
the  electric  signal  of  Dcprez)  with  a  circuit  which  is  closed  and  broken 
by  the  seconds  pendulum  of  an  ordinary  clock  (Fig.  233)  or  a  metronome 
(Fig.  88,  p.  193).  Special  clocks  have  also  been  constructed  which 
permit  of  the  time  intervals  being  varied.  For  shorter  intervals  a 
tuning-fork  is  used,  which  makes  and  breaks  a  circuit  including  an 
electromagnetic  marker,  or  writes  on  the  drum  directly  by  means  of 
a  writing-point  attached  to  one  of  the  prongs. 

Amoeboid  movement  (p.  16)  is  the  most  primitive,  the  least 
elaborated  form  of  contraction.  The  maximum  velocity  of  the 
movement  has  been  reckoned  at  o-oo8  millimetre  a  second.  Stimu- 
lation with  the  constant  current  or  induction  shocks  causes  the 
whole   of   the    pseudopodia   to   be   drawn   in.      This   illustrates   a 


CILIA 


707 


universal  property  of  protoplasm,  excitability,  or  the  power  of  re- 
sponding to  certain  inlluences,  or  stimuli,  by  manifestations  of  the 
peculiar  kind  which  we  distinguish  as  vital  or  physiological.  Many 
unicellular  organisms  and  the  chief  varieties  of  the  white  blood- 
corpuscles  possess  the  power  of  amoeboid  movement ;  and  we  have 
already  dwelt  upon  some  of  the  important  functions  fulfilled  by 
such  movement  in  the  higher  animals  and  in  man.  A  great  dis- 
tinction between  this  kind  of  contraction  and  that  of  a  muscular 
fibre  is  that  it  takes  place  in  any  direction. 

Cilia. — Cilia  possess  a  higher  and  more  specialized  grade  of 
contractihty.  They  are  very  widely  distributed  in  the  animal 
kingdom;  and  analogous  structures  are  also  found  in  many  low 
plants,  such  as  the  motile  bacteria. 

In  the  human  subject  ciliated 
epithelium  usually  consists  of 
several  layers  of  cells,  the  most 
superficial  of  which  are  pear-shaped, 
the  broad  end  being  next  the  sur- 
face, and  covered  with  extremely 
fine  processes,  or  cilia,  about  8  /* 
in  length,  which  are  planted  on 
a  clear  band.  It  lines  the  respi- 
ratory passages,  the  middle  ear  and 
Eustachian  tube,  the  Fallopian  tubes, 
the  uterus  above  the  middle  of  the 
cervix,  the  epididymis,  where  the 
cilia  are  extremely  long,  and  the 
central  cavity  of  the  brain  and 
spinal  cord. 

Ciliary  motion  can  be  readily 
studied  by  placing  a  scraping  from 
the    palate   of   a   frog   or   a    small 


Fig-  233. — Time-Marker.  Arrange- 
ment for  marking  2 -second  inter- 
vals. D,  seconds  pendulum,  with 
platinum  point  E  soldered  on;  A, 
mercury  trough,  into  which  E  dips 
at  end  of  its  swing;  B,  Daniellcell; 
C,  electro  -  magnet  which  draws 
down  writing  -  lever  F  when  the 
current  is  closed  bvE  dipping  into 
A;  G,  spring  (or  piece  of  india- 
rubber),  which  raises  F  as  soon  as 
currant  is  broken. 


portion  of  the  gill  of  a  fresh-water 
mussel  under  the  microscope  in  a  drop  of  physiological  salt  solution. 
The  motion  of  the  cilia  is  at  first  so  rapid  that  it  is  impossible  to 
make  out  much,  except  that  a  stream  of  liquid,  recognized  by  the 
solid  particles  in  it,  is  seen  to  be  driven  by  them  in  a  constant  direc- 
tion along  the  ciliated  edge.  When  the  motion  has  become  less 
quick,  which  it  soon  does  if  the  tissue  is  deprived  of  oxygen,  it  is 
seen  to  consist  in  a  swift  bending  of  the  cilia  in  the  direction  of  the 
stream,  followed  by  a  slower  recoil  to  the  original  position,  which 
is  not  at  right  angles  to  the  surface,  but  sloping  streamwards.  All 
the  cilia  on  a  tract  of  cells  do  not  move  at  the  same  time ;  the  motion 
spreads  from  cell  to  cell  in  a  regular  wave.  The  energy  of  cihary 
motion  may  be  considerable,  although  far  inferior  to  that  of  mus- 
cular contraction.     The  work  wliich  ciUa  are  capable  of  performing 


7o8       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 


can  be  calculated  by  removing  the  membrane,  fixing  it  on  a  plate 
of  glass,  cilia  outwards,  putting  weights  on  the  glass  plate,  and 
allowing  the  cilia,  like  an  immense  number  of  feet,  to  carry  it  up 
an  inclined  plane.  Bowditch  found  in  this  way  that  the  cilia  on 
a  square  centimetre  of  mucous  membrane  did  nearly  7  gramme- 
millimetres  of  work  per  minute  (equal  to  the  raising  of  7  grammes  to 
a  height  of  a  millimetre). 

Since  the  cilia  in  the  respiratory  tract  all  lash  upwards,  they 
must  play  an  important  part  in  carrying  up  foreign  particles  taken 

in  with  the  air,  and  the  mucus  in  which 
they  are  entangled,  as  well  as  patho- 
logical products.  Engelmann  found 
that  the  energy  of  ciliary  motion  in- 
creases as  the  temperature  is  raised, 
up   to   about   40°  C.,    after   which    it 


Fig.  234.— Ciliated  Cell  (M. 
Heidenhain).  From  a 
'  liver  duct '  of  the  garden 
snail  X  2,500. 


Fig.  235.— Ciliated  Cell  (Schneider). 
From  a  flatworm  (P/a«octfm/oZtMf»). 
I,  space  between  two  adjoining 
ciliated  cells;  2,  basal  bodies;  4, 
inner  granule;  5,  'cilia  roots'; 
6,  boundary  layer. 


diminishes  quickly.  Over-heating  causes  cilia  to  come  to  rest,  but 
if  the  temperature  has  not  been  too  high,  and  has  not  acted  too 
long,  they  recover  on  cooling,  thus  exhibiting  the  phenomena  of 
heat  standstill  which  we  have  already  studied  in  the  heart. 

It  is  not  well  understood  in  what  way  the  contraction  of  the  cilia 
depends  upon  their  connection  with  the  body  of  the  ciliated  cell.  Very 
few  cases  occur  in  which  cilia  have  the  power  of  independent  motion 
wlien  severed  from  the  cell-body.  It  has  been  observed  in  certain  low 
forms  of  animals  that  cilia  which  have  been  broken  off  from  the  cell 
are  still  able  to  contract  when  a  small  portion  of  the  substance  of  the 


PHYSICAL  PROPERTIES  OF  MUSCLE  709 

cell-body  at  the  point  where  the  cilium  is  attached  to  the  cell,  the 
so-called  basal  piece,  or  basal  body  (Fig.  235),  has  come  off  along  with 
them.  In  other  forms  isolated  cilia  can  contract  in  the  absence  of 
anything  corresponding  to  the  basal  piece.  It  cannot,  therefore,  be 
said  that  continuity  with  the  basal  piece  is  absolutely  necessary.  Nor 
is  it  known  what  significance  for  the  ciliary  movements  is  possessed 
by  the  long  fibrilhe,  called  the  '  roots  of  the  cilia,'  which  in  some  animals 
run  down  through  the  cell  from  the  basal  bodies  (Figs.  234,  235).  In 
some  worms  and  molluscs  ciliated  cells  are  supplied  with  nerve-fibres, 
but  this  has  not  been  demonstrated  for  the  higher  animals. 

Section  II. — Physical  Properties  and  Stimulation  of  Muscle, 

Since  most  of  our  knowledge  of  the  general  physiology  of  muscle 
has  been  gained  from  striped  muscle,  in  what  follows  we  always 
refer  to  ordinary  skeletal  muscle,  unless  it  is  otherwise  stated. 
The  sartorius  and  the  gastrocnemius  are  the  classical  objects  for 
experiments  on  striated  muscle.  For  smooth  muscle  the  adductor 
muscle  of  Anodon,  the  fresh-water  mussel,  a  ring  cut  from  the  middle 
portion  of  the  frog's  stomach,  the  rabbit's  ureter  and  uterus,  and 
the  cat's  bladder,  have  been  most  used. 

Physical  Properties  of  Muscle — Elasticity. — All  bodies  may  have  their 
shape  or  volume  altered  by  the  application  of  force.  Some  require  a 
large  force,  others  a  small  force,  to  produce  a  sensible  amount  of  dis- 
tortion. The  elasticity  of  a  body  is  the  property  in  virtue  of  which  it 
tends  to  recover  its  original  form  or  bulk  when  these  have  been  altered. 
Liquids  and  gases  have  only  elasticity  of  volume;  solids  have  also 
elasticity  of  form.  Most  solids  recover  perfectly,  or  almost  perfecth', 
from  a  slight  deformation.  The  limits  of  distortion  within  which  tli'is 
occurs  are  called  the  limits  of  elasticity,  and  they  vary  greatly  for 
different  substances.  Living  muscle  has  very  wide  limits  of  elasticity; 
it  may  be  deformed — stretched,  for  example — to  a  very  considerable 
extent,  and  yet  recover  its  original  length  .when  the  stretching  force 
ceases  to  act. 

The  extensibility  of  a  body  is  measured  by  the  ratio  of  the  increase 

of  length,  produced  by  unit  stretching  force  per  unit  of  area  of  the 

cross-section,  to  the  original  length  of  a  uniform  rod  of  the  substance. 

Is 
If  e  is  the  extensibility,  6=  y^.  where  I  is  the  increase  of  length, 

L  the  original  length,  s  the  cross-section,  and  F  the  stretching  force. 
Suppose  we  wish  to  compare  tlie  extensibility  of  two  substances. 
Let  A  and  B  be  strips  or  rods  of  the  substances,  the  length  of  A  being 
500  mm.,  that  of  B  1,000  mm.;  the  cross-section  of  A,  100  sq.  mm.,  of 
B,  200  sq.  mm.     Let  the  elongation  produced  by  a  weight  of  i   kilo 

be  10  mm.  in  each,  then  the  extensibility  of  A  is    "^    ""=  2 ;  and  that 

500  X  I 
,  ^   .      10x200  ^,    a    . 

of  B  IS   J "  Q~~^  =  2 ;  that  IS,   the  substances  are  equally  extensible. 

Young's  modulus  of  elasticity,  or  the  coefficient  of  elasticity,  is  the 
quotient  of  the  deforming  force  acting  on  unit  area  of  the  given  body 
by  the  deformation  produced  (within  the  limits  of  elasticity).     In  the 

F     /  IF 

above  example  it  is      -^j-.  that  is,  -j   .  the  reciprocal  of  the  extensi- 


710         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

bility  e.  For  steel  the  coefficient  of  elasticity  is  very  large,  for  muscle 
small.  Or,  as  we  may  otherwise  express  it,  living  muscle  within  its 
limits  of  elasticity  is  very  extensible;  a  small  force  per  unit  area  of 
cross-section  of  a  prism  of  it  will  produce  a  comparatively  great  elonga- 
tion. The  extensibilitv.  however,  diminishes  continually  with  the 
elongation,  so  that  equal  increments  of  stretching  force  produce  alwaj's 
less  and  less  extension.  If,  for  instance,  tJie  sartorius  or  semi-mem- 
branosus  of  a  frog  be  connected  with  a  lever  writing  on  a  blackened 
surface,  and  weights  increasing  by  equal  amounts  be  successively 
attached  to  it,  the  recording  surface  being  allowed  to  move  the  same 
distance  after  the  addition  of  each  weight,  a  series  of  vertical  lines, 
representing  the  amount  of  each  elongation,  will  be  traced.  When  the 
lower  ends  of  all  the  vertical  lines  are  joined,  a  smooth  curve  with  the 
concavity  upwards  is  obtained  (Fig.  236).  This  is  a  property  common 
to  living  and  dead  muscle  and  to  other  animal  structures,  such  as 
arteries.  Marey's  method,  in  which  the  weight  is  continuously  in- 
creased from  zero  and  then  continuously  decreased  to  zero  again  by 
the  flow  of  mercury  into  and  out  of  a  vessel  attached  to  the  muscle, 
gives  directly  the  curve  of  extensibility. 

The  elongation  of  a  steel  rod  or  other 
inorganic    solid     is     proportional     within 
limits  to  the  extending  force  per  unit  of 
cross-section ;  and  a  curve  plotted  with  the 
weights  for  abscissae  and  the  amounts  of 
elongation  f or  ordinates  would  be  a  straight 
line.     But  this  is  not  a  fundamental  dis- 
tinction between  animal  tissues,  and  the 
materials  of  unorganized  nature,  as  some 
writers  seem  to  suppose.     For  when  the 
slow    after-elongation   which    follows  the 
first  rapid  increase  in  length  in  the  loaded, 
Fig.    236. — Curves   of  Extensi-    excised  muscle  is  waited  for,  the  curve  of 
bility.    M,  of  muscle;  S,  of  on    extensibility    comes    out    a    straight    line 
ordinary  inorganic  solid.  (Wundt),  and  within  limits  this  is  also  the 

case  for  human  muscles  in  the  intact  body. 
And  although  a  steel  rod  much  more  quickly  reaches  its  maximum 
elongation  for  a  given  weight  when  loaded,  and  its  original  length  when 
the  weight  is  removed,  than  does  a  muscle,  time  is  required  in  both  cases, 
and  the  difference  is  one  of  degree  rather  than  of  kind.  When  muscle 
(striated  or  smooth)  is  not  stretched  beyond  the  limit  of  physiological 
relaxation,  the  amount  of  stretching  is  proportional  to  the  weight,  and 
the  same  is  true  of  all  the  simple  tissues  of  the  body  (Haycraft). 

Dead  muscle  is  less  extensible  than  living,  and  its  limits  of  elasticity 
are  much  narrower.  In  the  state  of  contraction  the  extensibility  is 
increased  in  excised  frog's  muscle.  When  fatigue  comes  on  after  many 
excitations,  the  after-elongation  becomes  more  pronounced,  but  the 
return  after  unloading  is  very  incomplete.  Donders  and  Van  Mans- 
veldt  have  found  that  contraction  causes  little  difference  in  the  muscles 
of  a  living  man,  although  fatigue  increases  the  extensibility. 

The  great  extensibility  and  elasticity  of  muscle  must  play  a  con- 
siderable part  in  determining  the  calibre  of  the  vessels,  and  in  lessening 
the  shocks  and  strains  which  the  heart  and  the  vascular  system  in 
general  are  called  upon  to  bear,  and  must  contribute  much  to  the 
smoothness  with  which  the  movements  of  the  skeleton  are  carried  out, 
and  immensely  reduce  the  risk  of  injury  to  the  bones  as  well  as  to  the 
muscles  themselves,  the  tendons  and  the  other  soft  tissues.  And  not 
only  is  smoothness  gained,   but  economy  also ;   for  a  portion  of  the 


STIMULATION  OF  MUSCLE  yn 

energy  of  a  sudden  contraction,  which,  if  the  muscles  were  less  ex- 
tensible and  elastic,  might  be  wasted  as  heat  in  the  jarring  of  bone 
against  bone  at  the  joints,  is  stored  up  in  the  stretched  muscle  and 
again  given  out  in  its  elastic  recoil.  The  skeletal  muscles,  too,  are 
even  at  rest  kept  sliglitly  on  the  stretch,  braced  up,  as  it  were,  and 
ready  to  act  at  a  moment's  notice  without  taking  in  slack.  This  is 
shown  by  the  fact  that  a  transverse  wound  in  a  muscle  '  gapes,'  the 
fibres  being  retracted,  in  virtue  of  their  elasticity,  towarcs  the  fixed 
points  of  origin  and  insertion.  Smooth  muscle,  as  we  meet  it  in  the 
hollow  viscera,  is  highly  tlistensiblc  and  clastic,  as  is  suited  to  organs 
whose  capacity  is  continually  varying  within  wide  limits  (Fig.  237). 

In  the  further  study  of  muscle  it  is  necessary  first  of  all  to  consider 
the  means  we  have  of  calling  forth  a  contraction — in  other  words,  the 
various  kinds  of  stimuli. 

Stimulation  of  Muscle. — A  muscle  may  be  excited  or  stimulated 
either  directly  or  through  its  motor  nerve.  It  is  usual  to  classify 
stimuli  as  electrical,  mechanical,  chemical,  or  thermal.  Electrical 
stimuli  are  by  far  the  most  commonly  employed,  and  will  be  dis- 
cussed in  detail.     A  prick,  a  cut,  or  a  blow  are  examples  of  mechani- 


Fig.  237. — Extensibility  of  Smooth  Muscle  (Griitzner).  The  upper  group  of  four 
cells  (i  to  4)  is  from  a  hallow  organ,  whose  walls  are  contracted,  and  its  lumen 
almost  abolished;  the  under  group  represents  the  same  fibres  when  the  organ  is 
full.  The  fibres  are  longer  and  somewhat  darker.  They  are  also  displaced 
somewhat  along  each  other. 

cal  stimuli.  The  action  of  a  fairly  strong  solution  of  common  salt 
or  of  a  dilute  solution  of  a  mineral  acid  is  usually  described  as 
chemical  stimulation.  But  in  considering  the  excitation  of  nerve 
(p.  757)  we  shall  see  that  physical  changes  arc  often  mixed  up  with 
so-called  clioiriical  stimulation.  The  contraction  caused  is  not  a 
single  brief  '.Nitch,  as  is  the  case  with  a  not  too  severe  mechanical 
excitation,  bal  a  sustained  contraction  or  a  tetanus.  Sudden  cooling 
or  heating  acts  as  a  stimulus  for  muscle,  but  thermal  stimulation  is 
somewhat  uncertain.  It  is  not  quite  settled  whether  the  contrac- 
tion which  can  be  obtained  from  a  muscle  when  it  is  subjected  to 
brief  local  heating — to  a  '  thermic  shock,'  as  some  writers  prefer 
to  say  {e.g.,  by  the  momentary  glow  of  a  platinum  wire  below  but 
not  touching  it) — is  an  ordinary  muscular  contraction,  or  a  physical, 
although  transient,  contracture  analogous  to  that  caused  by  certain 
drugs  (Waller).  Smooth,  like  striped,  muscle  is  susceptible  to 
electrical,  mechanical,  thermal,  and  chemical  stimulation.  In 
addition,  in  certain  situations  it  can  be  excited  by  light  (photic 
stimulation),  as  in  the  case  of  the  excised  iris  of  fish  and  amphibia. 


712         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

In  all  artificial  stimulation  there  is  an  element  of  sudden  or  abrupt 
change,  of  shock,  in  other  words;  but  we  cannot  tell  in  what  the 
'  natural  '  or  '  physiological  '  stimulus  to  muscular  contraction  in 
the  intact  body  really  consists,  nor  how  it  differs  from  artificial 
stimuli.  All  we  know  is  that  there  must  be  a  ^\^de  difference,  and 
that  our  methods  of  excitation  must  be  very  crude  and  inexact 
imitations  of  the  natural  process. 

Direct  Excitability  of  Muscle. — The  famous  controversy  on  the 
existence  of  independent  '  muscular  irritability  '  has  long  been 
forgotten,  and  has  no  further  interest  except  for  the  antiquaries  of 
science,  if  such  exist.  The  direct  excitability  of  muscle  in  the  modern 
sense  is  not  quite  the  same  as  the  '  muscular  irritability,'  the  dis- 
cussion of  which  occupied  Haller  and  his  contemporaries.  What 
the  modern  physiologists  have  been  called  upon  to  decide  is  whether 
muscular  fibres  can  be  caused  to  contract  except  by  an  excitation 
that  reaches  them  through  their  nerves.  In  this  sense  there  can 
exist  no  doubt  that  muscle  is  directly  excitable,  and  some  of  the 
proofs  are  as  follows: 

(i)  The  ends  of  the  frog's  sartorius  contain  no  nerves,  yet  they 
respond  to  direct  stimulation.  (2)  Certain  chemical  stimuli — 
ammonia,  for  instance — excite  muscle  but  not  nerve.  (3)  When 
the  motor  nerves  of  a  limb  are  cut  they  degenerate,  and  after  a 
certain  time  stimulation  of  the  nerve-trunk  causes  no  muscular 
contraction,  while  the  muscles,  although  atrophied,  can  be  made 
to  contract  by  direct  stimulation.  (4)  Finally,  there  is  the  cele- 
brated curara  experiment  of  Claude  Bernard,  which  is  described  in 
a  somewhat  modified  form  in  the  Practical  Exercises,  p.  784.  A- 
ligature  is  tied  firmly  round  one  thigh  of  a  frog,  omitting  the  sciatic 
nerve;  then  curara  is  injected,  and  in  a  short  time  the  skeletal 
muscles  are  paralyzed.  That  the  seat  of  the  paralysis  is  not  the 
contractile  substance  of  the  muscles  itself  is  shown  by  their  vigorous 
response  to  direct  stimulation.  The  '  block  '  is  not  in  the  nerve- 
trunk,  nor  above  it  in  the  central  nervous  system,  for  the  ligated 
leg  is  often  drawn  up — that  is,  its  muscles  are  contracted — although 
the  poison  has  circulated  freely  in  the  sacral  plexus  and  the  spinal 
cord.  Further,  if  the  nerve  of  the  ligated  leg  be  prepared  as  high 
up  above  the  ligature  as  possible,  where  the  curara  must  undoubtedly 
have  reached  it  (just  above  the  ligature  the  nerve  has  been  isolated 
and  the  circulation  in  it  more  or  less  interrupted),  stimulation 
of  it  will  cause  contraction  of  the  muscles  of  the  limb;  while  excita- 
tion of  the  other  sciatic  is  ineffective. 

It  can  be  also  shown,  by  means  of  the  negative  variation  or 
current  of  action  (p.  797),  that  a  nerve-trunk  on  which  curara  has 
acted  remains  excitable,  and  capable  of  conducting  the  nerve- 
impulse.  The  conclusion,  therefore,  is  that  the  curara  paralyzes 
neither  nerve-fibre  nor  the  contractile  substance  of  the  muscular 


STIMULATION  OF  MUSCLE 


713 


fibre,  but  some  link  between  the  two.  If  the  assumption  be  made 
that  the  efferent  meduUated  nerve-fibres  within  the  muscle,  since 
they  are  anatomically  similar -to  those  in  the  nerve-trunk  till  near 
their  terminations,  are  similarly  affected  by  curara — and  it  is  a 
justifiable  assumption — the  seat  of  the  curara  paralysis  must  either 
be  the  nerve-ending  or  some  mechanism,  physiological  if  not 
anatomical,  interposed  between  the  nerve-ending  and  the  con- 
tractile substance.  Now,  Langley  has  shown  that  the  contractions 
caused  by  the  local  application  of  dilute  nicotine  solution  to  points 
of  the  skeletal  muscles  of  the  frog,  both  in  normal  muscles  and  in 
muscles  whose  motor  nerves  and  nerve-endings  have  degenerated 
after  section  of  the  nerves,  are  prevented  by  curara       He  there- 


Fig.  238. — Frog's  Motor  Nerve-Ending  (Wilson).  A,  B,  C,  three  musiie-fibres.  The 
meduUated  ucrve  a  loses  its  medullary  sheath  and  breaks  up  on  B  at  i.  It  gives 
oS  at  2  a  large  non-meduUated  branch,  which  also  breaks  up  on  B.  The  nerve- 
endings  send  ultraterminal  fibrilla-  to  A,  B,  and  C,  some  of  which  were  seen  to 
end  in  suall  knobs.  A  separate  non-medullated  nerve,  «,  is  shown,  which  forms 
a  small  plexus  on  B,  one  filjre  of  which  penetrates  to  a  lower  plane  than  the  other, 
and  ends  by  forming  a  knob  under  the  sarcolemma. 

fore  concludes  that,  since  nicotine  produces  its  effects  by  a 
direct  action  on  muscle,  and  not  by  aji  action  on  nerve-endings 
or  on  any  special  structure  (such  as  the  protoplasmic  mass  or  '  sole  ' 
at  the  nerve-ending  in  many  animals)  interposed  between  the  nerve 
and  the  muscle,  no  such  special  structure  existing  in  the  frog 
(Fig.  238),  curara  must  also  act  directly  on  the  muscle.  But 
obviously  curara  docs  not  paralyze  the  general  contractile  substance 
of  the  muscle,  else  the  curarized  muscle  would  not  contract  on  direct 
stimulation.  Langley  accordingly  assumes  that,  in  addition  to  the 
contractile  or  '  general '  substance,  '  receptive  '  substances  exist 
in  the  fibre,  through  which  the  excitation  is  transferred  to  the  con- 
tractile substance  when  the  motor  nerve  is  stinuilated.  He  pictures 
these  receptive  substances  as  '  side-chains  '  of  the  contractile  mole- 
cule, in  accordance  with   Ehrhch's  theory  of   immunity   (p.   31), 


714        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

and  distinguishes  those  in  the  neighbourhood  of  the  nerve-ending 
from  those  present  throughout  the  muscle  fibre.  Both  the  slow 
local  tonic  contraction  and  the  quick,  brief  conducted  contractions 
or  twitches  set  up  in  a  muscle  fibre  by  nicotine,  but  especially  the 
latter,  are  much  more  easily  ehcited  in  that  part  of  it  which  Ues 
under  the  nerve-ending  than  elsewhere.  Indeed,  the  position  of 
the  nerve-endings  in  the  superficial  fibres  of  a  muscle  can  be  ascer- 
tained by  observing  the  points  which  respond  most  readily  to  nico- 
tine. Nicotine  and  curara,  etc.,  are  supposed  to  combine  with  the 
receptive  substance,  which  is  then  in  both  cases  rendered  incapable 
of  being  affected  by  nerve  impulses.  In  the  case  of  nicotine  an 
additional  action  results  from  the  combination  with  the  receptive 
substance — viz.,  the  change  in  the  contractile  substance  which  leads 
to  contraction.  Curara  paralyzes  the  transmission  of  the  excitation 
from  the  motor  nerves  to  smooth   muscle — ^the  muscles  of  the 


Fig.  239. — Tonic  Contraction  of  Muscle  during  Passage  of  Constant  Current.  Two 
sartorius  muscles  of  frog  connected  by  pelvic  attachments.  Current  from  12 
small  Daniell  cells  in  series  passed  through  their  whole  length.  Current  closed 
at  m,  opened  at  b.     Time  trace,  two-second  intervals. 

bronchi,  for  instance — with  much  greater  difficulty  than  to  ordinary 
skeletal  muscle,  and  the  same  is  true  of  the  inhibitory  nerves  of 
the  heart. 

The  action  of  curara  gives  us  the  means  of  stimulating  muscle 
directly;  when  electrical  currents  are  sent  through  a  non-curarized 
muscle,  there  is  in  general  a  mixture  of  direct  and  indirect  stimula- 
tion, for  the  nerve-fibres  within  the  muscle  are  also  excited.  Induced 
currents  stimulate  nerve  more  readily  than  muscle.  Voltaic  currents 
may  excite  a  muscle  whose  nerves  have  degenerated,  while  induced 
currents  are  entirely  without  effect. 

For  direct  stimulation,  a  curarized  frog's  sartorius  or  semi-mem- 
branosus  is  generally  used  on  account  of  their  long  parallel  fibres.  For 
indirect  excitation,  a  muscle-nerve  preparation,  composed  of  a  frog's 
gastrocnemius  with  the  sciatic  nerve  attached  to  it,  is  commonly  em- 
ployed, as  it  is  easy  to  isolate  the  muscle  without  hurting  its  nerve. 


STIMULATION  OF  MUSCLE 


715 


Stimulation  by  the  Voltaic  Current. — While  the  current  continues  to 
pass  through  a  nerve  without  any  sudden  or  great  change  in  its  in- 
tensity, there  is  no  stimulation,  and  the  muscle  connected  with  the 
nerve  remains  at  rest.  The  same  is  true  of  striated  muscle  when  a 
weak  current  is  passed  directly  through  it.  But  in  muscle  the  con- 
stancy of  the  rule  is  more  and  more  frequently  broken  by  exceptional 
results  as  the  current  is  strengthened,  a  state  of  permanent  contrac- 
tion being  very  apt  to  show  itself  during  the  wliole  time  of  flow  (Wundt) 
(Fig.  239).  Above  a  certain  intensity  of  current  a  greater  or  less 
degree  of  permanent  contraction  is  invariably  produced.  Tliis  is  some- 
times called  the  '  closing  tetanus.'  It  is,  however,  not  a  true  tetanus, 
but  a  tonic  contraction,  which  is  strongest  in  the  neighbourhood  of  the 
kathode,  and  does  not  spread  far  from  it.  A  similar  condition,  the 
so-called  galvanotonus.  is  normally  seen  in  human  muscles  when  they  or 
their  motor  nerves  are 
traversed  by  a  stream 
of  considerable  inten- 
sity. Under  certain  con- 
ditions, too — e.g..  when 
a  strong  current  is 
allowed  to  flow  for  a 
comparatively  long  time 
through  a  muscle — the 
muscle  remains  contrac- 
ted after  the  opening  of 
the  current  (so-called 
'  opening  or  Ritter's  tet- 
anus ').  Smooth  muscle 
is  excited  to  contraction 
even  when  a  voltaic  cur- 
rent is  very  gradually 
passed  into  it  and  slow- 
ly increased,  and  again 
when  it  is  caused  very 
gradually  to  disappear. 
But  striped  muscle  is 
not  stimulated  under 
these  conditions. 

For  nerve,  and  with  these  qualifications  for  muscle,  too,  the  law 
holds  that  the  voltaic  current  stimtdates  at  tnake  and  at  break,  but  not 
during  its  passage.  Or,  generalizing  this  a  little,  since  it  has  been 
shown  that  a  sudden  increase  or  decrease  in  the  strength  of  a  current 
already  flowing  also  acts  as  a  stimulus,  we  may  say  that  the  voltaic 
current  stimulates  only  when  its  intensity  is  suddenly  and  sufficiently 
increased  or  diminished,  but  not  while  it  remains  constant.* 

When  a  strong  current  is  closed  through  a  muscle  there  is  an  im- 
mediate sharp  contraction  (initial  contraction).  The  muscle  then 
promptly  relaxes,  but  incompletely.  When  the  current  is  opened, 
there  is  another  contraction  (Fig.  240).  The  force  of  the  initial  con- 
traction, as  measured  by  the  resistance  necessary'  to  prevent  it,  is 
greater  than  that  of  the  tonic  contraction  which  follows  it. 

A  second  law  of  great  theoretical  importance  is  that  of  polar  stimula- 
tion. At  make  the  stimulation  occurs  only  at  the  kathode  ;  at  break  only 
at  the  anode.     This  is  true  both  for  muscle  and  nerve,  but  it  is  most 

*  This  law  of  Du  Bois-Keymond  has  been  questioned  by  Hoorweg  and  others. 
It  seenxs  to  need  modification,  but  the  subject  cannot  be  discussed  here. 


Fig.  240. — Tonic  Contraction  during  and  after  Flow 
of  Voltaic  Current.  Curve  from  frog's  gastroc- 
nemius. At  M  constant  current  closed,  at  B  broken. 
Contracture  continues  after  opening  of  current. 
Time  trace,  two-second  intervals. 


7i6         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

directly  and  simply  demonstrated  on  muscle.  A  long  parallel-fibred 
curarized  muscle  is  supported  about  its  middle;  the  two  ends,  which 
hang  down,  are  connected  with  levers  writing  on  a  revolving  drum,  and 
a  current  is  sent  longitudinally  through  the  muscle.  It  is  not  difficult 
to  see  from  the  tracings  that  at  make  the  lever  attached  to  the  kathodic 
end  moves  first,  and  that  the  other  lever  only  moves  when  the  contrac- 
tion started  at  the  kathode  has  had  time  to  reach  it  in  its  progress 
along  the  muscle.  Similarly,  at  break  the  lever  connected  with  the 
anodic  end  moves  first.  The  law  of  polar  excitation  holds  both  for 
striated  and  -for  smooth  muscle.  Not  only  is  there  no  excitation  of 
unstriped  muscle  at  the  anode  on  closure  of  the  current,  but  a  previ- 
ously existing  contraction  disappears.  For  skeletal  muscle  the  make  is 
stronger  than  the  break  contraction.  It  has  not  been  proved  that  this 
is  the  case  for  smooth  muscle. 


Section  III. — Physical  and   Mechanical  Phenomena  of  the 
Muscular  Contraction. 

When  a  muscle  contracts,  its  two  points  of  attachment,  or,  if  it 
be  isolated,  its  two  ends,  come  nearer  to  each  other;  and  in  exact 
proportion  to  this  shortening  is  the  increase  in  the  average  cross- 
section.  The  contraction  is  essentially  a  change  of  form,  not  a 
change  of  volume.  The  most  delicate  observations  fail  to  detect 
the  smallest  alteration  in  bulk  (Ewald).  Living  fibres  kept  con- 
tracted by  successive  stimuli  can  be  examined  under  the  microscope ; 
or  fibres  may  be  '  fixed  '  by  reagents  like  osmic  acid,  and  sometimes 
a  very  good  opportunity  of  studying  the  microscopic  changes  in 
contraction  is  given  by  a  group  of  fibres  in  which  the  '  fixing  ' 
reagent  has  caught  a  wave  of  contraction,  and,  so  to  speak,  pinned 
it  down.  It  is  then  seen  that  the  process  of  contraction  in  the  fibre 
is  a  miniature  of  that  in  the  anatomical  muscle.  The  individual 
fibres  shorten  and  thicken,  and  the  sum-total  of  this  shortening 
and  thickening  is  the  muscular  contraction  which  we  see  with  the 
naked  eye.  The  phenomena  of  the  muscular  contraction  may 
be  classified  thus:  (i)  Optical,  (2)  Mechanical,  (3)  Thermal, 
(4)'  Chemical,  (5)  Sonorous,  (6)  Electrical.  (5)  will  be  treated  under 
'  Voluntary  Contraction  '  ;  (6)  in  Chapter  XV. 

(i)  Optical  Phenomena — Microscopic  Structure  of  Striped  Muscle. — 

The  structure  of  striped  muscle  has  long  been  the  enigma  of  histology; 
and  the  labours  of  many  distinguished  men  have  not  sufiiced  to  make 
it  clear.  On  the  contrary,  as  investigations  have  multiplied,  new 
theories,  new  interpretations  of  what  is  to  be  seen,  have  multiplied  in 
proportion,  and  a  resolute  brevity  has  become  the  chief  duty  of  a  writer 
on  elementary  pliysiology  in  regard  to  the  whole  question. 

The  muscle-fibre,  the  unit  out  of  which  the  anatomical  muscle  is 
built  up,  is  surrounded  by  a  structureless  membrane,  the  sarcolemma. 
The  length  and  breadth  of  a  fibre  vary  greatly  in  different  situations. 
The  maximum  length  is  about  4  cm. ;  the  breadth  may  be  as  much 
as  70  fi  and  as  little  as  10  ft.  When  we  come  to  analyze  the  muscle- 
fibre  and  to  determine  out  of  what  units  it  is  built  up,  the  difficulty 
begins.     The  fibre  shows  alternate  dim  and  clear  transverse  stripes,  and 


OPTICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION      717 

can  actually  be  split  up  into  discs  by  certain  reagents.  It  also  shows 
a  longitudinal  striation,  and  can  be  separated  into  fibrils.  Some  have 
supposed  that  the  discs  are  the  real  structural  units  which,  piled  end 
to  end,  make  up  the  fibre.  The  fibrils  they  consider  artificial.  This 
view  IS  erroneous.  It  seems  certain  that  the  fibres  are  built  up  from 
fibrils  ranged  side  by  side,  and  that  the  discs  are  artificial.  The  con- 
tents of  the  muscle-fibre  appear  to  consist  of  two  functionally  different 
substances,  a  contractile  substance,  and  an  interstitial,  perhaps  nutri- 
tive, non-contractile  material  of  more  fluid  nature.  The  contractile 
substance  is  arranged  as  longitudinal  fibrils  embedded  in  interfibrillar 
matter  (sarcoplasm).  In  a  muscle  impregnated  with  chloride  of  gold 
the  interfibrillar  matter  appears  as  a  network. 

Schafer  has  described  the  contractile  elements  of  the  muscle-fibre 
(Figs.  241,   242)  as  fine  columns  (sarcostyles),  divided  into  segments 

(sarcomeres)     by    thin    transverse 
1  unrnnnTimmHwwMWMuti  discs  (Krause's  membranes),  occu- 

6-5'amnm«,t,„..,SjiiT!Wii         Uku t,A        pyiug  the  position  of  the  middle  of 

^..,„.,,  each  light  stripe.     Each  sarcomere 

llMjJiiiuuiul'linnillliniHIIIilHidU^  contains  a  sarcous  element  (a  por- 
tion of  the  dark  stripe)  with  a  clear 
substance  at  its  ends,  filling  up  the 


-3 


Fig.  241. — Living  Muscle  of  Water- 
Beetle  (highly  magnified)  (Schafer). 
5,  sarcolemma  ;  a,  dim  stripe  ; 
b,  bright  stripe;  c,  row  of  dots  in 
bright  stripe,  which  appear  to  be 
the  enlarged  ends  of  rod-shaped 
particles,  d,  but  in  reality  represent 
expansions  of  the  interstitial  sub- 
stance (sarcoplasm). 


-JC 


rig.  242. — Portion  of  Leg 
Muscle  of  Insect,  treated 
with  Dilute  Acetic  Acid 
(Schafer).  S,  sarco- 
lemma; D,  dot-like  en- 
largemen  t  of  sarcoplasm; 
K,  Krause's  membrane. 
The  sarcous  elements 
have  been  swollen  and 
dissolved  by  the  acid. 


space  between  the  sarcous  element  and  Krause's  membrane,  and  con- 
stituting a  portion  of  the  light  stripe.  The  sarcous  element  is  itself 
double,  and  if  the  fibre  be  stretched,  the  two  portions  separate  at  a 
line  which  runs  transversely  across,  the  middle  of  the  dim  stripe  (Hensen's 
line).  Schafer  considers  that  the  appearance  of  longitudinal  fibrillation 
in  the  sarcous  elements  is  due  to  the  presence  in  them  of  fine  longi- 
tudinal canals  or  pores. 

The  Krause's  membrane  of  the  individual  fibrils  is  scarcely  ever 
visible  in  an  intact  mammalian  fibre,  and  the  apparent  line  in  the  clear 
stripe  of  an  intact  fibre  is  an  optical  appearance  due  to  interference  of 
light.  Kiihne,  who  was  fortunate  enough  to  find  one  day  a  small 
nematode  worm  n^oving  in  the  interior  of  a  fibre,  saw  it  pass  along 
the  fibre  with  perfect  freedom,  ignoring  Krause's  membrane.  Possibly, 
however,  it  was  moving  in  the  sarcoplasm,  the  fibrils  being  simply 
pushed  aside. 


7i8        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Changes  during  Contraction — Theories  of  Contraction. — In  contractions, 
according  to  Schafer,  the  clear  substance  between  Krause's  membrane 
and  the  sarcous  element  passes  into  the  canals,  which  are  open  towards 
Krause's  membrane,  but  closed  towards  Hensen's  line.  The  sarcous 
element  therefore  swells  up,  and  the  sarcomere  is  shortened.  In  the 
extended  muscle  the  clear  substance  leaves  the  pores  of  the  sarcous 
element,  and  accumulates  in  the  space  between  it  and  Krause's  mem- 
brane. The  sarcomere  is  thus  lengthened  and  narrowed.  While  the 
existence  of  Schafer's  pores  is  not  admitted  by  all  observers,  there  is  a 
pretty  general  agreement  that  the  sarcomere,  like  the  cytoplasm  of  an 
amoeboid  cell,  does  consist  of  two  substances,  one  of  which  (the  hyalo- 
plasm of  the  cell,  the  clear  material  of  the  sarcomere)  interpenetrates 
the  other  (spongioplasm  of  the  cell,  substance  of  the  sarcous  element) ; 
and  that  in  relaxation  the  clear  fluid  passes  from  the  sarcous  element 
to  the  ends  of  the  sarcomeres,  whereas  in  contraction  it  passes  in  the 
reverse  direction  into  the  sarcous  elements.  Whether  the  fluid  passes 
into  and  out  of  the  meshes  of  an  actual  network,  or  along  actual  physical 
pores  in  the  sarcous  element,  or  whether  it  is  transferred  by  some 
process  like  molecular  imbibition  (p.  420),  need  not  be  discussed  here, 
since  it  is  not  definitely  known.  The  fundamental  question  by  what 
process  the  transference  is  determined  when  the  muscle  is  excited  also 
remains  unsettled.  So  far  as  is  known  at  present,  it  is  probable  that 
the  mechanical  energy  of  the  contracting  muscle  must  be  derived  from 
the  transformation  of  chemical  energy  into  one  of  three  forms :  energy 
associated  with  osmotic  processes,  energy  associated  with  imbibition, 
and  energy  associated  with  changes  of  surface  tension.  It  is  not  diffi- 
cult to  see  that  a  sudden  increase  in  the  osmotic  concentration  in  the 
sarcous  element,  due  to  the  breaking  up  of  large  molecules  or  colloid 
aggregates  into  small  molecules,  or  the  liberation  of  electrolytes  from 
the  colloids,  might  lead  to  the  rapid  passage  of  water  into  it  from 
the  bright  bands.  A  sudden  change  of  permeability  of  the  sarcous 
.  elements  for  dissolved  substances  in  the  clear  fluid  would  have  a 
similar  effect.  The  same  is  true  of  a  change  in  their  power  of  imbibi- 
tion. But,  according  to  Bernstein,  it  is  scarcely  to  be  supposed  that 
the  extraordinarily  rapid  movement  of  water  molecules  which  must 
occur  in  contraction  can  be  accounted  for  either  by  osmosis  or  by  im- 
bibition. A  more  plausible  theory  is  that  the  surface  tension — say 
between  the  substance  of  the  sarcous  element  and  the  clear  fluid^ — is 
altered.  That  the  shortening  of  the  muscle  in  fatigue  (p.  723)  and 
rigor  (p.  748),  as  well  as  its  shortening  in  normal  contraction,  is  due  in 
some  way  to  the  liberation  of  metabolic  products,  especially  lactic  acid, 
is  a  theory  of  some  standing,  and  fresh  evidence  in  its  favour  has  been 
recently  supplied.  Thus  it  has  been  pointed  out  that  the  course  of 
heat  production  in  the  active  muscle,  and  its  relation  to  the  time  of 
the  mechanical  response,  and  the  development  and  time  relations  of 
the  electrical  change  which  precedes  that  response,  can  be  very  naturally 
explained  on  the  supposition  that  the  liberation  of  lactic  acid  on  or 
near  some  surface  in  the  contractile  substance  is  an  essential  factor  in 
the  contraction  (Mines,  etc.).  It  is  known  that  in  the  presence  of  acid 
on  the  surface  of  certain  colloid  structures  shortening  occurs  (Fischer 
and  Strictman). 

The  substance  of  the  sarcous  element  which  foriris  the  dark  stripe 
is  doubly  refracting,  and  therefore  rotates  the  plane  of  polarization, 
but  the  clear  substance  of  the  light  stripe  is  singly  refracting.  When 
an  uncontracted  fibre  is  viewed  with  crossed  nicols,  the  dim  stripe 
accordingly  appears  bright  in  the  otherwise  dark  field.  In  the  con- 
tracted fibre  the  doubly  refractive  material  remains  in  the  stripe  which 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     719 


is  dim  in  ordinary  light.  Tlierc  is  no  transference  of  it,  but,  according 
to  most  writers,  tlie  bands  wliich  are  dim  in  ordinary  liglit  increase  in 
size  l)y  tlic  tr.insfcrcntc  of  iiiiuid  frum  the  isotropous  band. 

Diffraction  Spectrum  of  Muscle. — When  a  beam  of  white  light  passes 
through  a  striped  muscle,  it  is  broken  up  into  its  constituent  colours, 
and  a  series  of  diffraction  spectra  are  produced,  just  as  happens  when 
the  light  passes  through  a  diffraction  grating  (a  piece  of  glass  on  which 
are  ruled  a  number  of  line  parallel  ecjuidistant  lines).  The  nearer  the 
lines  are  to  each  other,  the  greater  is  the  displacement  of  a  ray  of  light 
of  any  given  wave-length.  It  has  accordingly  been  found  that  when  a 
muscular  fibre  contracts,  the  amount  of  displacement  of  the  diffraction 
spectra  increases.  At  the  same  time  the  whole  fibre  becomes  more 
transparent. 

(2)  Mechanical  Phenomena. — The  muscular  contraction  may  be 
graphically  recorded  by  connecting  a  muscle  with  a  lever  which  is 
moved  either  by  its  shortening  or  by  its  thickening.  The  lever  writes 
on  a  blackened  surface,  which  must 
travel  at  a  uniform  rate  if  the  form 
and  time-relations  of  the  muscle 
curve  are  to  be  studied,  but  may  be 
at  rest  if  only  the  height  of  the  con- 
tract ion  is  to  be  recorded.  The  whole 
arrangement  for  taking  a  muscle- 
tracing  is  called  a  myograph  (Fig. 
278,  p.  785).  The  duration  of  a 
'  twitch  '  or  single  contraction  (in- 
cluding the  relaxation)  of  a  frog's 
muscle  is  usually  given  as  about 
one-tenth  of  a  second,  but  it  may 
vary  considerably  wdth  temperature, 
fatigue,  and  other  circumstances. 
It  is  measured  by  the  vibrations  of 
a  tuning-fork  written  immediately 
below  or  above  the  muscle  curve. 
When  the  muscle  is  only  slightly 
weighted,  it  but  very  gradually 
reaches  its  original  length  after  con- 
traction, a  period  of  rapid  relaxation 
being  followed  by  a  period  of  '  resi- 
dual contraction,'  during  which  the 

descent  of  the  lever  towards  the  base-line  becomes  slower  and  slower, 
or  stops  altogether  some  distance  above  it.  The  duration  of  tho  con- 
traction of  smooth  muscle  evoked  by  a  single  momentary  stimulus  is 
much  greater  than  that  of  stiiped  muscle  (two  to  seven  seconds  for  the 
rabbit's  ureter;  five  to  fifteen  seconds  for  the  cat's  nictitating  mem- 
brane; one  to  two  minutes  for  the  frog's  stomach). 

Latent  Period. — If  the  time  of  stimulation  is  marked  on  the  tracing, 
it  is  found  that  the  contraction  does  not  begin  simultaneously  with  li, 
but  only  after  a  certain  interval,  which  is  called  the  latent  period. 

This  can  be  measured  by  means  of  the  spring  myograph  (Fig.  224) 
or  of  the  pendulum  myograph,  a  pendulum  which  in  its  swing  carries 
a  smoked  plate  against  the  writing-point  of  a  lever  connected  with  a 
muscle.  The  carrier  of  the  recording  plate  opens,  at  a  definite  point 
in  its  passage,  a  key  in  the  primary  coil  of  an  induction  machine,  and 
so  causes  a  shock  to  be  sent  through  the  muscle  or  nerve,  which  is  con- 
nected with  the  secondary.  The  precise  point  at  which  the  stimulus 
is  thrown  in  can  be  marked  on  the  tracing  by  carefully  bringing  the 


Fig.  243. — Living  Muscular  Fibre  (from 
Geotrupes  stercorarius).  i,  in  or- 
dinary; 2,  in  polarized  light.  (Van 
Gehuchten.)  In  living  muscle  (at 
least  in  fibres  which  are  not  extended) 
in  contrast  to  dead  muscle  after  treat- 
ment with  reagents,  the  doubly  re- 
fracting or  anisotropous  substance  is 
present  in  the  greater  part  of  the  fibre ; 
and  with  crossed  nicols  the  position  of 
the  singly  refracting  or  isotropous 
material  is  indicated  only  by  narrow 
transverse  black  lines  or  rows  of  dark 
dots. 


720        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

plate  to  the  position  in  which  the  key  is  just  opened,  and  allowing 
the  lever  to  trace  here  a  vertical  line  (or,  rather,  an  arc  of  a  circle). 
The  portion  of  the  time-tracing  between  this  line  and  a  parallel  line 
drawn  through  the  point  at  which  the  contraction  begins  gives  the 
latent  period. 

Helmholtz  measured  the  length  of  the  latent  period  by  means  ot  the 
principle  of  Pouillet,  that  the  deflection  of  a  magnet  by  a  current  of 
given  strength  and  of  very  short  duration  is  proportional  to  the  time 
during  which  the  current  acts  on  the  magnet.  He  arranged  that  at 
the  moment  of  stimulation  of  the  muscle  a  current  should  be  sent 
through  a  galvanometer,  and  should  be  broken  by  the  contraction  of 
the  muscle  the  moment  it  began.  In  this  way  he  obtained  the  value 
of  1^0  second  for  the  latent  period  of  frog's  muscle.     The  tendency  of 


Fig.  244. — Spring  Myograph.  A,  B,  iron  uprights,  between  which  are  stretched  the 
guide-wires  on  which  the  travelling  plate  a  runs;  k,  pieces  of  cork  on  the  guides 
to  gradually  check  the  plate  at  the  end  of  its  excursion,  and  prevent  jarring; 
b,  spring,  the  release  of  which  shoots  the  plate  along;  h,  trigger-key,  which  is 
opened  by  the  pin  d  on  the  frame  of  the  plate. 

later  observations  has  been  to  make  the  latent  period  shorter.  Burdon 
Sanderson  found  that  the  change  of  form  begins  in  unweighted  or  very 
slightly  weighted  muscle  with  direct  stimulation  in  j^g  second  after, 
and  the  electrical  change  (p.  797)  simultaneously  with,  the  excitation. 
It  is  known  that  the  apparent  latent  period  depends  upon  the  resistance 
which  the  muscle  has  to  overcome  in  beginning  its  contraction. 

The  maximum  shortening,  or  '  height  of  the  lift,'  depends  upon  the 
length  of  the  muscle,  the  direction  of  the  fibres,  the  strength  of  the 
stimulus,  the  excitability  of  the  tissue,  and  the  load  it  has  to  raise. 

In  a  long  muscle,  other  things  being  equal,  the  absolute  shortening, 
and  therefore  the  maximum  height  of  the  curve,  will  be  greater  than 
in  a  short  muscle;  in  a  muscle  with  fibres  parallel  to  its  length — the 
sartorius,  for  instance  —  it  will  be  greater  than  in  a  muscle  like  the 
gastrocnemius,  with  the  fibres  directed  at  various  angles  to  the  long 
axigi     For  stimuli  less  than  maximal,  the  absolute  contraction  increases 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION     721 


with  the  strength  of  stimulation,  and  a  given  stimulus  will  cause  a 
greater  contraction  in  a  muscle  with  a  given  excitability  than  in  a 
muscle  which  is  less  excitable.  Under  ordinary  experimental  condi- 
tions at  least,  weak  stimuli  cause  a  smaller  contraction  than  strong, 
not  only  because  each  stimulated  fibre  contracts  less,  but  because  a 
smaller  number  of  fibres  are  excited  (p.  155).  The  objects  used  for  the 
study  of  muscular  contraction  contain  many  fibres,  and  it  is  not  in 


Fig.  245. — Curve  of  a  Single  Muscular  Contraction  or  Twitch  taken  on  Smoked  Glass 
with  Spring  Myograph  and  photographed.  Vertical  line  A  marks  the  point  at 
which  the  muscle  was  stimulated;  time  tracing  shows  ^^  of  a  second  (reduced). 

general  possible  to  distribute  the  stimulus  equally  to  all.  This  is  true 
for  smooth  muscle  as  well  as  for  striped.  Finally,  increase  of  the  load 
per  unit  of  cross-section  of  the  muscle  diminishes  above  a  certain  limit 
the  '  height  of  the  lift.' 

Influences  which  affect  the  Time-Relations  of  the  Muscular  Contrac- 
tion.— Many  circumstances  affect  the  form  of  the  muscle  curve  and  its 
time-relations. 

(a)  Influence  of  the  Load — Isotonic  and  Isometric  Contraction. — The 
first  effect  of  contraction  is  to  suddenly  stretch  the  muscle,  and  the 
more  the  muscle  is  loaded  the  greater  will  this 
elongation  be.  So  that  at  the  beginning  of  the 
actual  shortening  part  of  the  energy  of  contraction 
is  already  expended  without  visible  effect,  and  has 
to  be  recovered  from  the  elastic  reaction  during 
the  ascent  of  the  lever. 

The  contraction  of  a  muscle  loaded  by  a  weight 
which  is  not  increased  or  diminished  during  the 
contraction  is  said  to  be  isotonic,  for  here  the 
tension  of  the  muscle  is  the  same  throughout,  and 
its  length  alters.  When  the  muscle  is  attached  very 
near  the  fulcrum  of  the  lever,  so  that  it  acts  upon 
a  short  arm,  while  the  long  arm  carrying  the 
writing-point  is  prevented  from  moving  much  by 
a  spring,  the  muscle  can  only  shorten  itself  very 
slightly;  but  the  changes  of  tension  in  it  will  be 
related  to  those  in  the  spring,  and  therefore  to  the 
curve  traced  by  the  writing-point.  Such  a  curve 
is  called  isometric,  since  the  length  of  the  muscle 
remains  almost  unaltered.  In  the  body  muscles 
usually  contract  under  conditions  more  nearly 
allied  to  those  of  the  isometric  than  to  those  of 
the  isotonic  contraction.- 

The  work  done  by  a  muscle  in  raising  a  weight  is  equal  to  the  product 
of  the  weight  by  the  hciglit  to  which  it  is  raised.  Beginning  with  no 
load  at  all,  it  is  found  that  the  weight  can  be  increased  up  to  a  certain 
limit  without  diminishing  the  height  of  the  contraction;  perhaps  the 
height  may  even  increase.  Up  to  this  limit,  then,  the  work  evidently 
increases  with  the  load.     If  the  weight  is  made  still  greater,  the  con- 

46 


Fig.  246.  —  Contrac- 
tions of  Smooth  Mus 
cle:  Cat's  Bladder 
(C.  C.  Stewart). 
Stimulated  with  pro- 
gressively stronger 
induction  shocks. 
The  lowest  line  is  the 
time  trace  (lo-second 
intervals).  Immedi- 
ately below  the  mus. 
cular  contractions  are 
marked  the  points  at 
which  the  stimuli 
were  thrown  in. 


722         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

traction  becomes  less  and  less,  but  up  to  another  limit  the  increase  of 
weight  more  than  compensates  for  the  diminution  of  'lift,'  and  the 
work  still  increases.     Beyond  this,  further  increase  of  weight  can  no 


Fig.  247.— Influence  of  Load  on  the  Form  of  the  Muscle  Curve,  i,  curve  talcen  with 
unloaded  lever;  2,  3,  4,  weight  successively  increased;  5.  abscissa  line:  time  trace, 
y^  secon(i  (reduced). 

longer  make  up  for  the  lessening  of  the  lift,  and  the  work  falls  off  till 
ultimately  the  muscle  is  unable  to  raise  the  weight  at  all. 

The  '  absolute  contractile  force  '  of  an  active  muscle  may  be  measured 
by  determining  the  weight  which,  brought  to  bear  upon  the  muscle  at 


Fig!  248. —  Influence  of  Temperature  on  the  Striated  Muscle  Curve.  2,  air  teiupera- 
ture ;  i.  25° — 30°  C. ;  3,  7° — 10°  C. ;  4,  ice  in  contact  with  muscle.  The  fifth  curve 
was  taken  at  a  little  above  air  temperature. 

the  instant  of  contraction,  is  just  able  to  prevent  shortening  without 
■stretching  the  muscle.  It,  of  course,  depends,  among  other  things,  on 
the  cross-section  of  the  muscle.  During  the  contraction  the  absolute 
force  diminishes  continually,  so  that  a  smaller  and  smaller  weight  is 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     723 


sufficient  to  stop  any  further  contraction,  the  more  the  muscle  has 
already  shortened  before  it  is  api)Iied.  At  the  maximum  of  the  con- 
traction the  absolute  force  is  zero.  Hence  a  muscle  works  under  the 
most  favourable  conditions  wlien  tlie  weight  decrciises  as  it  is  raised, 
and  this  is  the  case  with  many  of  the  muscles  of  the  body.  During 
flexure  of  the  forearm  on  the  elbow,  with  the  upper  arm  horizontal,  a 
weight  in  the  hand  is  felt  less  and  less  as  it  is  raised,  since  its  moment, 
which  is  proportional  to  its  distance  from  a  vertical  line  drawn  through 
the  lower  end  of  the  humerus,  continually  diminishes. 

{b)  lujlueyice  of  Temperature  on  the  Musciilay  Contraction. — Increase 
of  temperature  of  the  muscle  up  to  a  certain  limit  diminishes  the  latent 
period  and  the  length  of  the  curve,  and  increases 
the  height  of  the  contraction,  but  beyond  this 
limit  the  contractions  are  lessened  in  height 
(Fig.  248).  Marl<«d  diminution  of  temperature 
causes,  in  general,  an  increase  in  the  latent  period 
and  length,  and  a  decrease  in  the  height  of  the 
contraction.  In  the  heart  the  effect  of  cold  in 
strengthening  the  beat  is  often  very  marked. 
Temperature  affects  the  contraction  curve  of 
smooth  muscle  much  in  the  same  way  as  that 
of  striated  muscle  (Fig.  249). 

(c)  Influence  of  Previous  Stimulation — Fatigue. 
— If  a  muscle  is  stimulated  by  a  series  of 
equal  shocks'  thrown  in  at  regular  intervals. 


Fig.  249. — Influence  of  Temperature  on  the  Smooth  Muscle  Curve:  Cat's  Bladder 
(C.  C.  Stewart).     Contractions  at  different  temperatures  with  the  same  strength 
■  of  stimulus.    The  temperatures  (Centigrade)  are  marked  on  the  curves. 

.1  .      . 

and  the  contractions  recorded,  it  is  seen  that  at  first  each  curve 
overtops  its  predecessor  by  a  small  amount.  This  phenomenon, 
which  is  regularly  observed  in  fresh  skeletal  muscle  (Fig.  253), 
although  it  was  at  one  time  supposed  to  be  peculiarly  a  property 
of  the  muscle  of  the  heart  (Fig.  254),  is  called  the  '  staircase,'  and 
seems  to  indicate  that  within  limits  the  muscle  is  benefited  by 
contraction  and  its  excitability  increased  for  a  new  stimulus.  Soon, 
however,  in  an  isolated  preparation,  the  contractions  begin  to  decline 
in  height,  till  the  muscle  is  at  length  utterly  exhausted,  antl  reacts 
no  longer  to  even  the  strongest  stimulation  (Figs.  251,  252,  279). 

A  conspicuous  feature  of  the  contraction-curves  of  fatigued 
muscle  is  the  progressive  lengthening,  which  is  much  more  marked 
in  the  descending  than  in  the  ascending  periods;  in  other  words, 


724        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

relaxation  becomes  more  and  more  difficult  and  imperfect  (Fig.  279, 
p.  787) .  In  smooth  muscle  (cat's  bladder  or  ring  from  frog's  stomach) 
fatigue  can  be  very  easily  demon- 
strated in  the  same  way,  and  the 
curves  present  similar  features,  with 
the  exception  that,  instead  of  be- 
coming longer  in  fatigue,  the  suc- 
cessive contractions  become  shorter. 
It  is  by  no  means  so  easy  to 
fatigue  a  muscle  still  in  connection 
with  the  circulation  as  an  isolated 
muscle.  But  even  the  latter,  if  left 
to  itself,  will  to  some  extent  re- 
cover, and  be- again  able  to  con- 
tract, although  exhaustion  is  now 
more  readily  induced  than  at  first. 


Fig.  251. — Fatigue  Curve  of  Muscle-. 
Frog's  Gastrocnemius.  The  arrange- 
ment with  which  the  curve  figured 
was  ©btained  was  a  so-called  auto- 
matic muscle  interruptor  (Fig.  «5o). 
A  wire  on  the  lever  is  made  to  close 
and  open  the  primary  circuit  of  an 
inductorium,  the  muscle  or  nerve 
being  connected  with  the  secondary. 
Every  time  the  needle  touches  the 
mercury  the  mwscle  is  stimulated 
automatically. 


Fig.  250. — Automatic  Muscle  Interruptor. 
K,  battery;  P,  primary;  S,  secondary  coil; 
A,  axis  of  lever;  N,  needle;  Hg,  mercury 

Ciip. 


In  man,  muscular  fatigue  can  be  studied  by  means  of  an  arrange- 
ment called  an  ergograph  (Fig.  255).    A  record  of  successive  con- 


Ijg  252. — Fatigue  Curve  taken  on  a  Slowly-moving  Drum  (reduced  to  Half):  Frog's 
Gastrocnemius.  Excited  through  the  sciatic  nerve  by  maximiU  shocks  once  in 
six  seconds. 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION    725 

tractions,  say,  of  one  of  the  flexor  muscles  of  a  finger,  in  raising 
a  weight  (isotonic  method)  or  in  deforming  a  spring  (isonietnc 
method)  is  taken  on  a  drum.  When  the  contractions  are  repeated 
every  second,  or  every  half-second,  distinct  evidence  of  fatigue  is 
seen  on  the  tracing  after  a  longer 
or  shorter  period,  according  to  the 
conditions. 

What  is  the  cause  of  muscular 
fatigue  ?  An  exact  answer  is  not 
possible  in  the  present  state  of  our 
knowledge,  but  we  may  fairly  con- 
clude that  in  an  isolated  preparation 
it  is  twofold:  (i)  Waste  products, 
among  which  some  are  so  directly 
related  to  the  onset  of  fatigue  as  to 
deserve  the  name  of  '  fatigue  sub- 
stances,' are  formed  by  the  active 
muscle  faster  than  they  can  be  re- 
moved, oxidized  or  otherwise  decom- 
posed.  (2)  The  material  necessary  for  ""f,  J»rFf:gi"T.;„ulaUof' by 
contraction  is  used  up  more  quickly  an  automatic  arrangement, 
than  it  can  be  reproduced  or  brought 

to  the  place  where  it  is  required.  That  the  accumulation  of  fatigue 
products  has  something  to  do  with  the  exhaustion  is  shown  by 
the  fact  that  the  muscles  of  a  frog,  exhausted  in  spite  of  the  con- 
tinuance of  the  circulation,  can  be  restored  by  bleeding  the  animal, 
or  washing  out  the  vessels  with  physiological  salt  solution,  while 
injection  of  a  watery  extract  of  exhausted  muscle  into  the  blood- 


Fig.  254. — '  Staircase  '  in  Cardiac  Muscle.  Contractions  recorded  ou  a  much  more 
quickly  moving  drum  than  in  Fig.  253.  The  contractions  were  caused  by  stimu- 
lating a  heart  reduced  to  standstill  by  the  first  Stannius'  ligature  (p.  197).  The 
contractions  gradually  increase  in  height. 

vessels  of  a  curarized  muscle  renders  it  less  excitable  (Ranke). 
This  observer  supposed  that  it  was  specially  the  removal  of  the  acid 
products  of  contraction  which  restored  the  muscle.  Such  acid 
products  as  carbon  dioxide  and  lactic  acid,  or  the  lactates  which  it 
may  form  with  bases  in  the  blood,  lymph  or  tissues,  when  they 
act  on  muscle  in  more  than  a  certain  concentration,  produce  the 


726        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

same  effects  on  its  power  of  contraction  as  are  produced  by  fatigue, 
and  there  is  some  reason  to  suppose  that  lactic  acid  is  the  most 
influential  of  the  fatigue  substances.  In  smaller  concentration, 
on  the  contrary,  they  increase  the  excitability  of  the  muscle,  and, 
according  to  Lee,  the  phenomenon  of  the  '  staircase  '  is  due  to  the 
augmenting  action  of  these,  and  perhaps  other  fatigue  substances, 
before  they  have  accumulated  sufficiently  to  cause  fatigue. 

The  lack  of  oxygen  holds  a  conspicuous  place  among  the  con- 
ditions which  permit  an  excessive  accumulation  of  fatigue  substances, 
and  may  contribute  also  to  the  failure  of  the  processes  normally 
going  on  in  the  muscle  which  replenish  the  store  of  materials 
needed  for  contraction.  An  isolated  muscle  is  necessarily  an 
asphyxiated  muscle,  and  the  favourable  action  of  an  atmosphere 
of  oxygen  on  restoration  of  its  contractile  power  after  exhaustion 


Fig.  255. — Ergograph  (Mosso's,  modified  by  Lombard). 

(Fig.  123,  p.  265)  shows  that  asphyxia  is  itself  an  important  factor 
in  the  onset  of  fatigue.  Injection  of  arterial  blood,  or  even  of 
an  oxidizing  agent  like  potassium  permanganate,  into  the  vessels 
of  an  exhausted  muscle  causes  restoration  (Kronecker).  The 
depletion  of  the  available  store  of  carbo-hydrate  in  the  form  of 
glycogen  (and  dextrose)  seems  to  be  another  factor  in  fatigue, 
although  not  the  chief  direct  cause  of  the  phenomena  associated 
with  that  condition. 

Seat  of  Exhaustion  in  Fatigue. — When  a  fatigued  muscle  responds 
no  longer  to  indirect  stimulation,  it  can  still  be  directly  excited. 
The  seat  of  exhaustion  must  therefore  be  either  the  nerve-trunk 
or  the  nerve-endings.  It  is  not  the  nerve-trunk  which  is  first 
fatigued,  for  this  still  shows  the  negative  variation  (p.  797)  on  being 
excited.     And  if  the  two  sciatic  nerves  of  a  frog  or  rabbit  be  stimu- 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     727 

lated  continuously  with  interrupted  currents  of  equal  strength, 
while  the  excitation  is  prevented  from  reaching  the  muscles  of  one 
limb  till  those  oi  the  other  cease  to  contract,  it  will  be  found  that 
when  the  '  block  '  is  removed  the  corresponding  muscles  contract 
vigorously  on  stimulation  of  their  nerve.  The  passage  of  a  constant 
current  through  a  portion  of  the  nerve  or  the  application  of  ether 
between  the  point  of  stimulation  and  the  muscles  may  be  used  to 
prevent  the  excitation  from  passing  down  (p.  786).  Or  a  dose  of 
curara  just  sufficient  to  paralyze  the  motor  innervation  may  be 
given  to  a  rabbit,  and  the  animal  kept  alive  by  artificial  respiration. 
The  sciatic  is  now  stimulated  for  many  hours.  As  soon  as  the 
influence  of  the  curara  begins  to  wear  off,  the  muscles  of  the  leg 
contract. 

The  possible  seats  of  fatigue  caused  by  voluntary  muscular  con- 
traction are  (i)  the  muscle;  (2)  the  nerve-endings  (or  the  receptive 
substances  in  the  muscles,  p.  713);  (3)  the  nerve-trunk;  and  (4)  the 
path  of  the  voluntary  motor  impulses  in  the  central  nervous 
system,  which  includes  the  pyramidal  cells  in  the  motor  region  of 
the  cerebral  cortex  (p.  847),  the  fibres  of  the  pyramidal  tract,  and 
the  motor  cells  in  the  anterior  horn  of  the  spinal  cord. 

The  two  weak  links  in  this  chain  appear  to  be  the  motor  nerve- 
endings  and  the  muscles.  The  nerve-fibres,  whether  peripheral 
or  central,  are  certainly  the  strongest  link.  Ergographic  experi- 
ments have  hitherto  yielded  results  too  discordant  to  justify  any 
very  definite  statement  as  to  the  point  at  which  the  chain  snaps  in 
complete  fatigue,  if,  indeed,  it  always  necessarily  breaks  at  the  same 
point.  The  muscles  and  motor  endings  appear  to  be  always  affected. 
The  position  of  the  nerve  centres,  including  the  synapses  (p.  824), 
is  in  doubt.  That  the  synapses  easily  lose  their  power  of  con- 
ducting nerve  impulses  under  the  influence  of  repeated  excitations 
is  indicated  by  the  experiments  of  Sherrington  on  fatigue  of  reflex 
mechanisms  in  which  two  or  more  afferent  paths  can  cause  discharge 
along  a  common  efferent  path  (p.  874).  When  excitation  of  one 
of  the  afferent  pat  lis  has  ceased  to  be  effective,  the  reflex  contrac- 
tions can  still  be  obtained  on  exciting  the  other.  In  this  case  the 
motor  neuron  from  cell-body  to  nerve-ending  and  the  muscle  are 
ehminated  as  the  seats  of  the  fatigue  block.  Whether  the  tem- 
porary loss  of  conduction  in  this  case  is  comparable  to  the  fatigue 
of  muscle,  or  is  a  perfectly  different  phenomenon  ('  pseudo- fatigue  ' 
of  Lee),  scarcely  bears  on  our  present  question.  For  if  '  pseudo- 
fatigue  '  of  afferent  synapses  can  cause  a  reflex  to  miss  fire,  this  at 
least  shows  that  the  conductivity  of  the  synapse  is  very  easily  affected 
by  repeated  excitation,  just  as  it  is  known  to  be  very  easily  affected 
by  anaemia.  The  fact  that  a  muscle,  completely  fatigued  by  direct 
electrical  stimulation,  can  still  be  voluntarily  contracted,  has  been 
supposed  to  indicate  that  the  voluntary  excitation  is  more  effective 


728         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

than  any  artificial  stimulus.  But  the  alternative  explanation  that 
the  electrical  stimuli  cannot  be  applied  to  a  muscle  in  situ,  so  as  to 
cause  uniform  excitation,  and  therefore  uniform  fatigue,  of  all  the 
fibres  of  the  muscle,  is  more  probable  (Hough). 

It  has  been  shown  that  the  injection  of  the  blood  of  an  animal 
exhausted  by  running  or  other  muscular  effort  into  the  circulation 
of  a  normal  animal  produces  in  the  latter  all  the  symptoms  of  fatigue. 
Here  the  fatigue-producing  substances  will  have  the  opportunity 
of  acting  on  both  the  central  and  the  peripheral  mechanisms.  There 
are  reasons  for  believing  that  the  fatigue  process  is  fundamentally 
the  same  in  different  tissues.     The  fatigue  substances  produced  in 


Fig.  256. — Influence  of  Mental  Fatigue  on  Muscular  Contraction,  i,  series  of  con- 
tractions of  flexors  of  middle  finger  before,  and  2,  series  of  contractions  imme- 
diately after,  a  period  of  three  and  a  half  hours'  hard  mental  work.  In  both 
cases  the  muscles  were  stimulated  directly  every  two  seconds  by  an  electrical 
current,  and  caused  to  raise  a  certain  weight  till  temporary  exhaustion  occurred. 
In  the  first  series  fifty-three  contractions  were  found  possible,  in  the  second  only 
twelve  (Maggiora). 

muscle,  and  not  immediately  eliminated  or  transformed  during 
active  muscular  exertion,  may  therefore  very  well  be  a  factor  in 
inducing  fatigue  of  the  central  nervous  mechanisms  in  addition  to 
the  formation  of  fatigue  products,  and  the  using  up  of  necessary 
material  in  these  mechanisms  themselves.  Conversely,  active 
and  long-continued  mental  exertion  may  occasion  muscular  fatigue 
(Fig.  256).    The  sensation  of  fatigue  is  alluded  to  in  Chapter  XVIII. 

{d)  The  Influence  of  Drugs  on  the  Contraction  of  Muscle. — The  total 
work  which  a  muscle  can  perform,  its  excitability  and  the  absolute 
force  of  the  contraction,  may  all  be  altered  either  in  the  plus  or  the 
minus  sense  by  drugs.  But  in  connection  with  our  present  subject 
those  drugs  which  conspicuously  alter  the  form  and  time-relations  of 
the  mu3  le-curve  have  most  interest.     Of  these  veratrine  is  especially 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     729 


important.  When  a  small  quantity  of  this  subslancc  is  injected  below 
the  skin  of  a  frog,  spasms  of  the  voluntary  muscles,  well  marked  in  the 
limbs,  come  on  in  a  few  minutes.  These  arc  attended  with  great 
stiffness  of  movement,  for  while  the  animal  can  contract  the  extensor 
muscles  of  its  legs  so  as  to  make  a  spring,  they  relax  ver>'  slowly,  and 
some  time  elapses  before  it  can  spring  again.  If  it  be  killed  before  the 
reflexes  are  completely  gone,  the  peculiar  alterations  in  the  form  of  the 
muscle-curve  caused  by  veratrine  will  be  most  marked.     The  poisoned 


/WVW-WA'AVWWWVWVMWWW^WTOJnailW^^ 


.VMfWV\W\VWVW\ 


Fig.  257. — Veratrine  Curve  compared  with  Normal:  Frog's  Gastrocnemius.  The 
tuning-fork  marks  hundredths  of  a  second.  Between  i  and  2  a  portion  of  the 
tracing  corresponding  to  one  and  a  half  seconds  has  been  cut  out,  and  between 
2  and  3  a  portion  corresponding  to  one  second.  The  veratrine  curve  does  not 
show  a  peak.     At  3  it  has  not  yet  fallen  to  the  base-line. 

muscle,  stimulated  directly  or  through  its  nerve,  contracts  as  rapidly 
as  a  normal  muscle,  while  the  height  of  the  curve  is  about  the  same, 
but  the  relaxation  is  enormously  prolonged  (Fig.  257).  This  effect 
seems  to  be  to  a  considerable  degree  dependent  on  temperature,  and 
it  may  temporarily  disappear  when  the  muscle  is  made  to  contract 
several  times  without  pause.  Barium  salts,  and,  in  a  less  degree,  those 
of  strontium  and  calcium,  have  an  action  on  muscle  similar  to  that  of 
veratrine.  Sometimes  the  curve  shows  a  peak  (Fig.  258),  due  to  a 
rapid  descent  of  the  lever  for  a  certain  distance.  This  is  followed  by 
a  slow  relaxation.  The 
peak  appears  to  be  analo- 
gous to  the  initial  con- 
traction when  a  strong 
voltaic  current  is  passed 
through  a  muscle,  and 
the  rest  of  the  curve  to 
tho^tonic  contraction. 

(e)  The  individuality  of 
the  muscle  itself  has  an 
influence  on  the  muscle- 
curve.  Not  only  do  the 
muscles  of  different  animals  vary  in  the  rapidity  of  contraction,  but 
there  are  also  differences  between  the  skeletal  muscles  of  the  same  animal. 

In  the  rabbit  there  are  two  kinds  of  striped  muscle,  the  red  and  the 
pale  (the  semitendinosus  is  a  red,  and  the  adductor  magnus  a  pale 
muscle),  and  the  contraction  of  the  former  is  markedly  slower  than 
that  of  the  latter.  In  many  fishes  and  birds,  and  in  some  insects,  a 
similar  difference  of  colour  and  structure  is  present. 

Even  where  there  is  no  distinct  histological  difference,  there  may  be 
great  variations  in  tlie  length  of  contraction.  In  the  frog,  for  instance, 
the  hyoglossus  muscle  contracts  much  more  slowly  than  the  gastroc- 


Fig.  258. — Veratrine  Curve:  Frog's  Gastrocnemius. 
The  curve  shows  a  peak,  the  lever  falling  a  little 
before  the  sustained  contraction  begins. 


530        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

nemius.  The  wave  of  contraction,  which  in  frogs'  striped  muscle  lasts 
only  about  0-07  second  at  any  point,  may  last  a  second  in  the  forceps 
muscle  of  the  crayfish,  though  only  half  as  long  in  the  muscles  of  the  tail. 
In  the  muscles  of  the  tortoise  the  contraction  is  also  very  slow.  The 
muscles  of  the  arm  of  man  contract  more  quickly  than  those  of  the  leg. 
Summation  of  Stimuli  and  Superposition  of  Contractions.— Hitherto 
we  have  considered  a  single  muscular  contraction  as  arising  from  a 
single  stimulus,  and  we  have  assumed  that  the  muscle  has  completed 
its  curve  and  come  back  to  its  original  length  before  the  next  stimulus 
was  thrown  in.  We  have  now  to  inquire  what  happens  when  a  second 
stimulus  acts  upon  the  muscle  during  the  contraction  caused  by  a  first 
stimulus,  or  during  the  latent  period  before  the  contraction  has  actually 
begun;  and  what  happens  when  a  whole  series  of  rapidly-succeeding 
stimuli  are  thrown  into  the  muscle. 

First  let  us  take  two  stimuli  separated  by  a  smaller  interval  than 
the  latent  period  (p.  719).  If  they  are  both  maximal— i.e.,  if  each  by 
itself  would  produce  the  greatest  amount  of  contraction  of  which  the 
muscle  is  capable  when  excited  by  a  single  stimulus — the  second  has 
no  effect  whatever ;  the  contraction  is  precisely  the  same  as  if  it  had 

never  acted.  But  if  they  are  less 
than  maximal,  the  contraction, 
although  it  is  a  single  contraction, 
is  greater  than  would  have  been 
due  to  the  first  stimulus  alone;  in 
other  words,  the  stimuli  have  been 
summed  or  added  to  each  other 
during  the  latent  period,  so  aA  to 
produce  a  single  result. 

Next  let  us  consider  the  case  of 
two  stimuli  separated  by  a  greater 
interval  than  the  latent  period,  so 
Fig.  259-— Superposition  of  Contractions,     ^i^^^    ^j^g    second    falls    into    the 
I  is  the  curve  when  only  one  stimulus     i^uscle  during  the  contraction  pro- 
is  thrown  in ;  2.  when  a  second  stimulus     ^^^^^  ,      ^^^  ^^^^     j^^  ^^^^^^  j^^^.^ 
acts  at  the  time  when  curve  i  has  nearly  different :  traces  of  two  con- 

reached  its  maximum  height.  .        .■  j.u  1 

tractions  appear  upon  the  muscle- 
curve,  the  second  curve  being  that  which  the  second  stimulus  would  have 
caused  alone,  but  rising  from  the  point  which  the  first  had  reached  at  the 
moment  of  the  second  shock  (Fig.  259).  Although  the  first  curve  is 
cut  short  in  this  manner,  the  total  height  of  the  contraction  is  greater 
than  it  would  have  been  had  only  the  first  stimulus  acted ;  and  this  is 
true  even  when  both  stimuli  are  maximal.  Under  favourable  circum- 
stances, when  the  second  curve  rises  from  the  apex  of  the  first,  the  total 
height  may  be  twice  as  great  as  that  of  the  contraction  which  one 
stimulus  would  have  caused  (p.  789).  It  is  worthy  of  note  that  striated 
muscle  has  no  power  of  summation  of  subminimal  stimuli  each  of  .which 
is  just  too  weak  to  cause  contraction.  No  matter  how  rapidly  they  are 
thrown  in,  the  muscle  remains  at  rest.  It  is  otherwise  with  smooth 
muscle.  Stimuli  which  are  singly  ineffective  cause  contraction  when 
repeated. 

Tetanus. — Not  only  may  we  have  superposition  or  fusion  of  two 
contractions,  but  of  an  indefinite  number;  and  a  series  of  rapidly 
following  stimuli  causes  complete  tetanus  of  the  muscle,  which 
remains  contracted  during  the  stimulation,  or  till  it  is  exhausted 
(Fig.  260). 


MECHANICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION     731 

The  meaning  of  a  complete  tetanus  is  readily  grasped  if,  beginning 
with  a  series  of  shocks  of  such  rapidity  that  the  muscle  can  just 
completely  relax  in  the  intervals  between  successive  stimuli,  we 
gradually  increase  the  frequency  (p.  789).  As  this  is  done,  the 
ripples  on  the  curve  become  smaller  and  smaller,  and  at  last  fade 
out  altogether.  The  maximum  height  of  the  contraction  is  greater 
than  that  produced  by  the  strongest  single  stimulus;  and  even  after 
complete  fusion  has  been  attained,  a  further  increase  of  the  fre- 
quency of  stimulation  may  cause  the  curve  still  to  rise. 


Fig.  260. — Analysis  of  Electrical  Tetanus  (reduced  to  f ).  Four  curves  showing  the 
effect  of  increasing  frequency  of  stimulation  of  the  frog's  gastrocnemius  through 
its  nerve.  In  the  lowest  curve  the  frequency  is  such  that  the  muscle  relaxes 
almost  completely  between  the  successive  contractions.  In  the  uppermost 
curve,  with  a  frequency  more  than  three  times  greater,  the  contractions  are 
almost  completely  fused.  In  all  Ihe  curves  the  fusion  becomes  more  nearly 
complete  as  stimulation  goes  on,  owing  to  the  slower  relaxation  of  the  fatigued 
muscle. 

It  is  evident  from  what  has  been  said  that  the  frequency  of 
stimulation  necessary  for  complete  tetanus  will  depend  upon  the 
rapidity  with  which  the  muscle  relaxes;  and  ever}i:hing  which 
diminishes  this  rapidity  will  lessen  the  necessary  frequency  of 
stimulation.  A  fatigued  muscle  may  be  tetanized  by  a  smaller 
number  of  stinmli  per  second  than  a  fresh  muscle,  and  a  cooled  by 
a  smaller  number  than  a  heated  muscle.  The  striped  muscles  of 
insects,  which  can  contract  a  million  times  in  an  hour,  require 
300  stimuli  per  second  for  complete  tetanus,  those  of  birds  100, 
of  man  40,  the  torpid  muscles  of  the  tortoise  only  3.  The  pale 
muscles  of  the  rabbit  need  20  to  40  excitations  a  second,  the  red 


732        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

muscles  only  lo  to  20 ;  the  tail  muscles  of  the  crayfish  40,  but  the 
muscles  of  the  claw  only  6  in  winter  and  20  in  summer.  The 
gastrocnemius  of  the  frog  requires  30  stimuli  a  second,  the  hyo- 
glossus  muscle  only  half  that  number  (Richet).  The  frequency  of 
stimulation  necessary  for  complete  tetanus  of  unstriped  muscle 
is  much  less  than  for  striped  muscle.  Smooth  tetanus  of  a  band  of 
muscle  from  the  frog's  stomach  was  obtained  with  strong  opening 
induction  shocks  at  the  rate  of  i  in  5  seconds. 

We  see,  then,  that  there  is  a  lower  limit  of  frequency  of  stimulation 
below  which  a  given  muscle  cannot  be  com-pletely  tetanized.  There 
appears  also  to  be  an  upper  limit  beyond  which  a  series  of  stimuli 
becomes  too  rapid  to  produce  complete  tetanus,  and  at  which  an  inter- 
rupted current  acts  like  a  constant  current,  causing  a  single  twitch  at 
its  commencement  or  at  its  end,  but  no  contraction  during  its  passage. 
This  limit  undoubtedly  does  not  depend  upon  the  frequency  of  stimula- 
tion alone ;  the  intensity  of  the  individual  excitations,  the  temperature 
of  the  muscle,  and  probably  other  factors,  affect  it.  For  Bernstein 
found  that  with  moderate  strength  of  stimulus  tetanus  failed  at  about 
250  per  second,  and  was  replaced  by  an  initial  contraction;  with  strong 
stimuli  at  more  than  1,700  per  second,  tetanus  could  still  be  obtained. 
Kronecker  and  Stirling,  stimulating  the  muscle  by  induced  currents  set 
up  in  a  coil  by  the  longitudinal  vibrations  of  a  magnetized  bar  of  iron, 
saw  tetanus  even  with  the  utmost  frequency  attainable,  4,000  shocks 
a  second,  according  to  Roth;  while  v.  Kries  in  a  cooled  muscle  found 
tetanus  replaced  by  the  simple  initial  twitch  at  100  stimuli  per  second, 
although  in  a  muscle  at  38°  C.  stimulation  of  ten  times  this  frequency 
still  caused  tetanus.  Recently  Einthoven,  exciting  the  nerve  of  a 
frog's  nerve-muscle  preparation  with  extremely  frequent  oscillatory 
condenser  discharges,  observed  tetanus  up  to  even  a  million  vibrations 
a  second,  if  the  current  intensity  was  at  the  same  time  very  greatly 
increased  (to  more  than  16,000  times  the  intensity  needed  with  a 
constant  current).  These  results  are  not  really  so  discordant  as  they 
appear;  for  it  is  known  that  with  electrical  stimulation  the  number  of 
excitations  is  not  necessarily  the  same  as  the  nominal  number  of  shocks. 
By  applying  a  telephone  to  a  muscle  excited  through  its  motor  nerve, 
it  has  been  shown  that  the  pitch  of  the  note  produced  by  the  tetanized 
muscle  corresponds  exactly  to  the  rate  of  excitation  up  to  a  certain 
frequency.  This  frequency  is  about  200  per  second  for  frog's  and 
about  1,000  per  second  for  mammalian  muscle  under  the  best  condi- 
tions. If  the  rate  of  excitation  is  still  further  increased,  there  is  no 
corresponding  increase  in  the  pitch.  Therefore,  some  of  the  stimuli 
are  now  producing  no  effect — '  falling  flat,'  so  to  speak  (Wedensky). 
One  reason  for  this  is  that  even  very  brief  currents  leave  alterations  of 
conductivity  and  excitability  behind  them  (Sewall),  which  we  shall 
have  to  discuss  in  another  chapter  (p.  759).     (See  also  p.  761.) 

It  is  only  while  the  actual  shortening  is  taking  place  that  a  tetanized 
muscle  can  do  external  work.  But,  although  during  the  maintenance 
of  the  contraction  no  work  is  done,  energy  is  nevertheless  being  ex- 
pended, for  the  metabolism  of  a  muscle  during  tetanus  is  greater  than 
during  rest,  and,  among  other  changes,  lactic  acid  is  produced.  There 
are  great  differences  in  the  ease  with  which  different  muscles  can  be 
exhausted  by  tetanus.  For  example,  the  muscles  which  close  the 
forceps  of  the  crayfish  or  lobster  have,  as  everyone  knows,  the  power 
of  most  obstinate  contraction.     Richet  tetanized  one  for  over  seventy 


MECHANICAL  PHENOtMENA  OF  MUSCULAR  CONTRACTION     733 

minutes,  and  another  for  an  hour  and  a  half,  before  exhaustion  came 
on,  while  a  tetanus  of  a  single  minute  exhausted  the  muscles  of  the 
crayfish's  tail.  The  gastrocnemius  of  a  summer  frog  kept  up  for  twelve 
minutes,  and  a  tortoise  muscle  for  forty  minutes. 

Continuous  stimulation  is  not  always  necessary  for  the  production 
of  continuous  contraction;  in  some  conditions  a  single  stimulus  is  suffi- 
cient. A  blow  with  a  hard  instrument  may  cause  a  dying  or  exhausted, 
and  in  thin  persons  even  a  fairly  normal,  musi  Ic  to  pass  into  long- 
continued  contraction.  This  so-called  '  idio-muscular  '  contraction 
seems  to  depend,  in  part  at  least,  on  the  great  intensity  of  the  stimulus. 
It  can  sometimes  be  obtained  in  the  frog's  gastrocnemius,  particularly 
in  spring  after  the  winter  fast.  It  is  not  a  tetanus  and  is  not  propa- 
gated along  the  muscular  fibres,  as  an  electrical  tetanus  is,  but  remains 
localized  at  the  spot  where  it  arises.  Similar  non-tetanic  contractions 
have  already  been  mentioned,  such  as  the  tonic  contraction  during  the 
passage  of  a  strong  voltaic  current  and  the  sustained  veratrine  contrac- 
tion. Ammonia  causes  also  a  long  but  non-tetanic  contraction,  and  this, 
too,  does  not  spread  when  the  substance  has  acted  only  on  a  portion 
of  the  muscle.  The  contraction  force  of  all  these  tonic  contractions, 
as  measured  by  the  resistance  necessary  to  overcome  or  prevent  them, 
is  less  than  the  contraction  force  in  electrical  tetanus  (Schenck). 

The  rate  at  which  the  wave  of  muscular  contraction  travels  may  be 
measured  by  stimulating  the  muscle  at  one  end,  and  recording,  by 
means  of  levers,  the  movements  of  two  points  of  its  surface  as  far 
apart  from  each  other  as  possible.  Time  is  marked  on  the  tracing  by 
means  of  a  tuning-fork,  and  the  distance  between  the  points  at  which 
the  two  curves  begin  to  rise  from  the  base-line  divided  by  the  time  gives 
the  velocity  of  the  wave.  Another  method  is  founded  upon  the  measure- 
ment of  the  rate  at  which  the  negative  variation  (p.  797)  passes  over 
the  muscle,  this  being  the  same  as  the  velocity  of  the  contraction-wave. 
In  frog's  muscle  it  is  about  three  metres  a  second,  or  six  miles  an  hour. 
Rise  of  temperature  increases,  fall  of  temperature  lessens  it.  When  a 
muscle  is  excited  through  its  nerve,  the  contraction  springs  up  first  of 
all  about  the  middle  of  each  muscular  fibre  where  the  nerve-fibre  enters 
it,  and  then  sweeps  out  in  both  directions  towards  the  ends.  But  so 
long  is  the  wave,  that  all  parts  of  the  fibre  are  at  the  same  time  involved 
in  some  phase  or  other  of  the  contraction. 

The  wave  of  contraction  in  unstriped  muscle  lasts  a  relatively  long 
time  at  any  given  point,  and  in  tubes  like  the  intestines  and  ureters, 
the  walls  of  which  are  largely  composed  of  smooth  muscle  arranged  in 
rings,  the  wave  shows  itself  as  a  gradually-advancing  constriction 
travelling  from  end  to  end  of  the  organ.  There  is  no  evidence  that 
the  contraction  of  smooth  muscular  fibres  is  discontinuous — that  is, 
composed  of  summated  contractions  like  a  tetanus ;  it  appears  to  be  a 
greatly-prolonged  simple  contraction.  An  artificial  stimulus,  mechani- 
cal or  electrical,  causes,  after  a  long  latent  period,  a  very  definitely- 
localized  contraction  in  a  rabbit's  ureter,  which  slowly  spreads  in  a 
peristaltic  wave  in  one  or  both  directions  along  the  muscular  tube. 
Here,  as  in  the  cardiac  muscle,  the  excitation  passes  from  fibre  to  fibre, 
while  in  striped  skeletal  muscle  only  the  fibres  excited  directly  or 
through  their  nerves  contract.  That  the  rhythmical  contraction  of 
the  heart  is  not  a  tetanus  has  already  been  seen.  It  is  a  simple  con- 
traction, intermediate  in  its  duration  and  other  characters  between  the 
twitch  of  voluntary  muscle  and  the  contraction  of  smooth  muscle.  The 
contraction  both  of  unstriped  and  of  cardiac  muscle  is  lengthened  and 
made  stronger  by  distension  of  the  viscera  in  whose  wails  they  occur, 
just  as  a  skeletal  muscle  contracts  more  powerfully  against  resistance. 


734        T^HE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Voluntary  Contraction. — There  is  evidence  that  the  voluntary 
contraction  is  a  tetanus.  One  of  the  strongest  buttresses  of  the 
theory  of  natural  tetanus  has  been  the  muscle-sound,  a  low  rumbling 
note  which  can  be  heard  by  listening  with  a  stethoscope  over  the 
contracting  biceps,  or,  when  all  is  still,  by  stopping  the  ears  with  the 
fingers  and  strongly  contracting  the  masseter  and  the  other  muscles 
concerned  in  closing  the  jaws.*  Discovered  about  ninety  years 
ago,  first  by  WoUaston  and  then  by  Erman,  half  a.  century  passed 
away  before  it  was  investigated  more  fully  by  Hclmholtz.  The 
latter  observer,  confirming  the  results  of  his  predecessors,  put  down 
the  pitch  of  the  sound  at  36  to  40  vibrations  per  second.  He  found, 
however,  that  little  vibrating  reeds  with  a  rate  of  oscillation  of  about 
19-5  per  second  were  more  affected  when  attached  to  muscle  thrown 
into  voluntary  contraction,  than  those  that  vibrated  at  a  smaller 
or  a  greater  rate.  He  therefore  concluded  that  the  fundamental 
tone  of  the  muscle  corresponded  to  this  frequency,  although,  since 
such  a  low  note  is  not  easily  appreciated,  the  sound  actually  heard 
was  really  its  octave  or  first  harmonic  (p.  304). 

The  objection  has  been  brought  forward  that  the  resonance  tone  of 
the  ear  also  corresponds  to  a  vibration  frequency  of  36  to  40  a  second. 
In  other  words,  this  is  the  natural  rate  of  swing  of  the  elastic  struc- 
tures in  the  middle  ear,  the  rate  they  will  most  easily  fall  into  if  set 
moving  by  an  irregular  mixture  of  faint,  low-pitched  tones  and  noises, 
and  not  compelled  to  vibrate  at  some  other  rate  by  a  distinct  sound 
of  definite  pitch.  Now,  this  resonance  tone  might  be  elicited  by  a 
quivering  muscle  if,  among  many  diverse  rates  of  oscillation  of  different 
portions  of  its  substance,  the  rate  of  36  to  40  a  second  anywhere  ap- 
peared, and  the  note  corresponding  to  the  real  rate  of  vibration  of  the 
muscle  as  a  whole  might  be  overpowered.  Or,  even  if  there  were  no 
regular  rate  of  vibration  of  the  whole  muscle,  but,  instead,  a  series  of 
irregular  tremors  or  pulls  due  to  irregularities  in  the  contraction,  con- 
nected with  a  want  of  co-ordination  of  all  the  fibres  (Haycraft),  the  ear 
might  from  time  to  time  pick  out  of  the  turmoil  of  feeble  aerial  waves 
those  corresponding  to  its  resonance  tone,  just  as  a  tuning-fork  or  a 
piano-string  attuned  to  a  particular  note  would  catch  it  up  amid  a 
thousand  other  sounds  and  strengthen  it. 

But  while  this  renders  it  highly  probable  that  the  resonance  of  the 
ear  contributes  to  the  production  of  the  muscle-sound,  and  shows  that 
we  cannot  from  the  pitch  of  the  muscle-sound  alone  deduce  the  rate 
at  which  the  muscle-substance  is  vibrating,  it  does  not  invalidate 
Helmholtz's  objective  observations  with  the  oscillating  reeds. 

And  several  observers  (Schafer,  Horsley,  v.  Kries)  have  noticed 
periodic  oscillations,  at  the  rate  of  10  or  12  per  second,  in  the 
curves  taken  from  muscles  (Fig.  261),  contracted  voluntarily 
against  a  small  resistance.  When  the  resistance  is  greater,  the 
rate  may  be  as  much  as  18  or  20  a  second,  and  in  quick  and  rapidly 

•  In  order  that  a  muscular  sound  may  be  produced  there  must  be  a  certain 
abruptness  in  the  contraction.  Thus,  the  slowly-contracting  smooth  muscles 
do  not  produce  a  sound,  aor  the  slowly-contracting  heart-muscle  of  cold- 
blooded animals. 


MECHANICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     735 

repeated  movements  ctf  the  fingers  even  40  a  second.  In  habitual 
movements,  such  as  those  employed  by  a  man  in  his  trade,  the 
tremors  are  much  less  coarse  than  in  unaccustomed  movements. 
For  this  reason  the  tremors  of  the  left  hand  are  greater  than  those 
of  the  right  in  executing  a  movement  usually  made  with  the  latter 
(Eshner).  In  disease  these  tremors  are  often  increased — e.g.,  in 
the  clonic  convulsions  of  epilepsy — but  the  frequency  is  the  same. 


MA#l/^WlM 


Fig.  a6i. 


-Vibrations  of  Contracted  Arm  Muscles  (Griffiths).     The  arm  was  stretched 
out,  holding  a  weight  of  about  6  kilos. 


Similar  vibrations,  and  at  about  the  same  rate,  are  seen  in  curves 
traced  by  muscles  excited  through  stimulation  of  the  motor  areas 
of  the  surface  of  the  brain.  Since  this  rate  remains  the  same  whether 
the  motor  cortex,  the  corona  radiata,  or  the  spinal  cord  is  excited, 
and,  unlike  the  rate  of  response  to  excitation  of  peripheral  nerves, 
is  independent  of  the  frequency  of  stimulation  (so  long  as  the  rate 
of  stimulation  is  greater  than  10  or  12  a  second),  it  has  been  supposed 
to  represent  the 
rhythm  with  which 
impulses  are  dis- 
charged from  the 
motor  cells  of  the  cord 
(Fig.  262).  It  is  prob- 
able that  the  cortical 
centres  discharge  at 
about  the  same  rate, 
for  not  only  is  it  im- 
possible to  articulate 
more  rapidly  than 
eleven  syllables  per 
second,  but  it  is  impossible  to  reproduce  the  act  of  articulation  in 
thought  at  a  greater  rate  than  this  (Richet).  But  while  this  rate 
of  10  or  12  a  second  does  seem  to  represent  a  fundamental  rhythm 
of  the  central  discharge,  there  are  facts  which  indicate  that  upon 
this  relatively  slow  rhythm  a  quicker  rhythm  is  superposed.  la 
other  words,  each  of  these  discharges  is  itself  discontinuous,  and 
made  up  of  a  number  of  separate  impulses. 


Fig.  262. — Contractions  caused  by  Stimulation  of  tlie 
Spinal  Cord. 


736        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Thus,  according  to  Piper,  the  total  number  of  simple  discharges, 
each  associated  with  an  electrical  change  in  the  muscle,  as  recorded  by 
the  string  galvanometer,  is  47  to  50  a  second.  The  rhythm  of  strych- 
nine tetanus  in  the  frog  is  about  8  to  12  per  second.  By  means  of  the 
capillary  electrometer  (p.  702)  large  electrical  oscillations  at  this  rate 
can  be  demonstrated,  each  of  which  represents  a  short  tetanic  spasm, 
as  is  shown  by  the  fact  that  a  number  of  smaller  electrical  oscillations 
are  superposed  upon  the  large  ones  (Sanderson).  The  electrical  changes 
suggest  that  each  discharge  causes  a  simple  contraction  much  more 
prolonged  than  the  twitch  of  a  directly  stimulated  muscle.  This 
removes  the  difificulty  of  understanding  how  such  a  small  number  as 
10  contractions  per  second  could  be  smoothly  fused,  and  indicates  that 
even  the  shortest  possible  voluntary  movement,  which  can  be  executed 
in  ^  to  ^  of  a  second,  is  not  caused  by  a  single  impulse,  but  is  a 
tetanus.  For  these  brief  movements  the  frequency  of  oscillation,  as 
shown  by  the  action  currents,  is  the  same  as  for  sustained  contractions. 
The  electrical  changes  in  the  voluntarily  contracted  muscle  seem  to 
differ  in  amplitude  or  abruptness  from  those  produced  in  experimental 
tetanus.  For  secondary  tetanus  (p.  806)  is  not  caused  by  muscle  in 
voluntary  contraction.  But  this  is  also  the  case  with  the  other  pro- 
longed contractions  caused  by  continuous  artificial  stimulation — e.g., 
Ritter's  tetanus  (p.  715)  and  the  contraction  produced  by  sodium 
chloride  or  ammonia.  We  need  not  hesitate  to  conclude,  then,  that 
the  voluntary  contraction  is  discontinuous,  in  the  sense  that  it  is  not 
a  perfectly  smooth  and  uniform  tonic  contraction,  although  we  still 
lack  a  decisive  proof  that  it  is  maintained  by  a  strictly  intermittent 
outflow  of  nervous  energy,  and  not  by  a  continuous  outflow  causing  a 
sustained  contraction,  which,  it  may  be,  remits  and  is  reinforced  at 
intervals.  The  apparent  discrepancies  as  to  the  rate  of  discharge  in 
the  results  obtained  by  different  observers,  and  by  different  methods, 
far  from  exciting  distrust  of  them  all,  really  lend  support  to  the  idea 
of  a  fundamental  and  fairly  constant  rhythm  in  the  outflow  as  soon 
as  it  is  recognized  that  the  higher  rates  are  approximately  multiples 
of  the  lower.  Thus,  the  number  deduced  by  Helmholtz  from  the  ex- 
periment of  the  springs  is  twice  the  lowest  rate  calculated  from  graphic 
records  of  the  contraction.  The  rates  corresponding  to  the  muscle- 
sound  and  to  the  frequency  of  the  electrical  oscillations  are  about  four 
times  this  number.  Now,  in  a  vibrating  elastic  body  like  a  contracting 
muscle,  a  simple  mathematical  relation  of  this  sort  might  be  expected 
to  appear  when  determinations  of  the  rate  of  oscillation  and  of  accom- 
panying periodic  changes  are  made  by  methods  varying  in  principle  and 
in  delicacy.  For  instance,  an  arrangement  suited  to  record  and  to 
count  coarse  vibrations  could  not  be  expected  to  give  the  same  result 
as  an  arrangement  suited  to  record  and  count  fine  vibrations.  But  if 
both  the  coarse  and  the  fine  vibrations  were  related  to  a  fundamental 
rhythm,  a  simple  proportion  might  be  expected  to  exist  between  the 
two  sets  of  results. 

(3)  Thermal  Phenomena  and  Transformation  of  Energy  in  the 
Muscular  Contraction. — When  a  muscle  contracts,  its  temperature 
rises;  the  production  of  heat  in  it  is  increased.  This  is  most  dis- 
tinct when  the  muscle  is  tetanized,  but  has  also  been  proved  for 
single  contractions.  The  change  of  temperature  can  be  detected 
by  a  delicate  mercury  or  air  thermometer;  and,  indeed,  a  ther- 
mometer thrust  among  the  thigh-muscles  of  a  dog  may  rise  as  much 


THERMAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    737 


as  1°  to  2°  C.  when  the  muscles  are  thrown  into  tetanus.  In  the 
isolated  muscles  of  cold-blooded  animals  the  increase  of  tempera- 
ture is  much  less;  and  thermo-elcctrical  methods,  which  are  the 
most  delicate  at  present  known,  have  generally  been  used  for  its 
detection  and  measurement. 

They  depend  upon  the  fundamental  fact  of  thermo-electricity,  that 
in  a  circuit  composed  of  two  metals  a  current  is  set  up  if  the  junctions 
of  the  metals  are  at  different  tempera- 
tures. 

Where  no  very  fine  differences  of 
temperature  are  to  be  measured,  a  single 
thermo-j  unction  of  German  silver  and 
iron,  or  copper  and  iron,  is  inserted  into 
a  muscle  or  between  two  muscles.  But 
the  electromotive  force,  and  therefore 
the  strength  of  the  thermo-electric  cur- 
rent, is  proportional  for  any  given  pair 
of  metals  to  the  number  of  junctions, 
and  for  delicate  measurements  it  may 
be  necessary  to  use  several  connected 
together  in  series.  A  thermopile  of 
antimony- bismuth  junctions  gives  a 
stronger  current  for  a  given  difference  of 
temperature  than  the  same  number  of 
German  silver-iron  couples,  but  from  its 
brittle  nature  is  otherwise  less  convenient . 

The  direction  of  the  current  in  the  cir- 
cuit is  such  that  it  passes  through  the 
heated  junction  from  bismuth  to  anti- 
mony and  from  copper  or  German  silver 
to  iron.  Knowing  this  direction,  we  are 
aware  of  the  changes  of  temperature 
which  take  place  from  the  movements 
of  the  mirror  of  the  galvanometer  with 
which  the  pile  is  connected.  In  the 
thermopiles  employed  in  the  recent  ex- 
tensive investigations  of  Hill  the  alloy 
constantan  is  coupled  with  iron,  the 
electromotive  force  of  this  combination 
being  exceptionally  great. 

The  muscle  which  is  to  be  excited  is 
brought  into  close  contact  with  one 
junction  or  set  of  junctions,  the  other 
set  being  kept  at  constant  temperature. 
The  image  will  now  come  to  rest  on  the 
scale;  and  excitation  of  the  muscle  will 
cause  a  movement  indicating  an  increase 
of  temperature  in  it,  the  amount  of  which 
can  be  calculated  from  the  deflection.  In 
one  form  (Fig.  263)  the  thermopile  con- 
stitutes a  hollow  cone,  in  which  a  muscle  can  be  arranged  so  as  to  eliminate 
largely  the  errors  due  to  differences  of  temperature  of  the  muscle,  or  to 
the  "slip  "  of  the  contracting  muscle  over  the  junctions. 

In  this  way  Helniholtz  observed  a  rise  of  temperature  of  0-14°  to 
0  '18°  C.  in  excised  frogs'  muscles  when  tetanizcd  for  a  couple  of  minutes . 

47 


5 

Fig.  263.  —  Conical  Thermopile 
containing  Gastrocnemius  Mus- 
cle Reversed.  C,  copper  leads 
to  galvanometer;  S,  stimulating 
wire.  The  straight  lines  indicate 
iron,  the  crossed  lines  constan- 
tan, the  e.xternal  junctions  em- 
bedded in  the  ebonite  frame 
being  at  a,  the  internal  junc- 
tions, b,  in  contact  with  the 
muscle. 


738       THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Heidenhain,  with  a  very  delicate  pile,  found  a  rise  of  0001°  to 
0-005°  C.  for  a  single  contraction  of  a  frog's  muscle.  On  the  assump- 
tion that  the  pile  had  time  to  take  on  the  temperature  of  the 
muscle  before  there  was  any  appreciable  loss  of  heat,  this  would 
be  equal  to  the  production  by  every  gramme  of  muscle  of  a  thou- 
sandth to  five-thousandths  of  a  gramme-calorie  (p.  653)  of  heat. 
From  Pick's  observations  we  may  take  about  three-thousandths 
of  a  gramme-calorie  as  the  maximum  production  of  a  gramme  of 
frog's  muscle  in  a  single  contraction. 

Hill  has  shown  that  in  the  case  of  the  single  contraction  or  twitch 
the  evolution  of  heat  may  be  so  rapid  as  to  be  practically  instan- 
taneous, indicating  that  it  depends  upon  some  sudden  '  explosive  ' 
chemical  reaction;  or,  on  the  other  hand,  under  certain  conditions 

it  may  last  as  long  as  two 
seconds — that  is,  from  four 
to  ten  times  as  long  as  the 
contraction  itself.  In  the 
absence  of  oxygen,  when 
the  muscle  is  left,  for  in- 
stance, in  an  atmosphere  of 
hydrogen,  the  heat  produc- 
tion becomes  markedly  pro- 
longed. When  abundant 
oxygen  is  supplied,  the  dura- 
tion of  the  discharge  of  heat 
is  decreased.  In  a  tetanus 
the  evolution  of  heat  lags 
behind  the  excitation,  and 
the  discharge  associated 
with  each  stimulus  is  not 
complete  till  0-5  to  2*5 
seconds  after  the  stimulus.  In  a  prolonged  complete  tetanus 
the  heat  production  corresponding  to  the  first  tenth  of  a  second 
of  excitation  is  far  greater  than  that  corresponding  to  the  second 
tenth  of  a  second,  and  so  on,  until  eventually  a  uniform  dis- 
charge of  heat,  at  a  rate  much  smaller  than  the  initial  rate,  is 
reached.  When  frogs'  muscles  are  rapidly  stimulated  indirectly 
(through  the  nerves)  till  fatigue  has  occurred,  the  maximum  value 
of  the  heat  evolved  approximates  to  09  gramme  -  calorie  per 
gramme  of  muscle,  about  70  or  80  per  cent,  being  hberated  in  the 
first  two  minutes  (Peters). 

A  fact  of  great  significance  in  regard  to  the  relation  of  the  reaction 
upon  which  the  heat  production  depends  and  the  mechanical 
conditions  in  the  active  muscle  is  that  the  production  of  heat  is 
determined  by  the  length  of  muscular  fibres  existing  at  the  time 
when  the  heat  is  being  evolved.  From  this  it  has  been  assumed 
that  the  production  of  heat  in  active  muscle  is  a  surface  effect,  and 


Fig.  264. — A,  a  single  copper-iron  thermo- 
electric couple ;  B.two  pairs,  one  inserted  into 
the  tissue  6,  the  other  dipping  into  water  in  a 
beaker  a.  The  temperature  of  the  water 
may  be  adjusted  so  that  the  galvanometer 
shows  no  deflection.  The  temperature  of  the 
tissue  is  then  the  same  as  that  of  the  water. 


THERMAL  PHENOMENA  OF  MUSCULAR  CONTRACTION         739 

not  an  effect  taking  place  uniformly  throughout  the  muscle  substance 
and  related  accordingly  to  tlie  volume  or  mass  of  the  muscular 
substance  (Blix).  Much  evidence  has  been  accumulated  in  favour 
of  this  hypothesis.  For  example,  a  muscle  contracting  isometrically 
(p.  721)  produces  more  heat  the  greater  is  the  initial  tension  (the 
more  it  is  stretched  at  the  begining  of  the  excitation) — that  is, 
the  greater  its  length  during  contraction  (Heidenhain).  When  a 
muscle  is  allowed  to  shorten  in  a  tetanus,  the  heat  production  as 
compared  with  that  of  an  isometric  contraction  of  the  same  dura- 
tion, and  evoked  by  the  same  strength  of  stimulus,  is  diminished 
by  as  much  as  40  per  cent. 

Relation  between  the  Development  of  Mechanical  Energy  and 
Heat  Production  in  Active  Muscle.— There  is  no  simple  relation 
between  the  external  work  done  in  a  muscle  twitch  and  the  heat 
set  free.  The  efficiency  of  the  muscular  machine,  as  estimated 
by  the  proportion  of  the  work  done  to  the  total  energy  degraded, 
varies  with  a  number  of  factors — e.g.,  the  load,  the  number  of  fibres 
excited,  and  the  intensity  of  the  excitation  of  each  fibre,  the  two 
latter  factors  depending  upon  the  strength  of  the  stimulus. 

The  greater  the  resistance,  so  long  as  the  muscle  can  overcome 
it  so  as  to  do  its  utmost  amount  of  external  work,*  the  larger  is 
the  proportion  of  energy  which  appears  as  work,  the  smaller  the 
proportion  which  appears  as  heat.  For  every  muscle,  under  given 
conditions,  there  is  a  certain  load  which  can  be  raised  more  advan- 
tageously than  any  other;  but  even  in  the  most  favourable  case, 
an  excised  frog's  muscle  never  does  work  equal  to  more  than  J  of 
the  heat  given  off.  Generally  the  ratio  is  much  less,  and  may  sink 
as  low  as  -^-g.  In  the  intact  mammalian  body  the  muscles  work 
somewhat  more  economically  than  the  excised  frog's  muscles  at 
their  best;  for  both  experiment  and  calculation  show  (p.  662) 
that  in  a  normal  man  under  the  most  favourable  conditions  as 
much  as  1  of  the  energy  is  converted  into  work.  According  to 
Zuntz  and  Katzenstein,  35  per  cent,  of  the  total  energy  appeared 
as  muscular  work  in  chmbing  a  mountain,  and  in  bicycling  only 
25  per  cent.  Movements  which  have  been  much  practised  are 
more  economically  performed  than  unaccustomed  ones,  and  this 
explains  the  superior  efficiency  of  the  muscles  concerned  in  climbing, 
for  no  movements  can  possibly  be  more  familiar  than  those  con- 
cerned in  locomotion.  So  far  as  this  indication  goes,  it  would  seem 
that  in  the  treatment  of  obesity  unfamiliar,  and  therefore  physio- 
logically expensive,  forms  of  exercise  should  be  recommended,  in 
so  far,  of  course,  as  they  do  not  injuriously  react  irpon  the  general 
condition,  especially  upon  the  circulation. 

♦  This  statement,  baswl  on  experiments  \v«th  excised  frog's  muscles,  is  not, 
of  course,  inconsistent  with  the  fact  mentioued  on  p.  662,  that  in  the  intact 
body  the  fraction  ofJiie  energy  transktrmed  into  beat  is  greater  in  hard  than 
in  moderate  work. 


740        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

4 

When  a  muscle,  excited  by  maximal  stimuli,  is  made  to  lift  con- 
tinuously increasing  weights,  both  the  woik  done  and  the  heat  given 
out  increase  up  to  a  certain  limit.  The  muscle,  as  it  were,  burns  the 
candle  at  both  ends.  The  heat-production  reaches  its  maximum  some- 
whr.t  sooner  than  the  work. 

It  is  certain  that  when  work  is  done  by  a  muscle  an  equivalent 
amount  is  subtracted  from  its  sum-total  of  energy,  and  imder  proper 
conditions  this  can  be  actually  demonstrated  by  the  deficiency  in  the 
heat-production.  This  is  done  by  means  of  a  contrivance  called  a 
work-adder.  It  consists  of  a  wheel,  the  rotition  of  which  raises  a 
weight  attached  to  a  cord  wound  round  its  axle.  The  muscle  acts  on 
the  periphery  of  the  wheel,  and  by  rotating  it  raises  tlic  weight  a  little 
at  each  contraction.  At  the  end  of  the  contraction  the  wheel  is  pre- 
vented from  moving  back  by  a  catch.  The  work  done  in  a  series  of 
contractions  is  calculated  from  the  total  height  to  which  the  weight 
has  been  raised.  Suppose  a  frog's  gastrocnemius  is  maae  to  contract 
a  certain  number  of  times  while  attached  tg  the  work-adder,  and  that 
simultaneously  the  heat-production  is  measured  by  means  of  a  thermo- 
pile. Let  H  represent  the  heat  actually  produced,  and  h  the  heat 
equivalent  of  the  work  done.  Now  let  the  muscle  be  disconnected  from 
the  adder  and  made  to  raise  the  same  weight,  directly  attached  to  it, 
by  a  series  of  contractions  elicited  in  precisely  the  same  way  as  the 
previous  ones,  except  that  the  weight  is  allowed  to  fall  with  the  muscle 
when  it  relaxes  after  each  contraction.  Here  heat  corresponding  to  the 
external  work  disappears  from  the  muscle  during  the  contraction  just 
as  in  the  first  experiment,  but  this  heat  is  returned  to  the  muscle  during 
the  relaxation,  since  on  the  whole  no  external  work  is  done.  The  heat 
produced  in  the  second  experiment  is  found,  as  a  matter  of  fact, 
allowing  for  unavoidable  errors,  to  be  equal  to  H  +  h. 

According  to  Hill,  the  true  '  efficiency  '  of  the  muscle  is  not  the 
r  itio  W/H.  where  W  is  the  external  work  and  H  the  total  heat  liberated, 
bat  T/H  where  T  is  the  maximum  increase  of  tension  set  up  during  the 
t  A^itch  wh^n  the  muscle  is  contracting  isometrically.  This  fraction  T/H 
IS  constant  whatever  be  the  initial  tension,  the  number  of  fibres  excited, 
or  the  strength  of  excitation  of  each  fibre.  For  the  theory  of  the 
muscular  contraction  the  tension  auring  an  isometric  muscle  twitch, 
which  represents  the  potential  energy  suddenly  developed  in  conse- 
quence of  the  excitation,  is  accordingly  much  more  important  than  the 
height  of  the  contraction,  which  is  related  to  the  worK  actually  done. 
The  essential  thing  in  muscular  contraction  may  be  the  abrupt  develop- 
ment of  this  tension  through  a  chemical  reaction  which  liberates  certain 
substances  at  some  membrane  or  surface  in  the  muscle.  The  potential 
energy  once  in  being  may  or  may  not  be  transformed  into  work,  and  if 
so  transformed  the  change  may  be  accomplished  economically  or  waste- 
fully,  according  to  the  conditions  of  the  contraction.  The  ratio  T/H 
decreases  in  fatigue,  and  witli  the  time  during  which  the  muscle  has 
been  deprived  of  its  blood-supply.  Hill  has  calculated  the  absolute 
value  of  the  heat-production  in  tetanus  of  a  eartorius  or  semimcm* 
branosus  muscle  of  the  frog.  This  quant  ty,  reckoned  per  centimetre 
of  length  of  the  muscle,  per  gramme  weight  of  the  tension  developed 
and  per  second  of  maintenance  of  the  tension,  is  relatively  constant  at 
a'xiut  0-000015  gramme-calorie.  Including  the  recovery  processes  of 
oxidation  following  the  contraction  the  total  heat-production  would 
amount  to  about  0-000025  calorie.  The  potential  energy  possessed  by 
a  muscle  of  a  length  of  a  centimetre  when  maintaining  a  tension  of  a 
gramme  is  abo\it  0*000004  calorie.  So  that  to  maintain  this  state  of 
potential  energy  six  or  seven  times  as  much  energy  must  be  liberated 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     741 

per  second.  The  maintenance  of  prolonged  tension  is,  therefore,  from 
the  point  of  view  of  the  mechanical  result,  an  exceedingly  wasteful 
process,  with  a  very  low  efficiency  in  comparison  with  the  high  efficiency 
in  a  lapid  twitch.  This  enables  u^.  to  sec  how  important  a  part  in  heat- 
production,  and  therefore  in  temperature  regulation,  the  tonus  of  muscle 
and  the  prolonged  contractions  of  shivering  may  possess  (p.  670). 

We  are  as  yet  in  the  dark  as  to  the  precise  relation  of  the  energy 
which  appears  as  heat  and  of  that  which  is  converted  into  work. 
The  ultimate  source  of  both  is,  of  course,  the  oxidation  (and 
cleavage)  of  the  food  substances.  It  was  at  one  time  a  favourite 
theory  that  in  a  muscle,  as  in  a  heat-engine,  the  chemical  energy 
is  first  converted  into  heat,  and  part  of  the  heat  then  transformed 
into  work.  There  is  no  evidence  that  this  is  the  case.  It  is, 
indeed,  impossible  that  such  differences  of  temperature  can  exist 
as  would  be  compatible  with  the  known  efficiency  of  the  muscular 
machine.  Hypotheses  based  on  the  assumption  that  the  chemical 
energy  is  immediately  changed  into  work,  perhaps  through  the  pro- 
duction of  surface  effects,  have  met  with  increasing  favour,  but 
data  are  as  yet  too  few  for  the  formulation  of  any  really  satisfactory 
theory.  The  close  relation  between  the  heat-production  and  the 
formation  of  lactic  acid  in  contraction  which  have  been  shown  to 
exist,  is  a  suggestive  fact  whose  full  significance  will  only  be  revealed 
by  further  investigation.  The  restitution  processes  by  which  the 
original  state  of  the  muscle  is  restored  after  contraction  are,  of 
course,  intimately  related  to  those  concerned  in  the  actual  shorten- 
ing; but  unless  we  know  how,  and  in  consequence  of  what  chemical 
or  physical  changes,  the  equilibrium  of  the  resting  muscle  has  been 
disturbed,  we  cannot  know  how,  or  in  consequence  of  what  chemical 
or  physical  changes,  it  is  restored. 

Section  IV. — Chemical  Phenomena  of  the  Muscular 
Contraction. 

The  composition  oj  dead  mammalian  muscle  of  the  striped  variety  may 
be  stated,   in   round  numbers,  as  follows,   but  there  are  considerable 
variations,  even  within  the  same  species : 

Water        ---.._,         .75  per  cent. 
Proteins     --------     20        ,, 

Fats,  lecithin,  and  chole.sterin    -         -         -         -       2         ,, 

Nitrogenous  extractives,  kreatin,  carnosin,  phos- ' 

pho-carnic  acid,   inosinic  acid,   purin  bodies, 

such  as  uric  acid,  hypoxanthin,  xanthin,  etc.  - 
Carbo-hydrates  (glycogen,  dextrose,  maltose)  - 
Non-nitrogenous  organic  substances  (lactic  acid, 

inosit)  ---_..- 

Pigment  (myohaematin  or  myochrome,  a  haemoglobin  not  precisely 

identical  with  that  of  blood). 
Inorganic  substances  less  than  i  per  cent,  (chlorides,  carbonates, 

phospliates,  and  sulphates  of  potassium,  sodium,  iron,  calcium, 

magnesium).    Potassium  is  absent  from  the  nuclei  (Frontispiece) 


742        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Of  the  nitrogenous  extractives,  kreatin  (p.  587)  and  carnosin  are 
present  in  greatest  quantity,  muscle  containing  0*2  to  0-4  per  cent,  of 
kreatin.  Carnosin  (C9H14N4O3)  is  a  substance  with  basic  properties, 
and  can  be  spUt  up  into  histidin  and  /8-amino-propionic  acid,  an 
amino-acid  not  identical  with  alanin  (or  «-amino-propionic  acid),  but 
having  the  NH2  coupled  to  the  ^i  instead  of  the  a  carbon  atom  (p.  55 7I. 

There  is  more  water  in  the  muscles  of  young  than  of  old  animals 
(v.  Bibra),  and  more  in  tetanized  than  in  rested  muscle  (Ranke).  The 
fats  are  variable  in  amount,  and  belong  to  a  small  extent  to  the  actual 
muscle-fibres.  For  even  when  the  visible  fat  is  separated  with  the 
utmost  care,  nearly  i  per  cent,  of  fat  still  remains  (Steil). 

The  glycogen  content  varies  extremely  in  different  muscles  and  in 
the  same  muscle  under  different  nutritive  and  functional  conditions. 
Thus,  in  one  and  the  same  dog  the  biceps  brachii  contained  0'i7  and 
the  quadriceps  femoris  0*53  per  cent.  In  dogs  on  a  diet  rich  in  carbo- 
hydrate and  protein  the  percentage  in  the  whole  skeletal  musculature 
ranged  from  0*7  to  3*7,  and  in  the  heart  from  o*i  to  1-2.  The  average 
for  human  muscles  has  been  given  as  0*4  per  cent.  In  lean  horse-flesh 
Pfliiger  found  0*35  per  cent,  of  glycogen,  but  no  sugar.  The  total 
nitrogen  was  3-21  per  cent,  of  the  moist  tissue.  .-J'he  lactic  acid  of 
muscle  and  other  tissues  is  the  (^-lactic  acid,  which  rotates  the  plane  of 
polarization  to  the  right.  By  the  action  of  certain  bacteria  on  cane- 
sugar  /-lactic  acid  is  obtained,  which  is  left  rotatory.  The  optically 
inactive  fermentation  lactic  acid  is  obtained  by  the  fermentation  of 
lactose. 

Smooth  muscle  is  somewhat  richer  in  water  than  the  striated  variety 
from  the  same  species,  because  skeletal  muscle  is  richer  in  fat.  Glycogen 
is  either  absent  or  present  only  in  traces  in  the  smooth  muscle  (of  the 
stomach  and  bladder).  Lactic  acid,  kreatin,  and  kreatinin  are  also 
found  in  much  smaller  amount  than  in  striped  muscle  (Mendel  and  Saiki). 
As  in  striated  muscle,  hypoxanthin  is  the  conspicuous  purin  base 
occurring  in  the  free  form — i.e.,  obtainable  in  muscle  extracts.  The 
most  remarkable  difference  in  the  quantitative  relations  of  the  inorganic 
constituents  is  that  in  striated  muscle  potassium  preponderates  over 
sodium  and  magnesium  over  calcium,  whereas  in  the  smooth  variety 
this  relation  is  reversed. 

It  would  be  natural  to  expect  that  the  proteins,  which  bulk  so 
largely  among  the  solids  of  the  dead  muscle,  and  which  are  so  obvi- 
ously important  in  the  living  muscle,  should  be  affected  by  contrac- 
tion. But  up  to  the  present  time  no  quantitative  difference  in  the 
proteins  of  resting  and  exhausted  muscle  has  ever  been  made  out. 
The  quantity  of  kreatin  (and  kreatinin)  is  said  by  some  authorities 
to  be  increased.  The  following  chemical  changes  have  been  defi- 
nitely established.     In  an  active  muscle — 

(a)  More  carbon  dioxide  is  produced,  [b)  More  oxygen  is  consumed, 
(c)  Lactic  acid  is  formed,  {d)  Glycogen  is  used  up.  {e)  The  substances 
soluble  in  water  diminish  in  amount;  those  soluble  in  alcohol  increase. 

Production  of  Carbon  Dioxide  and  Consumption  of  Oxygen  during 
Contraction. — This  subject  has  already  been  dealt  with  in  part  in 
connection  with  tissue  respiration  (p.  265).  The  fact  that  muscular 
exercise  increases  the  carbon  dioxide  output  and  the  oxygen  absorp- 
tion at  the  pulmonary  surface,  shows  that  oxidation  processes 
involving  ultimately  the  combustion  of  carbon-containing  substances 


CHEMICAL  PHESOMENA  OF  MUSCULAR  CONTRACTION    743 

are  associated  with  the  activity  of  the  muscular  tissue,  but  does 
not  of  itself  prove  that  the  final  steps  of  the  oxidation  occur  in  the 
muscles  themselves.  This  has  been  demonstrated,  however,  by 
observations  on  isolated  muscles.  When  well  supplied  with 
oxygen,  these,  in  addition  to  the  stock  of  carbon  dioxide  in  solution, 
in  the  form  of  carbonates  and  in  other  combinations,  which  they 
possess  at  the  moment  of  isolation,  continue  to  produce  carbon 
dioxide,  and  this  production  is  markedly  increased  by  stimulation. 
The  best  evidence  is  to  the  effect  that  only  preformed  carbon  dioxide 
is  given  off  by  isolated  muscles  in  the  absence  of  oxygen.  They 
can  go  on  contracting  indeed,  as  previously  stated,  in  an  atmosphere 
of  hydrogen  or  nitrogen,  and  may  seem  to  be  producing  carbon 
dioxide,  but  the  increased  output  appears  to  be  due  simply  to  an 
accelerated  decomposition  of  already  existing  carbonates,  or  perhaps 
other  combinations  in  which  carbonic  acid  is  loosely  held,  brought 
about  by  lactic  acid,  which  in  the  absence  of  oxygen,  is  not  trans- 
formed as  it  is  under  normal  conditions,  and  accumulates  in  the 
muscular  substance,  uniting  with  bases,  and  thus  displacing 
carbonic  acid. 

Formation  of  Lactic  Acid — Reaction  of  Muscle. — To  litmus-paper 
fresh  muscle  is  amphicroic — that  is,  it  turns  red  litmus  blue  and  blue 
litmus  red.  This  is  due,  partly  at  least,  to  the  phosphates.  Mono- 
phosphate (tribasic  phosphoric  acid,  H3PO4,  in  which  one  hydrogen 
atom  is  replaced,  say,  by  sodium  or  pot-assium)  reddens  blue  litmus, 
while  diphosphate  (where  two  hydrogen  atoms  are  replaced)  turns  red 
litmus  blue.  Litmoid  (lacmoid)  differs  from  litmus  in  not  being  affected 
by  monophosphates.  Diphosphates  turn  red  litmoid  blue,  and  so  does 
fresh  muscle,  which  has  no  effect  on  blue  litmoid.  A  cross-section 
of  fresh  muscle  is  about  neutral  (sometimes  faintly  acid)  to  turmeric 
paper,  which  is  turned  yellow  by  monophosphates.  A  muscle  which 
has  entered  into  rigor  or  has  been  fat\gued  by  prolonged  stimulation  is 
distinctly  acid  to  blue  litmus  and  to  brown  turmeric,  reddening  the 
former  and  turning  the  latter  yellow,  but  does  not  affect  blue  litmoid. 

Perfectly  fresh  resting  muscle  excised  with  avoidance  of  all  un- 
necessary manipulation  contains  very  little  lactic  acid  (as  little  as 
002  per  cent,  expressed  as  zinc  lactate).  Mechanical  injury, 
heating,  and  chemical  irritation  cause  a  marked  increase  in  the 
amount.  Under  anaerobic  conditions — ^in  an  atmosphere  of 
hydrogen,  for  instance — lactic  acid  is  spontaneously  developed  in 
the  resting  muscle  so  long  as  irritability  persists,  but  not  longer. 
In  air,  which  for  even  small  excised  muscles  corresponds  to  a  partial 
asphyxia,  there  is  a  small  increase  in  the  lactic  acid,  but  its  pro- 
duction is  very  slow  in  comparison  with  that  in  the  hydrogen 
atmosphere.  In  pure  oxygen  not  only  is  there  no  accumulation 
of  lactic  acid  for  a  long  time  after  excision,  but  a  portion  of  the 
amount  originally  present  in  the  resting  excised  muscle  disappears. 
The  same  is  true  of  the  lactic  acid  formed  in  a  muscle  fatigued  by 
stimulation  when  it  is  afterwards  placed  in  an  atmosphere  of  pure 


744        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

oxygen.  There  is  no  doubt  that  the  production  of  lactic  acid  in 
functional  activity  and  its  transformation  into  other  substances 
are  processes  that  go  on  also  in  the  muscles  of  the  intact  body. 
The  formation  of  the  acid  in  the  excised  muscle,  far  from  being  a 
sign  of  death,  is  an  index  of  the  '  survival  '  of  a  process  by  which 
it  is  normahy  formed,  as  the  accumulation  of  it  is  an  index  of  the 
crippling,  in  the  absence  of  oxygen,  of  a  mechanism  by  which  it  is 
normally  transformed. 

The  lactic  acid  which  accumulates  in  the  excised  muscle  in  rigor 
and  activity  does  not  remain  free,  since  blue  litmoid  paper  is  not 
reddened  as  it  would  be  by  free  lactic  acid.  It  causes  a  repartition 
of  the  bases  at  the  expense  of  the  sodium  carbonate  and  disodium 
phosphate,  the  latter  being  changed  into  monophosphate,  which, 
in  part  at  least,  accounts  for  the  acid  reaction  to  turmeric  (Roh- 
mann).  It  is  of  great  interest  that  this  oxidative  transformation 
of  lactic  acid  only  occurs  in  muscle  whose  structure  is  so  far  pre- 
served that  its  irritability  is  not  lost.  In  minced  or  triturated 
muscle  it  does  not  take  place. 

The  relations  between  the  heat  production,  the  formation  of 
carbon  dioxide,  and  the  production  of  lactic  acid  indicate  that 
liberation  of  lactic  acid  from  some  precursor  is  an  essential  stage 
in  the  sudden,  '  explosive  '  reaction  or  series  of  reactions  which 
precedes  and  induces  the  mechanical  response  to  stimulation.  This 
stage  takes  place  whether  oxygen  be  present  or  absent,  and  it  seems 
to  be  accompanied  by  a  considerable  liberation  of  energy,  at  the 
expense  of  which  alone  the  anaerobically  contracting  muscle  works. 
It  is  most  probable  that  the  liberation  of  lactic  acid  follows  the  same 
course  in  the  muscle  abundantly  supplied  with  oxygen,  although  it 
has  not  been  shown  that  oxidative  processes,  resulting  in  the  forma- 
tion of  carbon  dioxide,  do  not  contribute  also  at  this  stage  to  the 
energy  which  is  transformed  into  the  mechanical  effect.  But  while 
in  the  absence  of  oxygen  the  reaction  stops  at  the  formation  of 
lactic  acid,  when  oxygen  is  available  the  cycle  is  completed  by 
restitution  processes  which  lead  to  the  disappearance  of  the  lactic 
acid  either  by  restoration  to  its  original  position  in  the  precursor 
from  which  it  is  derived,  or  perhaps  in  the  case  of  a  portion  of  the 
lactic  acid  to  its  combustion  to  carbon  dioxide  and  water.  For 
these  restitution  processes  oxygen  is  essential,  and  it  is  to  be 
supposed  that  the  energy  required  for  the  rebuilding  of  the  lactic 
acid  precursor,  or,  to  speak  more  generally,  for  the  restoration  of 
the  muscle  to  its  original  state  in  readiness  for  a  fresh  contraction, 
is  derived  largely  from  oxidations  in  which  carbon  dioxide  makes 
its  appearance. 

The  Precursor  of  Lactic  Acid. — What  material  is  the  lactic  acid 
formed  from  ?  There  are  reasons  for  thinking  that  lactic  acid  is  an 
intermediate  substance  which  in  metabolism  serves  as  a  link  between 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION     745 

the  products  of  protein  decomposition  and  carbo-hydrates,  and 
between  carl)o-hydrates  and  fat.  From  what  we  know  of  the 
production  of  lactic  acid  both  outside  the  bod}'  and  in  the  intestine 
from  carbo-liydrates,  it  might  seem  a  most  plausible  suggestion 
that  in  the  active  muscle  it  comes  from  glycogen. 

Glycogen  is  the  one  solid  constituent  of  muscle  which  has  been 
definitely  proved  to  diminish  during  activity.  It  accumulates  in 
a  resting  muscle,  especially  in  a  muscle  whose  motor  nerve  has  been 
cut;  but  rapidly  disappears  from  the  muscles  of  an  animal  made 
to  do  work  while  food  is  withheld;  or  from  the  muscles  of  an  animal 
poisoned  by  strychnine,which  causes  violent  muscular  contractions. 
But  the  best  evidence  points  the  other  way — e.g.,  in  rigor  mortis 
lactic  acid  is  produced  just  as  in  muscular  contraction.  Nay, 
more,  the  amount  of  lactic  acid  (as  much  as  0-5  per  cent,  expressed 
as  zinc  lactate)  produced  in  full  heat  rigor  (at  40°  to  45°  C.)  is  con- 
stant for  similar  excised  muscles.  This  '  acid-maximum  '  is  the 
same  when  fresh  muscle  is  at  once  put  into  rigor;  or  when  fatigue 
is  first  induced,  with  formation  of  lactic  acid,  before  rigor;  or, 
finally,  when  the  lactic  acid  of  the  fatigued  muscle  is  caused  to 
disappear  under  the  influence  of  oxygen,  and  heat  rigor  is  then 
brought  about  in  the  muscle  (Fletcher  and  Hopkins).  Yet  in  rigor 
mortis  the  quantity  of  glycogen  is  unaltered  (Boehm).  Further, 
under  certain  conditions  an  excised  muscle  is  capable  of  producing 
a  quantity  of  lactic  acid  much  greater  than  could  be  derived  from 
the  glycogen  contained  in  it. 

An  indirect  argument  against  the  view  that  the  lactic  acid  pre- 
cursor is  glycogen  has  been  based  by  Hill  on  the  results  of  his  studies 
on  the  heat  production  of  surviving  muscle.  From  the  amount 
of  heat  evolved,  he  calculates  that  the  precursor  of  lactic  acid 
must  have  a  heat  value  10  per  cent,  greater  than  that  of  lactic  acid. 
Now,  the  heat  of  combustion  of  dextrose  is  only  about  3  per  cent. 
more  than  that  of  lactic  acid.  He  concludes  that  the  precursor 
which  yields  lactic  acid  is  a  body  of  greater  energy  than  dextrose. 
This,  of  course,  does  not  preclude  the  possibility  that  the  complex, 
whatever  it  is,  from  which  lactic  acid  is  liberated,  contains  a  carbo- 
hydrate group.  But  it  would  not  be  profitable  to  pursue  these 
speculations  at  present.  The  facts  just  mentioned  suggest  that  it 
is  the  same  precursor  which  yields  the  lactic  acid  developed  with 
the  onset  of  rigor.  Further  evidence  of  the  close  relations  between 
the  chemical  changes  occurring  in  contraction  and  those  occurring 
in  rigor  will  be  developed  in  considering  the  latter  phenomenon. 

The  Substances  metabolized  in  Muscular  Contraction. — If  the 
liberation  of  lactic  acid  were  assumed  to  be  the  immediate  cause  of 
the  mechanical  changes  in  muscular  contraction,  if  the  nature  of 
the  body  which  yields  lactic  acid  were  known,  and  if  it  were  proved, 
which  is  far  from  being  the  case,  that  the  whole  of  the  energy  con- 


746         THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

cerned  in  initiating  and  carrying  out  the  mechanical  effect  is  derived 
from  the  decomposition  of  this  precursor,  the  question  would  still 
confront  us,  What  are  the  materials  at  the  expense  of  the  energy 
of  which  the  muscle  is  restored  to  its  original  condition  ready  for 
another  contraction  ?  If  the  lactic  acid  is  used  over  and  over 
again,  it  is  indeed  the  metabohsm  of  these  substances  which  will 
be  chiefly  represented  in  the  waste  products  given  off  by  the  muscle ; 
the  lactic  acid  complex  will  merely  represent  a  chemical  machine 
through  which  the  energy  of  these  other  substances  is  transformed 
into  mechanical  energy,  and  they  will  constitute  the  ultimate  source 
of  energy  of  the  muscular  contraction.  In  this  sense  the  muscular 
glycogen,  whether  it  yields  lactic  acid  or  not,  is  almost  certainly 
one  source  of  energy  for  the  active  muscle,  being  converted  into 
dextrose,  of  course,  before  utilization.  Dextrins  and  maltose,  the 
intermediate  products  of  this  decomposition,  have  been  detected 
in  muscle,  more  maltose,  indeed,  than  dextrose  being  present 
(Osborne),  since  the  dextrose  is  rapidly  oxidized.  Glycogen  cannot 
be  the  only  source  of  muscular  energy,  for  its  amount  is  too  small. 

For  example,  the  heart  of  an  average  man,  which  weighs  280  grammes, 
contains  about  60  grammes  of  solids,  and  among  these  certainly  not 
more  than  i  gramme  of  glycogen.  In  twenty -four  hours  it  produces 
120  calories  of  heat  (pp.  138,  663),  equivalent  to  the  complete  com- 
bustion of  a  little  less  than  30  grammes  of  glycogen.  To  supply  this 
amount,  the  whole  store  of  glycogen  in  the  heart  would  have  to  be  used 
and  replaced  every  fifty  minutes.  But  the  accumulation  of  glycogen 
is  immensely  slower  in  the  muscles  of  a  rabbit  made  glycogen-free  by 
strychnine,  and  therefore  we  have  to  look  around  for  some  other  source 
of  energy  to  supplement  the  glycogen.  We  have  already  brought 
forward  evidence  (p.  599)  that,  under  ordinary  circumstances,  not  a 
great  deal,  at  any  rate,  of  the  energy  of  muscular  contraction  comes 
from  the  proteins.  Of  carbo-hydrates,  the  only  one  except  the  glycogen 
of  the  heart  muscle  which  is  at  all  adequate  to  the  task  of  supplying  so 
much  energy  is  the  dextrose  of  the  blood.  The  quantity  of  blood 
passing  through  the  coronary  circulation  has  been  estimated  at  30  c.c. 
per  100  grammes  of  cardiac  muscle  per  minute  (Bohr  and  Henriques), 
which  would  be  equivalent  for  an  average  man  to  about  120  litres  in 
twenty-four  hours.  This  quantity  of  blood  will  contain  at  least 
120  grammes  of  dextrose,  and  about  32  grammes  will  suffice  to  supply 
all  the  heat  produced  by  the  heart.  There  is  no  reason  to  suppose  that 
this  dextrose  must  first  be  changed  into  muscular  glycogen,  which  only 
represents  a  certain  amount  of  reserve  carbo-hydrate.  Of  proteins  a 
little  less  than  30  grammes  would  be  needed,  of  fat  a  little  more  than 
12  grammes.  We  see,  therefore,  how  intense  must  be  the  metabolism 
that  goes  on  in  an  actively  contracting  muscle.  On  any  probable 
assumption  as  to  the  source  of  muscular  energy,  a  quantity  of  material 
equal  to  half  of  its  solids  must  be  used  up  by  the  heart  in  twenty-four 
hours.  Or,  to  put  it  in  another  way,  the  heart  requires  not  less  than 
two-fifths  of  its  weight  of  ordinary  solid  food  in  a  day.  The  body  as  a 
whole  requires  ^  to  ^ij  of  its  weight. 

The  general  conclusions  to  which  physiologists  have  been  led 
as  to  the  relative  importance  of  the  different  food  substances  for 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    747 

muscular  work  have  been  previously  given  (p.  601),  and  need  not 
be  repeated  here.  It  may  be  added  that  the  various  food  substances 
yield  muscular  energy  in  isodynamic  relation.  In  other  words,  a 
given  amount  of  muscular  work  requires  the  expenditure  of  approxi- 
mately the  same  quantity  of  chemical  energy,  whether  it  comes 
almost  entirely  from  protein,  or  chiefly  from  carbo-hydrates,  or 
chiefly  from  fat.  Some  observers  have  stated  that  the  taking  of 
even  a  comparatively  small  quantity  of  sugar  vastly  increases  the 
capacity  for  muscular  work  as  measured  by  the  ergograph  (p.  726). 
But  although  it  is  not  to  be  doubted  that  sugar  is  under  normal 
circumstances  one  of  the  most  important  substances  used  up  in 
muscular  contraction,  the  claim  that  sugar  is,  par  excellence,  the 
food  for  muscular  exertion  has  not  yet  been  made  out. 

Physico-Chemical  Conditions  of  Muscular  Contraction. — For  excised 
fresh  muscle  A  (p.  421)  has  been  estimated  at  o-68°  C.  But  this  is 
probably  higher  than  in  the  living  body,  for  after  excision  waste  products, 
with  their  relatively  small  and  numerous  molecules,  are  still  for  a  time 
produced,  and  are  no  longer  removed  by  the  blood.  In  salt  solutions 
isotonic  with  the  muscle  substance — e.g.,  for  the  frog's  gastrocnemius 
at  room-temperature  a  0-75  per  cent,  solution  of  sodium  chloride — the 
resting  muscle  neither  gains  nor  loses  water  for  some  hours.  The  active 
muscle  behaves  quite  differently.  When  a  muscle  immersed  in  isotonic 
salt  solution  is  tetanized,  water  enters  it,  leading  to  an  increase  in 
weight  and  a  diminution  in  specific  gravity  (Ranke,  Loeb,  Barlow). 
The  same  occurs  even  when  blood  is  circulated  through  active  muscles, 
the  blood  becoming  poorer  in  water  (Ranke).  This  may  be  explained 
by  the  increase  of  osmotic  pressure  in  the  muscle  substance  which  must 
accompany  the  decomposition  of  large  molecules  into  small.  As  fatigue 
progresses,  a  movement  of  water  in  the  reverse  direction  occurs,  and 
the  muscle  rapidly  loses  water.  Exposure  of  the  fatigued  muscle  for  a 
sufi&cient  time  to  an  atmosphere  of  oxygen  restores  the  osmotic  proper- 
ties of  the  resting  muscle.  Striking  differences  have  also  been  demon- 
strated in  the  behaviour  of  resting  and  fatigued  muscle  to  hypotonic 
solutions  or  water.  Hales  observed  long  ago  that,  on  injecting  large 
quantities  of  water  into  the  bloodvessels  of  a  dog,  so  as  to  replace  the 
blood,  marked  swelling  of  the  muscles  occurred.  This  physiological  fact 
is  well  known  to  the  pork-butchers  in  China,  who  have  given  it  a 
practical,  if  not  a  very  praiseworthy,  application  in  sophisticating  their 
product  by  increasing  its  weight  (MacGowan). 

So  long  as  the  muscular  fibres  are  uninjured  they  are  permeable  or 
impermeable  for  exactly  the  same  compounds  as  other  animal  and 
vegetable  cells.  All  substances  easily  soluble  in  media  like  ether  or 
olive  oil  readily  penetrate  them  (Overton).  To  most  salts  they  are 
relatively  impermeable,  as  is  shown  by  the  fibres  retaining  their  original 
volume  in  isotonic  solutions  of  them.  In  particular,  they  cannot  easily 
take  up  or  retain  the  salts  of  the  blood-plasma,  otherwise  the  observed 
qualitative  differences — e.g.,  the  preponderance  of  potassium  in  the 
muscle  and  sodium  in  the  plasma — could  not  be  maintained.  There  are 
facts  which  indicate  that  temporary  changes  in  the  permeability  to  ions, 
not  only  of  muscular  fibres,  but  also  of  nerve  fibres  and  other  excitable 
structures,  are  concerned  in  their  stimulation.  Potassium  salts  after  a 
time  seem  to  produce  an  effect  upon  frog's  muscle,  which  alters  its 
permeability  so  that  it  takes   up  water   from  hypertonic  solutions, 


748        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Calcium  salts  have  the  opposite  effect  (Loeb) .  Sodium  (and  in  a  minor 
degree  lithium)  salts  have  a  peculiar  relation  to  the  contraction  of 
skeletal  muscle,  for  which  they  appear  to  be  indispensable.  Yet  sodium 
chloride  produces  a  paralyzing  action  on  the  frog's  motor  nerve-endings, 
so  that  after  perfusion  with  a  solution  of  that  salt  stimulation  of  the 
motor  nerve  causes  no  contraction,  or  with  a  slighter  degree  of  paralysis 
contraction  only  after  a  long  interval.  The  eflcct  can  be  counteracted 
by  solutions  containing  calcium  salts  (Locke,  Gushing), 

Rigor  Mortis. — When  a  muscle  is  dying,  its  excitability,  after 
perhaps  a  temporary  rise  at  the  beginning,  diminishes  more  and 
more  until  it  ultimately  responds  to  no  stimulus,  however  strong. 
The  loss  of  excitability  is  not  in  itself  a  sure  mark  of  death,  for, 
as  we  have  seen,  an  inexcitable  muscle  may  be  partially  or  com- 
pletely restored;  but  it  is  followed,  or,  where  the  death  of  the  muscle 
takes  place  very  rapidly,  perhaps  accompanied,  by  a  more  decisive 
event,  the  appearance  of  rigor.  The  muscle,  which  was  before  soft 
and  at  the  same  time  elastic  to  the  touch,  becomes  firm;  but  its 
elasticity  is  gone.  The  fibres  are  no  longer  translucent,  but  opaque 
and  turbid.  If  shortening  of  the  muscle  has  not  been  opposed,  it 
may  be  somewhat  contracted,  although  the  absolute  force  of  this 
contraction  is  small  compared  with  that  of  a  living  muscle,  and  a 
slight  resistance  is  enough  to  prevent  it.  The  reaction  is  now 
distinctly  acid  to  htmus.  This  is  rigor  mortis,  the  death-stiffening 
of  muscle. 

An  insight  into  the  real  meaning  of  this  singular  and  sometimes 
sudden  change  was  first  given  by  the  experiments  of  Kiihne.  He 
took  living  frog's  muscle,  freed  from  blood,  froze  it,  and  minced  it 
in  the  frozen  slate.  The  pieces  were  then  rubbed  up  in  a  mortar 
with  snow  containing  i  per  cent,  of  common  salt,  and  a  thick  neutral 
or  alkaline  liquid,  the  '  muscle-plasma,'  was  obtained  by  filtration. 
This  clotted  into  a  jelly  when  the  temperature  was  allowed  to  rise, 
but  at  0°  C.  remained  fluid.  The  clotting  was  accompanied  by  a 
change  of  reaction,  the  liquid  becoming  acid.  An  equally  good, 
or  better,  method  is  to  use  pressure  for  the  extraction  of  the  plasma 
from  the  frozeti  fragments  of  muscle.  A  low  temperature  is  essential, 
otherwise  the  plasma  will  coagulate  rapidly  within  the  injured 
muscle.  A  similar  plasma  can  be  expressed  from  the  skeletal 
muscles  of  warm-blooded  animals  (Halliburton),  and  with  greater 
difficulty  from  the  heart. 

When  the  muscle,  after  exhaustion  with  water,  is  covered  with  a 
solution  of  a  neutral  salt,  a  5  per  cent,  solution  of  magnesium  sulphate 
or  10  per  cent,  solution  of  ammonium  chloride  being  the  best,  certain 
proteins  are  extracted  which  clot  or  are  precipitated  much  in  the  same 
way  as  the  muscle-plasma  obtained  by  cold  and  pressure;  and  the 
process  is  hastened  by  keeping  them  at  a  temperature  of  40°  C. 

In  the  extracts  of  mammalian  muscle  three  chief  proteins  are  present: 
paramyosinogen  (v.  Fiirth's  myosin),  coagulating  by  heat  at  47°  to 
50°  C. ;  myosinogen  (v.  Fiirth's  myogen),  coagulating  at  55°  to  60°  C, 
usually  about   56°) ;  and  serum-albumin,  coagulating  about  73°.     The 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    749 

serum-albumin  belongs  to  the  blood  and  lymph,  and  is  not  a  constituent 
of  the  muscle-fibre.  The  most  recent  work  on  the  subject  is  that  of 
Botazzi,  who  obtained  muscle  juice  without  the  addition  of  water  or 
salt  solutions,  by  rubbing  muscles  up  with  sand,  and  then  subjecting  the 
triturated  material  to  a  pressure  of  many  atmospheres.  He  finds  that, 
leaving  out  of  account  the  serum-albumin,  muscle  juice  contains  only 
one  protein  in  solution,  and  this  corresponds  upon  the  whole  in  its 
properties  to  myosinogen.  A  second  protein,  and  only  these  two  have 
been  proved  to  exist  in  muscle  juice,  is  not  in  solution,  but  in  the  form 
of  very  fine  granules  revealed  by  the  ultramicroscope.  This  corresponds 
in  a  general  way  to  paramyosinogen.  Botazzi  supposes  that  it  repre- 
sents the  substance  of  the  muscular  fibrils.  The  granules  show  a  ten- 
dency even  at  the  ordinary  temperature  to  agglutinate  and  to  be  pre- 
cipitated. The  process  is  hastened  by  dilution  with  water,  removal  of 
the  salts  by  dialysis,  addition  of  acids,  and  the  agglutination  and  pre- 
cipitation are  accomplished  very  rapidly  at  45''  to  55°  C,  giving  rise 
to  '  heat  coagulation.'  The  protein  in  solution  (myosinogen)  is  in- 
soluble in  distilled  water  when  thoroughly  freed  from  salts,  and  is  pre- 
cipitated by  dialysis,  but  not  so  easily  as  paramyosinogen.  The  total 
proteins  in  the  juice  obtained  by  pressure  varied  from  5*3  to  9*5  per 
cent.,  a  great  deal  of  the  muscle  protein  being,  of  course,  left  in  the 
residue.  The  granules  (paramyosinogen)  constituted  from  a  third  to 
two-thirds  of  the  protein  in  ditfcrent  experiments,  and  the  true  pro- 
portion must  have  been  considerably  higher,  since  on  account  of  their 
small  size  the  loss  in  separating  them  by  filtration  was  great.  The 
'  myosin  '  precipitate,  which  rapidly  forms  in  muscle-plasma  at  body 
temperature,  is  sometimes  called  the  muscle-clot,  and  the  liquid  which 
is  left  the  muscle-serum,  but  it  would  probably  be  better  to  avoid  these 
terms,  as  they  suggest  an  analog^'  with  the  coagulation  of  blood-plasma, 
which  is  apt  to  be  misleading.  A  similar  precipitate  or  clot  seems  to 
be  formed  in  the  interior  of  the  muscular  fibres  in  natural  rigor  and  in 
the  rapid  rigor  produced  b}^  heating  a  muscle  to  a  little  above  the  body- 
temperature.  But  in  natural  rigor  the  whole  of  the  paramyosinogen 
and  myosinogen  do  not  undergo  the  change,  since  a  certain  amount  of 
these  substances  can  as  a  rule  be  extracted  from  dead  muscle  by  saline 
solutions.  Thus,  in  rabbit's  muscles,  before  the  onset  of  rigor  mortis, 
87'3  per  cent,  of  the  total  protein  was  found  to  be  soluble  in  10  per  cent, 
ammonium  choride  solution,  and  only  12*7  per  cent,  coagulated;  while 
after  rigor  had  occurred,  7i'5  per  cent,  was  coagulated,  and  only  2S'5  per 
cent,  remained  soluble  (Saxl).  It  is  not  known  whether  in  the  living 
muscle  paramyosinogen  and  myosinogen  exist  as  such.  It  has,  indeed, 
been  stated  that,  if  a  tracing  is  taken  from  a  muscle  which  is  gradually 
heated,  it  first  shortens  at  tlie  temperature  of  coagulation  of  para- 
myosinogen, and  then  again  at  that  of  myosinogen,  and  that  in  frog's 
muscle  there  is  an  additional  shortening  at  40°,  the  temperature  at 
which  in  extracts  an  additional  heat  precipitate  occurs.  The  conclusion 
has  been  drawn  that  these  substances  must  be  present  as  such  in  the 
living  fibres,  and  that  the  successive  shortenings  are  mechanical  phe- 
nomena due  to  their  heat  coagulation.  Similar  shortenings  have  been 
described  in  nerve  and  liver  tissue  at  about  the  temperatures  at  which 
the  proteins  in  extracts  of  these  tissues  are  coagulated  by  heat.  But 
Meigs  has  shown  that  the  supposed  corretipondence  is  far  from  being 
exact,  and  tluit  muscles  whose  proteins  have  been  already  coagulated  in 
a  mixture  of  alcohol  and  salt  solution  still  show  the  typical  shortening 
on  being  heeited.  The  heat  shortening  is,  therefore,  dependent  on 
some  other  process  than  aggregation  of  the  particles  of  coagulable 
protein. 


750        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

Certain  analogies  between  rigor  and  muscular  contraction  were 
early  pointed  out.  In  both  there  is  (i)  shortening;  (2)  heat-pro- 
duction; (3)  formation  of  lactic  acid;  (4)  discharge  of  carbon 
dioxide;  (5)  electrical  changes.  As  regards  the  production  of  lactic 
acid,  there  is  reason  to  believe  that  the  process  is  fundamentally 
the  same  as  in  contraction,  and  the  study  of  rigor,  especially  of 
certain  of  the  artificially  induced  forms — e.g.,  heat  rigor — ^in  relation 
to  the  liberation  of  lactic  acid,  carbon  dioxide,  and  heat,  has  thrown 
light  upon  the  changes  normally  occurring  in  muscle.  Another 
analogy  might  be  forced  into  the  list  by  anyone  who  was  deter- 
mined to  see  only  rigor  in  contraction:  the  rigor  passes  off  as  the 
contraction  passes  off,  although  the  '  resolution  '  of  a  rigid  muscle 
takes  days,  the  relaxation  of  an  active  muscle  a  fraction  of  a  second. 
The  disappearance  of  rigor  is  not  dependent  on  putrefaction;  it 
takes  place  when  growth  of  bacteria  is  prevented  (Hermann), 
Possibly  it  is  connected  with  autolytic  processes  due  to  intracellular 
ferments  (p.  588). 

Why  does  coagulation  of  myosin  occur  at  the  death  of  the  muscle  ? 
To  this  question  no  clear  answer  can  be  given.  Some  have  looked 
on  the  process  as  analogous  to  the  clotting  of  blood  when  it  is  shed, 
and  it  has  even  been  suggested  that  just  as  a  fibrin  ferment  is 
developed  when  the  leucocytes  and  blood-plates  begin  to  die,  a 
myosin  ferment,  which  aids  coagulation,  is  developed  in  dead  or 
dying  muscle.  But  no  proof  has  been  given  of  the  existence  of  such 
a  ferment.  And  it  is  easy  to  make  too  much  of  the  apparent 
analogy  between  the  clotting  of  muscle  and  the  clotting  of  blood, 
for  there  are  differences  as  well  as  resemblances.  For  instance,  the 
addition  of  potassium  oxalate  does  not  prevent  coagulation  of 
muscle  extracts,  as  it  does  of  blood  and  blood-plasma.  If  the 
development  of  lactic  acid  in  the  muscle  is  not  the  primary  cause 
of  the  coagulation  which  constitutes  the  essential  feature  of  rigor 
mortis,  it  seems  to  be  closely  related  to  it.  For  when  excised 
muscles  are  abundantly  supplied  with  oxygen,  no  lactic  acid 
accumulates  in  them,  and  the  final  loss  of  excitability  of  the  muscle 
is  not  followed  by  rigor.  In  any  case,  direct  precipitation  of 
hitherto  unclotted  muscle  proteins  may  be  induced  by  the  acid,  or 
the  acid  salts  formed  in  its  presence.  Deficiency  of  oxygen  is 
associated  with  the  occurrence  of  rigor  mortis,  as  it  is  with  the 
accumulation  of  lactic  acid,  and  a  developing  rigor  can  be  abolished 
by  oxygen,  and  its  onset  long  or  indefinitely  delayed.  When  strict 
aseptic  technique  is  observed  an  excised  sartorius  muscle  of  the 
frog  may  remain  irritable  in  sterile  Ringer's  solution,  even  without 
oxygenation,  for  as  long  as  three  weeks  (Mines). 

Various  influences  affect  the  onset  of  rigor.  Fatigue  hastens 
it;  heat  has  a  similar  effect;  the  contact  of  caffeine,  chloroform, 
and  other  drugs  causes  most  pronounced  and  immediate  rigor 


CHEMICAL  PHENOMENA  OF  MUSCULAR  CONTRACTION    751 

Blood  applied  to  the  cross-section  of  a  muscle  first  stimulates  the 
fibres  with  which  it  is  in  contact,  and  then  renders  them  rigid. 
But  it  is  to  be  remembered  that  normally  the  blood  does  not  come 
into  direct  contact  even  with  the  sarcolemma,  much  less  with  its 
contents. 

The  effect  of  heat  is  of  special  interest.  A  skeletal  muscle  of 
a  frog,  like  the  gastrocnemius,  if  dipped  into  physiological  saline 
solution  at  40°  or  41°  C.  goes  into  rigor  at  once;  the  frog's  heart 
requires  a  temperature  3°  or  4°  higher;  the  distended  bulbus  aortse 
can  withstand  even  a  temperature  of  48°  for  a  short  time.  An 
excised  mammalian  muscle  passes  into  immediate  rigor  at  45°  to 
50°.  In  heat  rigor  the  reaction  of  the  muscle  becomes  strongly 
acid  owing  to  the  formation  of  lactic  acid,  and  the  evolution  of 
carbon  dioxide  is  also  increased. 

The  total  discharge  of  carbon  dioxide  in  heat  rigor  induced  at  40° 
amounts  to  35  to  40  c.c.  per  100  grammes  of  muscle.  An  additional 
15  to  20  per  cent,  is  obtained  on  heating  to  75°  C.  to  completely  coagu- 
late the  proteins,  and  a  further  15  to  20  per  cent,  on  heating  to  about 
100°  C.  When  a  muscle  is  scalded  by  being  suddenly  immersed  in 
boiling  salt  solution,  lactic  acid  is  not  formed,  but  carbon  dioxide  to  the 
amount  of  60  to  70  per  cent,  is  discharged.  An  excised  muscle  kept  in 
oxygen  for  many  hours,  during  which  it  has  discharged  several  times 
as  much  caibon  dioxide  as  is  ever  liberated  by  heating,  still  yields  the 
normal  discharge  on  heating  whether  to  40°  C.  or  to  100°  C.  On  the 
other  hand,  previous  survival  in  an  anaerobic  atmosphere  (of  nitrogen) 
reduces  greatly  or  abolishes  the  yield  of  carbon  dioxide  at  40°  C, 
although  not  that  at  100°  C,  the  sum  of  the  carbon  dioxide  given  off  to 
the  atmosphere  of  nitrogen  and  that  given  off  on  heating  to  100°  C. 
being  about  equal  to  the  total  amount  which  would  have  been  dis- 
charged by  a  freshly-excised  muscle  on  heating  first  to  40°  C.  and  then 
to  100°  C.  If  acid  is  added  to  a  fresh  muscle  at  about  0°  C.  even  more 
carbon  dioxide  is  liberated  than  in  heat  rigor,  while  the  yield  of  lactic 
acid  is,  even  after  many  hours,  very  little  increased  above  the  normal 
amount  for  fresh  resting  muscle.  When  the  acidified  muscle  after  the 
discharge  of  the  carbon  dioxide  is  now  heated  to  40°  C,  the  yield  of 
lactic  acid  is  increased,  but  only  traces  of  carbon  dioxide  are  given  ofi. 

From  these  and  similar  observations,  Fletcher  concludes  that  the 
carbon  dioxide  discharged  during  heat  rigor  at  40°  C.  is  pre-existent 
carbon  dioxide  set  free  from  carbonates  or  other  compounds  by 
the  lactic  acid  known  to  be  produced  in  heat  rigor.  The  carbon 
doxide  discharged  at  75°  and  100°  C.  he  regards  as  held  by 
muscle  colloids  or  in  combination  with  amino-acid  groups.  These 
results  render  untenable  the  '  inogen  '  theory  (p.  266),  with  its 
assumption  that  '  intramolecular  oxygen  '  is  stored  away  in  the 
muscle,  which  was  largely  based  upon  erroneous  observations  on 
the  discharge  of  carbon  dioxide  from  heated  muscles.  According 
to  this  theory,  carbon  dioxide  and  lactic  acid  were  supposed  to  arise 
from  a  common  precursor  into  which  oxygen  had  been  previously 
introduced. 


752        THE  PHYSIOLOGY  OF  THE  CONTRACTILE  TISSUES 

The  production  of  heat  in  heat  rigor  is  also  of  great  interest. 
Hill  has  shown  that  it  amounts  to  from  o-6  to  i-o  gramme  calorie 
per  gramme  of  muscle.  Of  this  no  more  than  005  calorie  can  be 
due  to  the  heat  of  neutralization  of  lactic  acid  by  the  sodium 
bicarbonate  in  the  muscle,  with  which  it  reacts  as  soon  as  it  is 
liberated.  The  rest  of  the  heat  is  associated  with  the  chemical 
reaction  by  which  lactic  acid  is  formed  from  its  precursor,  a  reaction 
which,  there  is  every  reason  to  believe,  is  the  same  as  that  which 
occurs  in  muscular  contraction.  The  heat  production  can  only 
be  due  in  very  shght  degree  to  the  physical  alteration  (clotting  or 
precipitation)  of  the  muscle  proteins. 

The  so-called  rigor  caused  by  water,  which  is  not  a  true  rigor, 
causes  no  increase  in  the  carbon  dioxide  given  off.  Chloroform, 
on  the  other  hand,  produces  a  marked  increase  in  the  carbon 
dioxide  production,  and  this  is  evidently  related  to  its  action  in 
hastening  the  onset  of  rigor.  Rigor  mortis  is  to  some  extent  in- 
fluenced by  the  nervous  system,  for  section  of  its  nerves  retards 
the  onset  of  rigor  in  the  muscles  of  a  hmb.  Ante-mortem  stimula- 
tion of  the  peripheral  ends  of  the  vagi,  even  with  currents  too  weak 
to  cause  a  perceptible  effect  upon  the  heart-beats,  prolongs  the 
period  of  spontaneous  contraction  and  the  irritability  of  the  ven- 
tricles after  death,  and  retards  the  onset  of  rigor  (Joseph  and 
Meltzer).  Cold  rigor  is  obtained  when  frog's  muscles  are  cooled 
to  —15°  C.  The  muscles  remain  perfectly  translucent.  They 
do  not  recover  their  irritability  on  thawing,  but  if  cooled  only  to 
—  7°  C.  they  recover  (Folin). 

In  a  human  body  rigor  generally  appears  not  earlier  than  an 
hour,  and  not  later  than  four  or  five  hours,  after  death.  In  ex- 
ceptional cases,  however,  it  may  come  on  at  once,  and  the  annals 
of  war  and  crime  contain  instances  where  a  man  has  been  found 
after  death  still  holding  wjth  a  firm  grip  the  weapon  with  which 
he  had  fought,  or  which  had  been  thi'ust  into  his  hand  by  his 
murderer  (so-called  cataleptic  rigor).  It  is  related  that  after 
one  of  the  battles  of  the  American  Revolutionary  War  some  of  the 
dead  were  found  with  one  eye  open  and  the  other  closed  as  in  the 
act  of  taking  aim.  A  high  temperature  favours  a  rapid  onset;  a 
body  wrapped  up  in  bed  will,  other  things  being  equal,  become  rigid 
sooner  than  a  body  lying  stripped  in  a  field.  Muscular  exhaustion, 
as  we  have  said,  is  another  favouring  condition:  hunted  animals 
and  the  victims  of  wasting  diseases  go  quicldy  into  rigor.  It  is 
a  rule,  but  not  an  invariable  one,  that  rigor,  when  it  comes  on 
quickly,  is  short,  and  lasts  longer  when  it  comes  on  late.  All  the 
muscles  of  the  body  do  not  stiffen  at  the  same  time;  the  order 
is  usually  from  above  downwards,  beginning  at  the  jaws  and  neck, 
then  reaching  the  arms,  and  finally  the  legs.  After  two  or  three 
days  the  rigor  disappears  in  the  same  order.     The  position  of  the 


CHEMICAL  PHENOMENA   OF  MUSCULAR  CONTRACTION    753 

limbs  in  rigor  is  the  same  as  at  death;  the  m.usclcs  stiffen  without 
any  marked  contraction.  This  can  be  strikingly  shown  on  a  newly- 
killed  animal  by  cutting  the  tendons  of  the  extensors  of  one  foot 
and  the  flexors  of  the  other;  when  natural  rigor  comes  on,  the  feet 
remain  just  as  they  were.  If  heat  rigor,  however,  is  caused,  the 
one  foot  becomes  rigid  in  flexion  and  the  other  in  extension;  and 
the  contraction-force  is  considerable,  although  not  so  great  as  that 
of  an  electrical  tetanus  in  a  living  muscle. 

The  Possibility  of  Recovery  of  Muscles  after  Rigor. — When  the  circu- 
lation in  the  hind  legs  of  rabbits  is  interrupted  by  compression  or 
ligation  of  the  abdominal  aorta  (Stenson's  experiment),  the  muscles  lose 
tlieir  excitability,  but  speedily  recover,  if  they  have  not  been  deprived 
of  arterial  blood  for  too  long  a  time,  when  the  blood  is  again  allowed  to 
reach  them.  A  longer  interruption  of  the  circulation  leads  not  only 
to  total  inability  to  respond  to  stimulation,  but  also  to  rigor,  and  most 
observers  are  agreed  that,  as  regards  the  skeletal  muscles  at  least,  this 
is  the  irrevocable  end  of  excitability.  Brown-Sequard,  indeed,  stated 
that  after  the  full  development  of  rigor  in  the  rabbit's  muscles  (Stenson's 
experiment),  and  also  in  the  hand  of  an  executed  criminal  through 
which  an  artificial  circulation  was  established,  recovery  ensued.     But 

Erobably  the  rigor  was  incomplete  or  did  not  involve  all  the  fibres.  In 
eart  muscle  the  conditions  appear  to  be  somewhat  different,  and  Heubel 
has  alleged  that  rhythmical  contractions  of  the  frog's  heart  can  be 
restored  by  filling  its  cavity  with  blood,  after  rigor  has  been  caused  by 
heat  and  in  other  ways,  and  we  have  already  seen  that  the  same  is  true 
of  the  mammalian  heart  after  the  onset  of  rigor.  Excised  frog's 
muscles  which  have  undergone  rigor  mortis  become  less  stiff  when 
exposed  to  an  atmosphere  of  oxygen. 


ab 


CHAPTER  XIV 

NERVE 

The  voluntary  movements  are  originated  by  efferent  or  outgoing 
impulses  from  the  brain,  which  reach  the  muscles  along  their 
motor  nerves.  The  involuntary  movements  and  the  secretions 
are  in  many  cases  able  to  go  on  in  the  absence  of  central  connec- 
tions, but  are  normally  under  central  control.  Afferent  impulses 
are  continually  ascending  to  the  cord  and  brain  from  the  skin, 
joints,  bones,  muscles,  and  organs  of  special  sense  like  the  eye  and 
the  ear.  Everywhere  the  connection  between  the  nervous  centres 
and  the  peripheral  organs,  and  between  different  parts  of  the 
central  nervous  system,  is  made  by  nerve-fibres.  Those  which 
run  outside  the  brain  and  cord  are  called  peripheral  nerve-fibres 
to  distinguish  them  from  the  intracentral  fibres  of  the  central 
nervous  system  itself. 

In  this  chapter  we  propose  to  consider  certain  of  the  general 
properties  of  nerve-fibres.  Most  of  our  knowledge  of  these  proper- . 
ties  has  been  derived  from  experiments  on  the  peripheral,  and 
particularly  the  peripheral  motor  nerves;  but  there  is  every  reason 
to  believe  that  the  main  results  are  true  of  all  nerve-fibres,  afferent 
and  efferent,  peripheral  and  central. 

What  we  call  nerve-fibres  were  known  and  named,  and  many  im- 
portant facts  in  their  physiology  discovered,  long  before  their  true 
morphological  significance  was  recognized.  The  researches  of  recent 
years  have  shown  that  every  nerve-fibre  is,  as  regards  its  essential  con- 
stituent the  axis-cylinder,  a  process  of  a  nerve-cell.  The  nerve-cells, 
each  of  which,  including  all  its  processes,  may  be  conveniently  termed 
a  neuron,  are  the  essential  elements  of  the  nervous  system.  The  cell- 
bodies  of  most  of  the  neurons  are  situated  in,  or  in  close  relation  to,  the 
spinal  cord  and  the  brain,  and  therefore  the  detailed  description  of 
them  will  be  reserved  till  we  come  to  treat  ol  the  central  nervous  system 
(see  p.  822  and  Figs.  318  to  330).  It  is  enough  to  say  here  that  in 
general  a  nerve-cell  gives  off  two  kinds  of  piocesscs:  (i)  one  br  more 
dendrites  or  protoplasmic  processes,  which  repeatedly  bifurcate  like  the 
branches  of  a  tree  into  thinner  and  thinner  twigs,  and  extend  only  for 
a  relatively  short  distance  from  the  cell-body;  (2)  an  axis-cylinder 
process  or  axon,  which  as  a  rule  runs  for  a  considerable  distance  without 
altering  its  calibre,  and  either  gives  off  no  branches  (as  in  the  peripheral 
nerves)  or  only  a  comparatively  small  number  of  lateral  twigs  (col- 

754 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE       755 

laterals).  Ultimately  the  axis-cylinder  process  and  its  collaterals,  if  it 
has  any,  end  by  breaking  up  into  a  brush,  a  plexus  or  a  feltwork  or 
basketwork  of  fibrils.  The  ax^ns  of  dillerent  nerve-cells  vary  greatly 
in  length.  Some  terminate  within  the  grey  matter  of  the  brain  or  spinal 
cord  not  far  from  their  origin;  others  run  in  the  white  tracts  of  the 
central  nervous  system  or  in  the  peripheral  nerves  for  half  the  height 
of  a  man.  All  except  the  shortest  axis-cylinder  processes  become 
clothed  at  a  little  distance  from  the  cell-body  with  a  protective  covering, 
which  continues  to  invest  them  (and  their  collaterals)  througliout  the 
rest  of  their  course,  disappearing  only  when  they  begin  to  break  up  at 
their  terminations.  An  axis-cylinder  process  (spoken  of  simply  as  the 
axis-cylinder,  when  considered  apart  from  the  nerve-cell)  constitutes, 
with  its  covering,  a  nerve-fibre. 

The  axis-cylinder  is  the  essential  conducting  part  of  the  fibre,  for  it  is 
present  in  every  nerve-fibre,  running  from  end  to  end  of  it  without  break, 
and  towards  the  periphery  it  is  alone  present.  It  is  made  up  of  fine 
longitudinal  fibrils  embedded  in  interstitial  substance  (Fig.  319,  p.  823). 
Such  a  fibrillar  structure  is  best  shown  after  treatment  of  the  nerve - 
fibres  with  certain  reagents,  although  it  is  certain  that  it  exists  pre- 
formed in  the  living  fibres. 

Section  I. — The  Nerve- Impulse  or  Propagated  Disturbance: 
ITS  Initiation  and  Conduction. 

So  far  as  we  know,  the  only  function  of  nerve-fibres  is  to  conduct 
impulses  from  nerve-centres  to  peripheral  organs,  or  from  peripheral 
organs  to  nerve-centres,  or  from  one  nerve-centre  to  another. 
In  the  normal  body  these  impulses  never,  or  only  very  rarely, 
originate  in  the  course  of  the  nerve-fibres;  they  are  set  up  either 
at  their  peripheral  or  at  their  central  endings.  By  artificial  stimu- 
lation, however,  a  nerve-impulse  may  be  started  at  any  part  of  a 
fibre,  just  as  a  telegram  may  be  dispatched  by  tapping  any  part  of 
a  telegraph  wire,  although  it  is  usually  sent  from  one  fixed  station 
to  another. 

Nature  of  the  Nerve- Impulse.— What  the  nerve-impulse  actually 
consists  in  we  do  not  know.  All  we  know  is  that  a  change  or  dis 
turbance  of  some  kind,  of  which  the  most  evident  token  is  an 
electrical  change,  passes  over  the  nerve  \\ath  a  measurable  velocity, 
and  gives  tidings  of  itself,  if  it  is  travelling  along  efferent  fibres — 
that  is,  out  from  the  central  nervous  system — by  the  contraction 
or  inhibition  of  muscle  or  by  secretion;  if  it  is  travelling  along 
afferent  fibres — that  is,  up  to  the  central  nervous  system — by  sensa- 
tion, or  by  reflex  muscular  or  glandular  effects. 

Whether  the  wave  which  passes  along  the  nerve  is  a  wave  of 
chemical  change  (such,  to  take  a  very  crude  example,  as  runs 
along  a  train  of  gunpowder  when  it  is  fired  at  one  end),  or  a  wave 
of  mechanical  change,  a  peculiar  and  most  deUcate  molecular 
shiver,  if  we  may  so  phrase  it,  or  a  shear  in  a  definite  direction  along 
the  colloidal  substance  of  the  axis-cylinder  (Sutherland),  there  is 
no    absolutely    definite    experimental    evidence    to    decide.     An 


756  NERVE 

electrical  change  accompanies  the  nerve-impulse  travelling  at  the 
same  rate,  and  although  this  is  to  be  distinguished  from  the  impulse 
itself,  there  is  little  doubt  that  the  latter  is  essentially  connected 
with  a  disturbance  of  the  electrical  equilibrium  of  the  nerve- 
substance. 

An  attempt  has  been  made  to  settle  the  question  by  determining  the 
temperature  coefficient  of  the  velocity  of  conduction  of  the  impulse  — 
i.e.,  the  quantity  which  measures  the  change  of  velocity  for  a  given 
change  of   temperature.      For  most  physical  processes  the   quotient 

ve  oci  y  a — «+£o   where  T«  is  any  given  temperature,  is  not  greater 

velocity  aXTn  ■'  ° 

than  I '2,  while  for  frog's  sciatic  nerve  the  temperature  coefficient  for 
the  most  part  lies  between  2  and  3  (Snyder).  The  mean  value  of  a 
large  number  of  observations  is  1-79,  with  Tn^  8°  to  9°  C.  (Lucas).  For 
the  pedal  nerve  of  the  giant  slug  the  mean  value  of  the  temperature 
coefficient  is  1-78  (Maxwell).  In  other  words,  while  for  the  majority  of 
physical  processes  an  increase  oi  10°  C.  increases  the  velocity  of  the 
process  by  at  most  one-fifth,  the  same  increase  of  temperature  increases 
the  velocity  of  conduction  of  the  nerve-impulse  by  four-fifths,  or  even 
more.  While  it  is  true  that  it  may  not  be  entirely  safe  to  apply  such  a 
criterion  to  a  biological  process  which  need  not  be  either  entirely  chemical 
or  entirely  physical,  and  very  likely  is  a  complex  one,  the  suggestion, 
so  far  as  it  goes,  is  undoubtedly  in  favour  of  the  chemical  hypothesis. 
That  chemical  changes  go  on  in  living  nerve  we  need  not  hesitate  to 
assume;  and,  indeed,  if  the  circulation  through  a  limb  of  a  warm- 
blooded animal  be  stopped  for  a  short  time,  the  nerves  lose  their 
excitability.  Even  the  nerves  of  cold-blooded  animals  gradually 
become  inexcitable  and  incapable  of  conduction  when  placed  in  an 
oxygen-free  medium,  as  the  oxygen  already  contained  in  the  tissue  is 
exhausted.  The  excitability  and  conductivity  of  the  nerve  are  restored 
by  oxygen.  It  is  clear,  then,  that  even  a  resting  nerve  requires  oxygen, 
and  it  can  be  shown  that  the  loss  of  function  is  acceleiated  by  stimulation 
in  the  absence  of  oxygen.  But  the  metabolism  is  very  slight  compared 
with  that  in  muscle  or  gland.  Until  recently  even  in  active  nerve  no 
measurable  production  of  carbon  dioxide  had  ever  been  observed,  nor, 
in  fact,  had  any  chemical  difference  between  the  excited  and  the  resting 
state  ever  been  unequivocally  made  out.  However,  it  has  been 
announced  that  by  the  aid  of  an  extremely  delicate  method  of  estimating 
small  quantities  of  carbon  dioxide,  a  measurable  production  of  carbon 
dioxide  can  be  detected  even  in  resting  frogs'  nerves,  and  that  this  pro- 
!  duction  is  increased  two  to  three  times  on  stimulation  (Tashiro).  This 
result  is  somewhat  puzzling  in  view  of  the  fact  that  neither  in  cold- 
blooded nor  in  mammalian  nerves  is  there  any  sensible  rise  of  temper- 
ture  during  stimulation.  With  the  apparatus  shown  in  Fig.  265  (an 
electrical  resistance  thermometer  or  bolometer  whose  use  depends  upon 
the  fact  that  the  electrical  resistance  of  a  metallic  conductor  varies 
with  its  temperature)  an  increase  even  of  0-0003°  C.  in  the  temperature 
of  the  sciatic  nerves  of  dogs  could  not  be  detected  during  tetanization. 
RoUeston  failed  to  find  evidence  of  a  rise  of  even  0*0002°  C.  in  frog's 
nerves  during  stimulation.  And  according  to  the  latest  investigation 
with  a  more  suitable  and  much  more  sensitive  thermo-electric  arrange- 
ment, the  passage  of  a  single  nerve  impulse  along  a  frog's  nerve  cannot 
be  associated  with  an  increase  of  temperature  in  the  nerve  of  even  the 
hundredth  million  of  a  degree  (A.  V.  Hill).  The  difficulty  of  inducing 
fatigue  iB  nerves  under  ordinary  conditions  has  been  considered  a  strong 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     757 


support  of  the  physical  nature  of  the  conduction  process.  Neverthe- 
less, it  is  possible  to  show  by  special  methods  that  nerve  can  be  tempor- 
arily fatigued,  although  it  recovers  very  rapidly.  When  a  mcdullated 
nerve  is  stimulated,  a  brief  period  ensues  during  which  it  refuses  to 
respond  to  a  second  stimulus.  This  refractory  period  is  normally  very 
short — not  more  than  0-002  second  for  the  frog's  sciatic.  But  it  can 
be  greatly  prolonged  by  cold,  asphyxia,  or  anaesthesia,  especially  by 
the  alkaloid  yohimbine  (Tait  and  Gunn),  and  when  the  refractory  period 
is  thus  prolonged,  fatigue  phenomena  are  readily  induced  bystimulation. 
And  while  the  nerves  of  warm-blooded  animals  at  body  temperature 
and  those  of  cold-blooded  animals  at  about  32''  C.  can  hardly  be  shown 
to  undergo  fatigue  when  tetanized  in  atmospheric  air,  fatigue  phe- 
nomena are  easily  elicited  when  the  temperature  is  lowered  even 
although  air  is  supplied  (Thorner). 

Stimulation  of  Nerve. — With  some  differences,  the  same  stimuli 
are  effective  for  nerve  as  for  muscle  (p.  711) ;  but  chemical  stimula- 
tion is  not  in  general  so  easily  obtained.     The   so-called  thermal 


Fig.  265. —  Electrical  -  Resistance 
Thermometer  (Natural  Size)  as 
used  for  investigating  heat -pro- 
duction in  mammalian  nerves  in 
situ.  A,  a  piece  of  hard  rubber  in 
the  hook-shaped  part  of  which  the 
fine  platinum  wire  P  is  fixed,  and 
covered  with  insulating  varnish; 
c,  c,  thick  copper  wires  connected 
with  P,  fastened  in  grooves,  and 
covered  with  paraffin.  Above  they 
end  in  contact  with  the  small 
binding  posts,  Bj,  Bg.  B  is  a  hard 
rubber  sliding  piece,  with  a  slot  *. 
When  B  is  in  position  the  screw,  a, 
projects  through  the  slot.  By  a  nut 
on  this  screw  B  is  fixed  on  A  when 
the  nerve  has  been  arranged  in  the 
groove. 


B  B 


A 


((fez^f 


stimulation  is  not  a  real  stimulation  due  to  the  sudden  change  of 
temperature.  The  irregular  contractions  of  the  muscle  caused  by 
the  local  application  of  heat  to  the  nerve  are  dependent  on  desicca- 
tion of  the  nerve. 

Chemical  Stimulation. — When  hyper-  or  hypotonic  solutions  are  em- 
ployed, the  withdrawal  or  entrance  of  water  may  be  an  important  factor. 

For  salts  which  penetrate  the  fibres  with  cfjual  difficulty  this  factor 
can  be  eliminated  by  applying  them  as  isotonic  solutions.  There  is 
evidence  that  chemical  stimulation  proper,  as  distinguished  from  the 
stimulation  produced  by  changes  in  the  water  content  of  the  fibres  by 
osmosis,  is  connected  with  the  electrical  charges  on  the  dissociated  ions 
of  the  salts  (p.  422).  Electrical  stimulation,  indeed,  may  only  be  a 
variety  of  chemical  stimulation  (Loeb,  Mathews,  etc.). 

Mechanical  Stimulation  may  be  applied  to  a  nerve  by  allowing  a  small 
weight  to  fall  on  it  from  a  definite  height  or  by  permitting  mercury  to  drop 
upon  it  from  a  vessel  with  a  fine  outflow  tube.  A  regular  tetanus  may 
thus  be  obtained.  Tigcrstcdt  foimd  that  the  smallest  amount  of  .vork 
spent  on  a  frog's  nerve  which  would  suffice  to  excite  it  was  a  little  less 


758  NERVE 

than  a  gramme-millimetre — ^that  is,  the  work  done  by  a  gramme  falling 
through  a  distance  of  a  millimetre,  or  (taking  an  erg  as  equivalent  to 
loVo  gramme-centimetre)  about  loo  ergs.  No  doubt  a  great  part  of 
this  is  wasted,  as  a  much  smaller  quantity  of  work  done  by  a  beam  of 
light  on  the  retina  or  by  an  electrical  current  on  an  isolated  nerve,  both 
of  which  may  be  supposed  to  act  more  directly  on  the  excitable  con- 
stituents, suffices  to  cause  stimulation.  Thus,  the  work  done  by  the 
minimal,  natural  or  specific,  stimulus  for  the  retina  in  the  form  of  green 

hght  may  be  as  little  as  — -g  erg  (S.  P.  Langley),  or  only  one-ten-thousand- 

millioneth  part  of  the  minimum  work  necessary  for  mechanical  stimula- 
tion. Again,  with  electrical  stimulation  (closure  of  a  voltaic  cm  rent, 
or  condenser  discharges)  it  has  been  shown  that  an  amount  of  work 

equal  to  — ^  erg  may  be  enough  to  cause  excitation  of  a  frog's  nerve. 

This  is  ten  thousand  times  as  great  as  the  minimal  luminous  stimulus, 
but  a  million  times  less  than  the  minimal  mechanical  stimulus. 

The  laws  of  electrical  stimulation  for  nerve  are  essentially  the  same 
as  those  we  have  already  discussed  for  muscle  (p.  715).  The  voltaic 
current  stimulates  a  nerve,  as  it  does  a  muscle,  at  closure  and  opening. 
During  the  flow  of  the  current,  so  long  as  its  intensity  remains  constant, 
there  is  as  a  rule  no  excitation,  or  at  least  none  which  is  propagated 
along  the  nerve,  so  that  the  muscles  supplied  by  it  remain  uncontracted. 
But  under  certain  conditions — for  example,  when  the  nerve  is  more 
excitable  than  usual  (as  is  the  case  with  nerves  taken  from  frogs  which 
have  been  long  kept  in  the  cold) — a  closing  tetanus  may  be  seen  while 
the  current  continues  to  pass  through  the  nerve,  and  an  opening  tetanus 
after  it  has  ceased  to  flow,  just  as  when  the  current  is  led  directly 
through  the  muscle.  Sensory  nerve-fibres,  too,  are  stimulated  by  a 
voltaic  current  during  the  whole  time  of  flow.  Induction  shocks  are 
relatively  more  powerful  stimuli  for  nerve  than  the  make  or  break  of  a 
voltaic  current.  The  opposite,  as  we  have  seen,  is  true  of  muscle;  and, 
upon  the  whole,  we  may  say  that  muscle  is  more  sluggish  in  its  response 
to  stimuli,  and  is  excited  less  easily  by  very  brief  currents,  than  nerve 
is.  An  apparent  illustration  of  this  difference  is  the  fact  that  the 
nervous  excitation  has  no  measurable  latent  period,  while  muscular 
excitation  has.  But  it  is  quite  possible  that,  if  the  conditions  of  experi- 
ment were  as  favourable  in  nerve  as  in  muscle,  a  sensible  latent  period 
might  be  found  here  too. 

In  nerve  as  in  muscle,  strength  of  stimulus  and  intensity  of  response 
correspond  within  a  fairly  wide  range,  when  we  take  the  height  of  the 
muscular  contraction  or  the  amount  of  the  negative  variation  (p.  797) 
as  the  measure  of  the  nervous  excitation.  Summation  of  stimuli,  super- 
position of  contractions,  and  complete  tetanus,  are  caused  by  stimulating 
the  muscle  through  its  nerve,  just  as  by  stimulating  the  muscle  itself 
(P-  730)- 

Excitability  of  Nerve. — It  has  usually  been  stated  that  the  ex- 
citability of  frog's  nerve,  as  measured  by  the  muscular  response  to 
i stimulation,  is  increased  by  rise  of  temperature,  and  diminished  by 
fall  of  temperature.  It  has,  however,  been  shown  that  this  increase 
of  excitability  is  only  apparent,  and  due  to  the  strengthening  of 
the  current  by  diminution  of  the  resistance,  since  the  resistance 
of  all  animal  tissues,  like  that  of  electrolytic  conductors  in  general, 
diminishes  as  the  temperature  rises  (Gotch).     When  precautions 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE      759 

are  taken  to  keep  the  current  intensity  the  same  at  the  various 
temperatures  compared,  it  is  found  that  coohng  of  a  (frog's)  nerve, 
even  to  5°  C,  increases  the  excitabihty  for  currents  of  long  duration 
(several  hundredths  of  a  second).  It  has,  indeed,  been  shown  both 
for  muscle  and  for  nerve  that  the  cooler  tissue  requires  a  smaller 
current  strength  for  its  excitation  when  the  current  is  of  long  dura- 
tion. With  brief  currents  this  effect  is  masked,  either  partially  or 
completely,  by  the  greater  increase  of  current  strength  needed  in  the 
case  of  the  cooler  tissue  to  compensate  fora  given  decrease  in  duration 
(p.  763)  (Lucas  and  Mines).  This  is  the  reason  that  for  induction 
shocks  or  voltaic  currents  of  short  duration,  the  excitability  of  the 
nerve  seems  to  be  increased  by  a  rise  of  temperature  (up  to  about 
30°  C.  in  the  case  of  frog's  nerve),  and  diminished  by  cooling. 

Drying  of  a  nerve  at  first  increases  its  excitability;  and  the  same  1 
is  true  of  separation  of  a  nerve  from  its  centre.     In  the  latter  case 
the  increase  of  irritability  begins  at  the  proximal  end  of  the  nerve, 
and  travels  towards  the  periphery.     As  time  goes  on,  the  excita- 
bility diminishes,  and  ultimately  disappears  in  the  same  order 
(Ritter-Valli  Law).     At  a  certain  stage  it  may  be  found  that  a 
given  stimulus  causes  a  smaller  and  smaller  contraction  the  farther 
down  the  nerve — that  is,  the  nearer  to  the  muscle — it  is  applied. 
On  this  was  based  the  now  abandoned  '  avalanche  theory,'  according 
to  which  the  impulse  continually  unlocked  new  energy  as  it  passed 
along  the  nerve,  and  so  gathered  strength  in  its  course  like  an 
avalanche.     It  is  now  known  that  no  material  change  takes  place 
in  the  intensity  of  the  excitation  while  it  is  being  propagated  along 
a   normal    uninjured   nerve.     For   instance,    experiments    on    the 
phrenic  nerve,  in  its  natural  position,  and  with  all  its  connections 
intact,  have  shown  that  with  a  given  strength  of    stimulus  the 
amount  of  contraction  of  the  diaphragm  is  the  same  whether  the 
nerve  be  excited  in  the  upper,  middle,  or  lower  portion  of  its  course. 
In  the  above  experiment  on  the  isolated,  and  therefore  injured,  ; 
nerve,  the  contraction  varies  in  height  with  the  distance  of  the  I 
point  of  stimulation  from  the  muscle,  not  because  the  excitation 
grows  as  it  travels,  but  because  it  is  already  greater  at  the  moment  | 
when  it  sets  out  from  a  point  near  the  central  end  of  the  nerve  ' 
than  at  the  moment  when  it  sets  out  from  a  point  near  the  muscle. 

Electrotonus. — Although  the  constant  current  does  not,  unless 
it  is  very  strong  or  the  nerve  very  irritable,  cause  stimulation  during 
its  passage,  it  modifies  profoundly  the  excitability  and  conductivit}' 
of  the  nerve.  In  the  neighbourhood  of  the  kathode  the  excitabihty 
is  increased  (condition  of  katelectrotonus),  while  around  the  anode 
it  is  diminished  (anelectrotonus).  Immediately  after  the  opening 
of  the  current  these  relations  are  for  a  brief  time  reversed,  the 
excitability  of  the  post-kathodic  area  (area  which  was  at  the  kathode 
during  the  flow)  being  diminished,  and  that  of  the  post-anodic 


700 


NERVE 


increased.  In  the  intrapolar  area  there  is  one  point  the  excita- 
bihty  of  which  is  not  altered.  This  indifferent  point,  as  it  is  called, 
shifts  its  position  when  the  intensity  of  the  current  is  varied,  moving 
towards  the  kathode  when  the  current  is  increased,  towards  the 
anode  when  it  is  diminished. 

It  is  only  under  certain  definite  conditions  that  these  phenomena,  first 
described  by  Pfliigcr,  appear  in  their  purity  and  uncomplicated  by  other 
changes.  The  nerve  sliould  be  quite  fresh,  the  current  a  weak  or  at 
most  a  moderately  strong ^ne,  and  the  stretch  of  nerve  employed 
should  be  as  far  as  possibl^Hom  the  cross  section,  and  from  the  cross 
sections  of  branches.  The  middle  region  of  the  frog's  sciatic  nerve  is 
the  best.  When  all  these  conditions  are  fulfilled,  the  whole  stretch 
of  nerve  in  katelectrotonus — i.e.,  the  part  on  both  sides  of  the  kathode 
and  at  the  kathode  itself  shows  an  increased  stimulation  effect,  the 
more  pronounced  the  nearer  to  the  kathode  the  point  of  stimulation. 
This  condition,  however,  only  lasts  an  instant.  Then  the  excitabihty 
begins  to  sink  sharply  first  at  the  kathode,  then  on  both  sides  of  it,  till 

it  ultimately  becomes  decidedly  less  than 
the  initial  excitability.  This  secondary 
depression  of  excitability,  always  most 
marked  at  the  very  kathode,  is  just  as  con- 


Fig.  266. —  Katelectrotonus.  —  Weak 
tetanus  of  muscle  (the  right-hand 
elevation),  greatly  intensified  in 
katelectrotonus  of  the  motor  nerve 
(the  left-hand  elevation). 


Fig.  267. — Anelectrotonus.  Strong 
tetanus  of  muscle  (left-hand  ele- 
vation), lessened  in  strength  by 
anelectrotonic  condition  of  the  mo- 
tor nerve  (right-hand  elevation). 


stant  a  phenomenon  as  the  preliminary  increase.  The  stronger  the  cur- 
rent the  more  profound  is  the  depression,  the  more  quickly  1^  is  de- 
veloped, and  the  greater  is  the  distance  to  which  it  spreads  aBng  the 
nerve.  With  a  certain  strength  of  current  the  depression  apMars  so 
rapidly  that  the  preliminary  increase  of  excitability  may  be  conTfcletcly 
missed.  When  the  current  is  opened  the  excitability  quickly  ino^eascs 
again,  but  with  strong  currents  it  may  remain  depressed  for  a  while.  At 
the  anode  changes  in  the  reverse  direction  may  be  observed,  although 
they  are  less  pronounced  than  at  the  kathode.  Thus  at  the  anode 
during  the  passage  of  the  current  the  initial  depression  of  the  excitability 
tends  to  give  place  to  an  increase  (Werigo). 

These  statements  have  been  made  on  the  strength  of  experiments  in 
which  the  height  of  the  muscular  contraction  was  taken  as  the  index  of 
the  excitability  of  the  nerve  at  any  given  point.  It  is  difficult,  however, 
to  disentangle  the  effects  of  alterations  in  the  excitability  from  the 
effects  of  alterations  of  conductivity — i.e.,  of  the  power  of  a  portion  of  J 
the  nerve  to  conduct  an  impulse  set  up  elsewhere.  Whether  these  two/ 
properties  are  distinct  or  not  is  a  question  which  will  be  considered  a 
little  later  on.     But  it  is  perfectly  clear  that  in  deducing  conclusions 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     761 


as  to  the  effect  produced  on  a  nerve  by  excitation  at  a  given  point  from 
tlie  resultant  effect  on  the  muscle  to  which  the  nerve  is  attached  (or 
on  a  galvanometer  or  electrometer  if  we  are  following  the  effect  by 
m.cans  of  the  electrical  changes),  we  must  know  whether  the  change 
set  up  in  the  nerve  at  the 
point  of  excitation  can  pass 
freely  along  the  nerve  to  the 
muscle  or  to  the  point  at 
which  it  is  led  off  to  the 
galvanometer.  Now.  changes 
of  conductivity  are  certainly 
produced  in  a  nerve  by  the 
constant  current,  which  even 
outlast  its  flow.  For  all 
currents  above  a  certain 
strength  the  conductivity  at 
the  kathode  and  in  its  neigh- 
bourhood is  eventually  dim- 
inished, and  with  currents 
still  only  moderately  strong 
the  block  deepens  into  im- 
passability.  The  conduc- 
tivity at  the  anode  is,  during 
this  stage,  higher  than  at  the 
kathode,  so  that  at  the  time 
of  full  kathodic  block  tl«j 
nerve  -  impulse  still  passes 
through  the  region  around 
the  positive  pole.  With  still 
stronger  currents  the  con- 
ductivity here,  too,  dimin- 
ishes, until  the  anode  as  well 
as  the  whole  intrapolar  re- 
gion is  blocked.  After  the 
opening  of  the  current,  the 
relation  between  kathodic 
and  anodic  conductivity  is 
reversed,  for  now  the  post- 
kathodic  region  conducts  the 
nerve-impulse  relatively  bet- 
ter than  the  post -anodic.  It 
will  be  seen  that  these 
changes  of  conductivity  up- 
on the  whole  run  parallel  to 
the  (secondary)  changes  of 
excitability,  depression  of 
excitability  corresponding  to 
depression  of  conductivity, 
and  vice  versa.  With  the 
relatively  strong  currents  re- 
quired to  produce  decided 
effects  on  the  conductivity, 

any  preliminary  change  in  the  same  sense  as  the  (so-called  primary) 
effects  on  the  excitability  (increase  at  kathode,  decrease  at  anode) 
might  be  expected  to  be  fleeting,  and  thciefore  less  easy  to  detect. 

The  above  facts  serve  to  explain  the  manner  in  which  the  effects  of 
stimulation  of  a  nerve  with  the  constant  current  vary  with  the  strength 


Fig.  268. — Diagram  of  Changes  of  Excitability 
and  Conductivity  produced  in  a  Nerve  by  a 
Voltaic  Current.  E,  changes  of  excitability 
during  the  flow  of  the  current,  according  to 
Pfliiger.  These  are  seen  most  typically  with 
the  weaker  currents.  In  particular  the  in- 
creased excitability  at  and  around  the  kathode 
when  the  current  is  strong  very  quickly  gives 
place  to  depression.  The  ordinates  drawn 
from  the  abscissa  axis  to  cut  the  curve  repre- 
sent the  amount  of  the  change.  C{i),  changes 
of  conductivity  found  shortly  after  the  closure 
and  during  the  flow  of  a  moderately  strong 
current.  Conductivity  greatly  reduced  around 
kathode;  little  affected  at  anode.  C(2), 
changes  of  conductivity  during  flow  of  a  very 
strong  current.  Conductivity  reduced  both  in 
anodic  and  kathodic  regions,  but  less  in  the 
former.  C,  changes  of  conductivity  just  after 
opening  a  moderately  strong  current.  Con- 
ductivity greatly  reduced  in  region  which  was 
formerly  anodic;  little  affected  in  region  for- 
merly kathodic. 


762 


NERVE 


and  direction  of  the  stream.  These  effects,  so  far  as  the  contraction  of 
the  muscles  supplied  by  tl-ue  nerve  is  concerned,  have  been  formulated 
in  what  has  been  somewhat  loosely  termed  the  law  of  contraction.  In 
this  formula  the  direction  of  the  current  in  the  nerve  is  commonly  dis- 
tinguished by  a  thoroughly  bad  but  now  ingrained  phraseology,  as 
ascending  when  the  anode  is  next  the  muscle,  and  descending  wl>en  the 
kathode  is  next  the  muscle. 


Current. 

Ascending. 

Descending. 

M. 

B. 

C 
C 

M. 

B. 

Weak      - 
Medium  - 
Strong    - 

C 
C 

c 
c 
c 

c 

Here  M  means  '  make,'  B,  '  break,'  of  the  current;  C  means  '  con- 
traction follows.' 

The  explanation  generally  given  is  as  follows:  Wherever  there  is  an 
increase  of  excitability  sufficiently  rapid  and  sufficiently  large,  stimula- 
tion is  supposed  to  take  place;  where  there  is  a  fall  of  excitability, 
stimulation  does  not  occur.  Accordingly,  at  closure  the  kathode  stimu- 
lates— the  anode  does  not;  while  at  opening,  the  anode,  at  which  the 
depressed  excitability  jumps  up  to  normal  or  more,  is  the  stimulating 
pole;  the  kathode,  at  which  it  declines  to  normal  or  under  it,  is  inactive. 

With  a  weak  current,  (i)  contraction  only  occurs  at  make,  and  (2)  the 
direction  of  the  current  is  indifferent.  The  explanation  of  the  first  fact 
is  that  the  make  is  a  stronger  stimulus  than  the  break,  and  when  the 
current  is  weak  enough  the  break  is  less  than  a  minimal  stimulus.  No 
sensible  change  of  conductivity  is  caused  by  weak  currents,  which 
suffices  to  explain  (2). 

With  a  '  medium  '  current,  contraction  occurs  at  make  and  break  with 
both  directions.  Here  the  break  excitation  is  effective  as  well  as  the 
make.  With  anode  next  the  muscle  (ascending  current),  there  is,  of 
course,  nothing  to  prevent  the  opening  excitation,  which  starts  at  the 
anode,  from  passing  down  the  nerve  and  causing  contraction ;  and  since 
there  is  no  block  around  the  anode  or  in  the  intrapolar  region  with 
'  medium  '  currents,  there  is  nothing  to  keep  the  closing  (kathodic) 
excitation  from  reaching  the  muscle  too.  With  the  kathode  next  the 
muscle  (descending  current),  the  closing  excitation,  which  starts  from 
the  kathode,  has  no  reigon  of  diminished  conductivity  to  pass  through, 
nor  has  the  opening  (anodic)  excitation,  for  the  kathodic  block,  caused  by 
moderately  strong  currents,  is  removed  as  soon  as  the  current  is  broken. 

With  '  strong  '  currents  there  are  only  two  cases  of  contraction  out 
of  the  four,  just  as  with  '  weak,'  but  for  very  different  reasons.  There 
is  a  break-contraction  with  ascending,  and  a  make-contraction  with 
descending  current.  With  ascending  current  the  anode  is  next  the 
muscle,  and  the  break-excitation  starting  there  has  nothing  to  hinder 
its  course.  The  make-excitation,  although  as  strong  or  stronger,  has  to 
pass  through  the  whole  intrapolar  region  and  over  the  anode,  and  here 
the  conductivity  is  depressed  and  the  nerve-impulse  blocked.  With 
descending  current  the  kathode  is  next  the  muscle,  and  there  is  no 
hindrance  to  the  passage  of  the  maks-excitation.  The  break-excitation, 
however,  has  to  traverse  the  whole  intrapolar  region,  and  this  does  not 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     763 


at  onoe,  after  a  strong  current,  become  passable.     The  break-excitation, 
accordmgly,  cannot  get  through  to  the  muscle. 

A  formula  similar  to  the  law  of  contraction  has  been  shown  to  hold 
for  the  inhibitory  fibrvjs  of  the  vagus  (Bonders),  '  inhibition  '  being 
substituted  for  '  contraction.'  There  is  also  some  evidence  that  a 
similar  law  obtains  for  sensory  nerves. 

It  is  not  difficult  to  see  that  with  currents  of  brief  duration  the  break 
follows  so  quickly  on  the  make  that  interference  of  their  opposed  effects 
may  occur.  This  is  the  reason — or,  at  least,  one  reason — why,  above 
a  certain  frequency,  a  muscle  or  nerve  ceases  to  respond  to  all  of  a 
series  of  rapidly  recurring  electrical  stimuli  (p.  732).  It  is  abo  the 
reason  why,  with  single  very  brief  stimuli,  a  greater  current  intensity 
must  be  employed  in  order  to  cause  excitation  tlian  when  the  duration 
of  the  stimulating  current  is  greater  (Wood worth.  Lucas). 

The  Law  of  Contraction  for  Nerves  '  in  Situ.' — When  a  nerve  is  stimu- 
lated without  previous  isolation — in  the  human  body,  for  instance, 
through  electrodes  laid  on  the  skin — the  current  will  not  enter  and 
leave  it  through  definite  small  portions 
of  its  sheath,  nor  will  it  be  possible  to 
make  the  lines  of  flow  nearly  parallel  to 
each  other  and  to  the  long  axis  of  the 
nerve,  as  is  the  case  in  a  slender  strip  of 
tissue  when  there  is  a  considerable  dis- 
tance between  the  electrodes. 

On  the  contrary,  when,  as  is  usual  in 
electro-therapeutical  treatment,  a  single 
electrode — say,  the  positive — is  placed 
over  the  position  of  the  nerve,  and  the 
other  at  a  distance  on  some  convenient 
part  of  the  body,  the  current  will  enter 
the  nerve  by  a  broad  fan  of  stream-lines 
cutting  it  more  or  less  obliquely,  and  pass 
out  again  into  the  surrounding  tissues; 
so  that  both  an  anode  (surface  of  en- 
trance) and  a  kathode  (still  larger  surface 
of  exit)  will  correspond  to  the  single 
positive  pole.  Similarly,  the  single  nega- 
tive electrode  will  correspond  to  an 
anodic  surface  where  the  now  narrowing 


Fig.  269. — Diagram  of  Lines  of 
Flow  of  a  Current  passing 
through  a  Nerve.  A,  an  isolated 
nerve ;  B,  a  nerve  in  situ.  Secon- 
dary anodes  (  +  )  are  formed 
where  the  current  re-enters  the 
nerve  below  the  negative  elec- 
trode after  passing  through  the 
tissues  in  which  it  is  embedded 
and  secondary  kathodes  (  -  ) 
where  the  current  passes  out  of 
the  nerve  into  the  surrounding 
tissues  below  the  positive  elec- 
trode. 


sheaf  of  lines  of  flow  enters  the  nerve ,  and 
a  smaller  kathodic  surface,  where  they  emerge.  Even  if  the  two  elec- 
trodes were  on  the  course  of  the  nerve,  the  stream-lines  would  still  cut 
it  in  such  a  way  that  each  electrode  would  correspond  both  to  anode  and 
kathode  (Fig.  269). 

It  is  impossible  under  these  circumstances  to  take  account  of  the 
direction  of  a  current  in  a  nerve,  or  to  connect  direction  with  any  specific 
effect.  When  we  place  one  of  the  electrodes  over  the  nerve  and  the 
other  at  a  distance,  the  law  of  contraction  only  appears  in  a  disguised 
form;  for  since  a  kathode  and  an  anode  exist  at  each  pole,  there  is,  with 
a  current  of  sufficient  strength  ('  strong  current  '),  excitation  at  each, 
both  at  make  and  break.  The  negative  make  contraction  is.  however, 
stronger  than  the  positive,  for  the  excitation  corresponding  to  the  latter 
arises  at  the  secondary  kathodic  surface,  where  the  sheaf  of  current-lines 
spreading  from  the  positive  electrode  passes  out  of  the  nerve.  Now, 
this  is  much  larger  than  the  primary  kathodic  surface,  through  which 
the  narrow  wedge  of  stream-lines  passes  to  reach  the  negative  electrod  •. 
and  the  current  density  at  the  latter  is  accordingly  much  greater.     The 


764  NERVE 

positive  break-contraction  is,  for  a  similar  reason,  stronger  than  the 
negative. 

With  a  '  weak  '  current,  the  only  contraction  is  a  closing  one  at  the 
kathode;  with  a  '  medium  '  current  there  are  both  opening  ar  d  closing 
contractions  at  the  positive  pole,  and  a  closing  but  no  opening  con- 
traction at  the  negative  (Practical  Exercises,  p.  818). 

Conductivity  of  Nerve. — The  disturbance  which  is  called  the 
nerve-impulse,  once  set  up,  is  propagated  along  the  fibres.  Are 
the  changes  in  the  nervous  substance  involved  in  the  initiation  of 
the  disturbance  at  a  given  point  identical  with  those  involved  in 
its  transmission  from  one  point  to  the  next,  or  are  they  different  ? 
This  is  a  question  which  has  been  much  discussed,  and  many 
attempts  have  been  made  to  prove  that  the  two  processes  can  be 
dissociated  by  acting  on  nerves  with  substances  like  carbon  dioxide, 
ether,  and  alcohol,  which  gradually  suspend  their  functions,  by 
cutting  nerves  off  from  the  circulation  and  allowing  them  to  die 
gradually,  by  depriving  them  of  oxygen  and  in  other  ways.  Many  of 
the  results  obtained  from  such  experiments  seem  at  first  sight  to 
be  favourable  to  the  view  that  the  local  change  is  different  from  the 
propagated  disturbance.  Nevertheless,  careful  examination  of  the 
results  on  which  such  statements  are  based  indicates  that  none  of 
them  supplies  a  crucial  test  of  the  question  at  issue.  For  example, 
when  a  stretch  of  frog's  sciatic  nerve  is  treated  with  ether  or  another 
of  the  narcotics  which  act  on  nerve,  and  the  strength  of  stimulus 
determined  which  is  necessary  to  elicit  a  contraction  when  applied 
to  an  untreated  portion  more  remote  from  the  muscle  than  the 
narcotized  area,  this  strength  is  found,  for  some  time  after  the 
application  of  the  narcotic,  to  be  just  the  same  as  it  was  previous 
to  the  application.  '  The  conductivity  '  of  the  narcotized  stretch 
appears  to  be  unaltered.  On  the  othear  hand,  the  stimulus,  when 
applied  within  the  narcotized  region,  must  be  strengthened,  and 
the  narcotic  appears  to  have  diminished  the  '  excitability  '  of  the 
nerve.  When  the  narcotic  has  acted  for  a  longer  time,  the  reverse 
effect  appears.  No  stimulus,  however  strong,  applied  to  the  central 
non-narcotized  stretch  will  cause  a  contraction,  the  '  conductivity  ' 
having  been  apparently  totally  abolished  by  the  narcotic,  whereas 
a  strong  stimulus  applied  in  the  narcotized  region  will  still  cause 
a  contraction,  showing  that  '  excitability  '  still  remains.  As  to 
the  facts  there  is  general  agreement;  it  is  their  interpretation 
which  is  in  doubt.  Now,  it  has  been  shown  that  in  passing  along 
a  narcotized  nerve  the  propagated  disturbance  diminishes  in  pro- 
portion to  the  length  of  nerve  which  it  has  to  traverse.  Accordingly 
in  the  second  stage  of  narcosis  the  failure  of  the  stimulus  applied 
to  the  upper  part  of  the  nerve  to  elicit  a  contraction  is  explained 
most  naturally  as  due  to  the  extinction  of  the  disturbance,  which 
must  pass  through  the  whole  narcotized  region,  whereas  the  dis- 
turbance set  up  by  stimulation  in  that  region  succeeds  in  reaching 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     7O5 

the  muscle,  since  it  has  a  shorter  stretch  of  narcotized  nerve  to 
traverse.  This  experiment,  then,  in  reality  affords  no  proof  that 
excitability  and  conductivity  can  vary  independently.  Facts  are 
also  known,  to  which  allusion  need  not  be  made  here,  but  which 
greatly  modify  the  ordinary  interpretation  of  the  experimental 
results  obtained  in  the  first  stage  of  narcosis,  and  upon  the  whole 
it  may  be  said  that  these  direct  methods  of  determining  the  question 
have  failed  to  3deld  a  satisfactory  answer.  Indirect  evidence 
exists,  however,  that  the  local  process  initiated  b}'  stimulation  is 
not  quite  the  same  as  the  process  involved  in  the  propagation  of 
the  disturbance  (Lucas).  Thus,  a  brief  current  too  weak  to  set  up  a 
propagated  disturbance,  nevertheless  causes  some  change  at  the  point 
of  stimulation,  since  a  second  current,  also  too  weak  to  be  effective 
by  itself,  will,  when  thrown  in  a  short  time  after  the  first,  cause 
a  disturbance  which  is  propagated  along  the  nerve.  There  is  good 
reason  to  believe  that  the  change  produced  by  the  first  current  is 
not  the  same  in  kind  as  that  produced  by  the  second,  only  weaker, 
but  that  it  is  inherently  different  in  quality.  Above  all,  it  is  a 
local  change  incapable  of  being  itself  propagated,  but  constituting 
the  necessary  prelude  to  the  starting  of  the  propagated  disturbance. 
Lucas  has  called  this  preliminary  local  effect  the  '  local  excitatory 
process.' 

There  are  many  facts  which  indicate  that  the  capacity  of  different 
functional  or  anatomical  groups  of  nerve-fibres  for  responding  to  stimu- 
lation and  for  conducting  the  nerve-impulse  can  be  differently  affected 
by  one  and  tlie  same  influence.  For  example,  pressure  abolishes  the 
conductivity  of  sensory  fibres  sooner  than  that  of  motor  fibres. 

Cocaine  locally  applied  to  a  nerve  diminishes  or  abolishes  its  con- 
ductivity, according  to  the  dose.  It  exercises  a  selective  action  as 
regards  nerve-fibres  of  different  kinds,  picking  out  and  paralyzing 
sensory  fibres  before  motor;  vagus  fibres  conducting  upwards  before 
those  conducting  downwards,  vaso-constrictors  before  vaso-dilators, 
and  broncho-constrictors  before  broncho-dilators  (Dixcm). 

The  conduction  or  propagation  of  a  definite  disturbance  or  impulse  is 
a  phenomenon  not  confined  to  nervous  tissue.  It  is  also  characteristic- 
all}^  seen  in  muscle,  although  there  the  mechanical  effect  which  con- 
stitutes the  normal  response  to  the  arrival  of  the  propagated  disturbance 
obtrudes  itself  and  tends  to  divert  attention  from  the  latter.  It  is 
unlikely  that  the  conduction  process  m  muscle  should  be  essentially 
different  from  that  in  nerve,  and  in  muscle,  as  in  nerve,  there  is 
evidence  that  it  is  associated  with  only  a  small,  perhaps  not  even  a 
detectable,  liberation  of  heat.  The  main  heat-production  in  muscle 
is  essentially  a  feature  not  of  conduction,  but  of  contraction.  Con- 
duction in  muscle  can  be  completely  dissociated  from  the  contraction 
process  in  various  ways.  For  example,  if  a  portion  of  a  muscle  is 
immersed  for  a  time  in  distilled  water,  so-called  water  rigor  ensues,  and 
the  altered  muscle  has  lost  the  power  of  contraction.  It  will  never- 
theless conduct  the  impulse  which  on  reaching  the  unaltered  part  of  the 
muscle  causes  it  to  contract  normally. 

Double  Conduction. — When  a  nerve  (or  muscle)  is  stimulated 
artificially,  the  excitation  runs  along  it  in  both  directions  from  the 


766  NERVE 

point  of  stimulation;  so  that  nerve- fibres  which  in  the  intact  body 
are  afferent  can  conduct  impulses  towards  the  periphery  and 
efferent  fibres  can  conduct  impulses  away  from  the  periphery.  In 
the  normal  state,  however,  double  conduction  must  seldom  occur, 
for  efferent  fibres  are  connected  centrally,  and  afferent  fibres 
peripherally,  with  the  structures  in  which  their  natural  stimuli 
arise.  In  general,  too,  an  impulse,  if  it  did  pass  centrifugally  along 
an  afferent  fibre,  would  not  give  any  token  of  its  existence,  for  the 
peripheral  organ  would  not  be  able  to  respond  to  it ;  and  there  is  no 
ground  for  assuming  that  the  central  mechanisms  connected  with 
afferent  fibres  are  better  fitted  to  answer  such  foreign  and  un- 
accustomed calls  as  impulses  reaching  them  along  normally  efferent 
nerves.  There  is  good  evidence  that  muscular  excitation  is  not 
carried  over  to  the  motor  nerve- fibres;  in  other  words,  the  wave 
of  action  flows  from  the  nerve  to  the  muscle,  but  cannot  be  got 
to  flow  backwards.  Excitation  of  the  central  end  of  an  efferent 
(anterior)  spinal  root  is  not  transferred  to  the  corresponding  afferent 
(posterior)  root,  the  connection  between  the  efferent  and  afferent 
neurons  presenting  the  character  of  a  physiological  '  valve,'  which 
permits  impulses  to  pass  only  in  one  direction.  We  have  seen  that 
vaso-dilator  impulses  possibly  pass  out  to  the  limbs  over  fibres 
which,  morphologically  speaking,  are  afferent  fibres  (p.  179).  And 
we  shall  see  that  a  nutritive  influence  is  exerted  over  the  afferent 
fibres  of  the  spinal  nerves  by  the  ganglion  cells  of  the  posterior  root 
ganglia  (p.  770),  an  influence  which  must  spread  along  these  fibres 
in  the  opposite  direction  to  that  of  the  normal  excitation. 

The  best  proofs  of  double  conduction  in  nerves,  with  artificial  stimu- 
lation, are:  (i)  The  propagation  of  the  negative  variation  or  action 
current  in  both  directions.  This  holds  for  sensory  as  well  as  for  motor 
fibres,  as  du  Bois-Reymond  showed  on  the  posterior  roots  of  the  spinal 
nerves  of  the  frog  and  the  optic  nerves  of  fishes.  (2)  Stimulation  of  the 
posterior  free  end  of  the  electrical  nerve  of  Malapterurus  (p.  813)  causes 
discharge  of  the  electric  organ,  although  the  nerve-impulse  travels  nor- 
mally in  the  opposite  direction.  (3)  If  the  lower  end  of  the  frog's 
sartorius  is  split  into  two,  gentle  stimulation  of  one  of  the  tongues  causes 
contraction  of  individual  fibres  in  the  other.  This  is  supposed  to  be  due 
to  conduction  of  the  nerve-impulse  up  a  twig  of  a  nerve-fibre  distributed 
to  the  one  tongue,  and  down  another  twig  of  the  same  fibre  going  to  the 
other  tongue.  A  similar  experiment  can  be  done  on  the  gracilis  of  the 
frog.  This  muscle  is  divided  by  a  tendinous  inscription  into  two  parts, 
each  supplied  by  a  branch  of  a  nerve  which  divides  after  entering  the 
muscle.  Stimulation  of  either  twig  is  followed  by  contraction  of  both 
parts  of  the  muscle  (Kuhne). 

Bert's  much-quoted  experiment  on  the  rat  is  valueless  as  a  proof  of 
double  conduction.  He  caused  union  of  the  point  of  the  tail  with  the 
tissues  of  the  back,  then  divided  the  tail  at  the  root,  and  found  that 
stimulation  of  what  was  now  the  distal  end  caused  pain.  From  this  he 
concluded  that  the  sensory  fibres  of  the  '  transposed  '  tail  conducted 
in  the  direction  from  root  to  tip.  But  the  conclusion  is  not  warranted, 
for  sensation  disappeared  in  the  tail  after  the  section,  and  did  not 


THE  NERVE-IMPULSE  OR  PROPAGATED  DISTURBANCE     767 

return  till  some  months  later,  wken  the  nervc-fibres,  after  degenerating, 
would  have  been  replaced  by  new  sensory  fibres  growing  down  from 
the  dorsal  nerves  (Ranvier).  For  a  similar  reason  the  so-called  union 
of  the  peripheral  end  of  the  sut  hypoglossal  nerve  (motor)  with  the 
central  ^end  of  the  cut  lingual  (sensory)  proves  nothing  as  to  d»uble 
conduction,  nor  as  to  the  possibility  of  motor  nerves  taking  on  a  sensory 
function.  For  while  sensation  is  after  a  time  restored  in  the  affected 
portion  of  the  tongue,  this  is  due  to  the  growth  of  sensory  fibres  from  the 
central  stump  of  the  lingual  down  through  the  degenerated  hypoglossal, 
and  not  to  the  conduction  upwards  of  sensory  impulses  by  the  motor 
fibres  of  the  latter. 

Every  fibre  of  a  nerve  is  physiologically  isolated  from  the  rest, 
so  that  an  impulse  set  up  in  a  fibre  runs  its  course  within  it,  and 
does  not  pass  laterally  into  others  (law  of  isolated  conduction).  In 
connection  with  this  physiological  fact  there  is  the  anatomical  fact 
that  nerve-fibres  do  not  normally  branch  in  the  trunk  of  a  peripheral 
nerve.  (But  see  p.  776.)  It  has,  however,  been  shown  that  bifurca- 
tion of  nerve-fibres  may  occur  in  the  spinal  cord  (Sherrington). 
The  axis-cylinder  of  a  peripheral  nerve-fibre  only  begins  to  branch 
where  complete  isolation  of  function  is  no  longer  required,  as  within 
a  muscle.  The  expteriment  of  Kiihne  on  double  conduction,  men- 
tioned above,  shows  that  an  excitation  set  up  in  one  twig  or  one 
fibril  of  an  axis-cyhnder  which  has  branched  can  spread  to  the  rest. 

Velocity  of  the  Nerve- Impulse. — We  have  said  that  the  nerve- 
impulse  travels  with  a  measurable  velocity.  It  is  now  time  to 
describe  how  this  has  been  ascertained  (p.  791).  For  motor  fibres 
the  simplest  method  is  to  stimulate  a  nerve  successively  at  two 
points,  one  near  its  muscle,  the  other  as  far  away  from  it  as  possible, 
and  to  record  the  contractions  on  a  rapidly-moving  surface  (pendu- 
lum or  spring  myograph)  (p.  720).  The  apparent  latent  period  of 
the  curve  corresponding  to  the  nearer  point  will  be  less  than  that 
of  the  curve  corresponding  to  the  point  which  is  more  remote,  by 
the  time  which  the  impulse  takes  to  pass  between  the  two  points. 
The  distance  between  these  points  being  measured,  the  velocity  is 
known.  Helmholtz  found  the  velocity  for  frog's  nerves  at  the 
ordinary  temperature  of  the  air  to  be  a  little  under,  and  for  human 
nerves,  cooled  so  as  to  approximate  to  the  ordinary  temperature, 
a  little  over  30  metres  per  second.  For  observations  on  man  the 
contraction  curves  of  the  flexors  of  one  of  the  fingers  or  of  the 
thumb  may  be  recorded,  first  with  stimulation  of  the  brachial  plexus 
at  the  axilla,  and  then  with  stimulation  of  the  median  or  ulnar 
nerve  at  the  elbow.  Probably  at  the  same  temperature  there  is 
little  difference  in  the  rate  of  transmission  in  the  nerves  of  warm- 
blooded and  cold-blooded  animals,  but  temperature  has  a  con- 
siderable influence  (p.  756). 

By  cooling  a  frog's  nerve  Helmholtz  reduced  the  rate  to  ,\y  of  its  vaiue 
at  the  ordinary  temperature.  In  the  human  arm  he  found  a  variation 
from  30  to  90  metres  per  second,  according  to  the  temperature,  50  metres 


768  NERVE 

being  about  the  normal  rate.  This  is  greater  than  the  speed  of  the 
fastest  train  in  the  world.  According  to  Piper's  recent  measurements 
the  velocity  in  human  medullated  nerve  is  even  greater  than  Helmholtz 
concluded,  about  120  metres  a  second  under  ordinary  conditions.  The 
rate  is  independent  of  the  intensity  of  the  excitation.  The  velocity 
with  which  the  negative  variation  is  propagated  (p.  800)  is  the  same  as 
that  of  the  nerve-impulse. 

In  sensory  nerves  there  is  no  reason  to  believe  that  the  velocity  of  the 
nerve-impulse  differs  from  that  in  motor  nerves,  but  experiments  on 
man  really  free  from  objection  are  as  yet  wanting. 

The  usual  method  is  to  stimulate  the  skin  first  at  a  point  distant  from 
the  brain,  and  then  at  a  much  nearer  point.  The  person  experimented 
on,  as  soon  as  he  feels  the  stimulation,  makes  a  signal,  say,  by  closing 
or  opening  with  the  hand  a  current  connected  with  an  electric  time- 
marker,  writing  on  a  moving  surface.  There  is,  of  course,  a  measurable 
interval  between  the  excitation  and  the  signal ,  and  this  being  in  general 
longer  the  more  remote  the  point  of  stimulation  is  from  the  brain,  it  is 
assumed  that  the  excess  represents  the  time  taken  by  the  nerve-impulse 
to  pass  over  a  length  of  sensory  nerve  equal  to  the  difference  in  the 
length  of  the  path.  But  there  is  this  difficulty,  that  the  propagation 
of  the  impulse  from  the  point  of  stimulation  to  the  brain  is  only  one 
link  in  the  chain  of  events  of  which  the  signal  marks  the  end.  The 
impulse  has  first  to  be  transformed  into  a  sensation,  and  then  the  will 
has  to  be  called  into  action,  and  an  impulse  sent  down  the  motor  nerves 
to  the  hand.  And  while  the  time  taken  by  the  excitation  in  travelling 
up  and  down  the  peripheral  nerve-fibres  is  probably  fairly  constant,  the 
time  spent  in  the  intermediate  psychical  processes  is  very  variable. 


Section  II. — Chemistry,  Degeneration,  and  Regeneration  of 

Nerve. 

Chemistry  of  Nerve. — Our  knowledge  of  this  subject  is  still  scanty; 
and  most  of  what  we  do  know  has  been  obtained  from  analyses, 
not  of  the  peripheral  nerves,  but  of  the  white  matter  of  the  central 
nervous  system 

Proteins  are  present,  especially  in  the  axis-cylinder.  The  proteins  of 
nervous  tissue  include  two  globulins,  one  coagulated  by  heat  at  47°  C, 
the  other  at  70°  to  75°  C,  and  a  nucleo-protein  coagulating  at  56°  to 
60°  C. 

Very  important  constituents  are  certain  substances  soluble  in  organic 
solvents,  like  benzol  and  ether,  and  comprising  cholesterin,  certain 
phosphatides  [kephalin  and  lecithin),  and  certain  cerebrins  or  cerebrosides . 
The  cerebrins  are  glucosides  containing  nitrogen,  but  no  phosphorus, 
and  they  yield  a  reducing  sugctr  (galactose)  on  hydrolysis.  In  the 
nervous  tissue  there  is  also  present,  according  to  some  authorities,  a 
compound  called  protagon.  Others  consider  it  a  mere  mixture  of  phos- 
phatides and  cerebrosides.  The  lipoids  of  nerve-fibres  belong  largely  to 
the  medullary  sheath,  but  they  are  not  confined  to  it,  since  non-medul- 
lated  nerves  also  yield  a  considerable  quantity  of  lipoids  (11 '5  per  cent. 
of  the  solids  as  against  46-6  per  cent,  for  medullated  nerves).  Non- 
meduUated  nerves  (splenic  nerves  of  the  ox)  are  distinguished  from 
medullated  nerves  (human  sciatic)  by  the  high  proportion  of  their  total 
lipoids  constituted  by  tlie  phosphatides  (kephalin  and  lecithin)  and 
cholesterin.     Thus,  in  non-meduUated  fibres  47  per  cent,  of  the  lipoid 


CHEMISTRY  OF  NERVE  769 

G^ctract  consisted  of  cholesterin,  and  23*7  per  cent,  of  kephalin;  while 
in  the  medullatcd  fibres  cholesterin  made  up  only  25  per  cent,  of  the 
extrp.ct,  and  kephalin  12-4  per  cent.  On  the  other  hand,  the  cere- 
brosides  are  present,  both  relatively  and  absolutely,  in  much  larger 
quantity  in  meduUated  than  in  non-medullated  nerves.  In  both 
varieties  of  fibres  kephalin,  and  not  lecithin,  is  the  chief  phosphorus- 
containing  body  (Falk).  The  medullary  sheath  further  contains  a 
kind  of  network  of  a  peculiar  resistant  substance,  neurokeratin.  The 
neurilemma  consists  oi  substances  insoluble  in  dilute  sodium  hydroxide. 
Gelatin  is  obtained  from  the  connective  tissue  which  binds  the  nerve- 
fibres  together.  There  may  also  be  ordinary  fat  in  the  meshes  of  the 
epineurium  connecting  the  bundles.  Small  quantities  of  xanthin, 
hypoxanthin,  and  other  extractives,  can  also  be  obtained  from  nerve. 
According  to  Halliburton's  analyses,  the  water  in  sciatic  nerves  amounts 
to  65'i  per  cent.,  and  the  solids  to  34*9  per  cent.  The  proteins  make  up 
29  per  cent,  of  the  solids. 

For  an  analysis  of  the  white  matter  of  the  brain,  see  Chapter  XVI. 

Nerve-cells  contain  no  potassium,  according  to  Macallum;  and  this 
is  true  both  of  the  dendrites  and  the  axons.  In  medullated  nerves,  how- 
ever, potassium  compounds  are  present  external  to  the  axons,  chiefly  at 
the  nodes  of  Ranvier  (Frontispiece)  and  in  the  neurokeratin  framework 
of  the  sheath. 

The  only  chemical  difference  between  living  and  dead  nervous  tissue 
which  has  been  made  out  with  any  degree  of  certainty  is  that  the  former 
is  neutral  or  faintly  alkaline,  and  the  latter  acid,  in  reaction  to  such 
indicators  as  litmus.  This  is  especially  true  of  the  grey  matter  of  the 
central  nervous  system,  although  the  white  matter  also  is  often  found 
acid.  The  change  of  reaction  is  due  to  the  accumulation  of  lactic  acid. 
Such  a  change  has  not  hitherto  been  clearly  demonstrated  in  peripheral 
nerves,  either  after  death  or  after  prolonged  stimulation.  The  (non- 
medullated)  splenic  nerves  of  the  dog,  even  after  stimulation  for  six 
hours,  never  became  acid  (Halliburton  and  Brodie). 

Degeneration  of  Nerve. — Nerve-fibres  are  '  bound  in  the  bundle 
of  life  '  with  the  nerve-cells  from  which  their  axis-cylinders  arise; 
the  connection  between  cell  and  axon  once  severed,  the  nerve- 
fibre  dies  inevitably.  This  is  an  illustration  of  a  general  law  that 
no  portion  of  a  cell  can  live  once  it  is  separated  from  the  nucleus. 
We  shall  see  later  on  that  changes  also  occur  in  the  nerve-cell  whose 
axon  has  been  divided  from  it,  although  they  are  of  a  different 
nature  (rather  a  slow  atrophy  than  an  acute  degeneration),  and 
do  not  necessarily  lead  to  the  destruction  of  the  cell.  We  must 
regard  the  neuron  not  only  as  a  morphological  unit,  a  single  cell 
from  nucleus  to  remotest  end-brush,  but  also  as  a  functional  and 
nutritive  unit,  the  fortune  of  any  portion  of  which  is  not  in- 
different to  the  rest.  Thus,  when  a  man's  arm  is  amputated  the 
arm  fares  worse  than  the  man,  for  the  arm  dies.  But  the  man  is 
not  unaffected,  lie  lives,  but  he  suffers  much  temporary  disturb- 
ance and  some  permanent  loss.  What  is  left  of  him  is  not  quite 
the  same  as  it  was.  The  acute  changes  that  occur  in  severed  nerve- 
fibres  are  most  conveniently  studied  in  the  peripheral  nerves, 
although  essentially  similar  phenomena  take  place  also  in  the  fibres 
of  the  central  nervous  system. 

49 


770 


NERVE 


A  spinal  nerve  is  composed  of  efferent  fibres  whose  cells  of  origin 
are  in  the  grey  matter  of  the  anterior  horn,  and  afferent  fibres 
whose  cells  of  origin  are  in  the  posterior  root  ganghon.  When  such 
a  nerve  is  cut  below  the  junction  of  its  roots,  muscular  paralysis 
and  impairment  of  sensation  at  once  follow  in  the  region  supplied 
by  the  nerve;  but  for  a  time  the  nerve  remains  excitable  to  direct 

stimulation.  The  excitability 
gradually  diminishes,  and  in  a 
few  days  is  completely  gone. 
If,  portions  of  the  nerve  distal 
to  the  lesion  are  examined  at 
different  periods  after  section,  a 
remarkable  process  of  degenera- 
tion (commonly  spoken  of  as 
Wallerian  degeneration)  is  seen 
to  be  going  on.  In  the  medul- 
lated  fibres  this  begins  on  the 
second  or  third  day  with  a 
swelling  of  the  axis-cyhnder, 
which  breaks  up  into  detached 
pieces  (fragmentation),  and  as- 
sumes a  granular  appearance. 
The  medullary  sheath  also  under- 
goes fragmentation  at  the  lines 
of  Lantermann,  and  a  Httle  later 
separates  into  clumps  and  drop- 
lets of  myelin.  The  nuclei  under 
the  neurilemma  increase  in  size, 
proliferate  by  mitosis,  and  in- 
sinuate themselves  between  the 
fragments  of  the  medullary 
sheath  and  axis-cylinder,  which 
ultimately  disappear,  leaving  the 
nerve- fibre  represented  only  by  a 
kind  of  mummy  of  connective 
tissue,  in  which  the  neurilemma 
with  its  abnormally  numerous 
nuclei  can  still  be  recognized. 
The  fragmentation  of  the  myelin 
sheath  is  not  dependent  upon  the  proliferation  of  the  nuclei,  since  it 
occurs  also  in  nerves  removed  from  the  body  and  kept  under  con- 
ditions in  which  the  nuclei  do  not  prohferate  (Feiss  and  Cramer). 
The  protoplasm  around  the  nuclei  of  the  neurilemma  also  increases  in 
amount,  and  undergoes  other  changes,  which  will  be  more  particularly 
referred  to  in  describing  the  regeneration  of  nerve.  The  degenerative 
process  begins  near  the  cut  end,  and  extends  gradually  to  the  peri- 


Ur 


Fig.  270. — Degeneration  of  Nerve-Fibres 
after   Section   (Barker,   after  Tlioma). 
I,  normal  fibre;  II,  degenerating  fibre 
III,    further    stage    of    degeneration 
S,  neurilemma;  m,  medullary  sheath 
A,  axis-cylinder;  L,  Lantermann's  line 
or  cleft;  R,  node;  vit,  drops  of  myelin; 
a,  remains  of  axis-cylinder ;  w,  prolifera- 
ting cells  of  neurilemma. 


DEGENERATION  OF  NERVE 


771 


pheryi  and  more  rapidly  in  warm-  than  in  cold-blooded  animals.  At 
any  rate,  that  is  the  interpretation  generally  given  to  the  fact  that  at 
a  given  period  after  section  the  changes — especially  the  breaking- 
up  of  the  myelin — -are  more  pronounced  near  the  proximal  end  of 
the  peripheral  stump.  In  a  mammal  degeneration  is  far  advanced 
in  a  fortnight,  although  the  last  remnants  of  the  myelin  may  not 
be  absorbed  for  months.  In  the  degenerated  nerve  (cat's  sciatic) 
the  percentage  of  phosphorus  undergoes  a  diminution  from  about 
the  third  day.  About  the  eighth  day  the  loss  of  phosphorus — i.e., 
of  the  phosphatides  (lecithin,  kephalin) — is  markedly  accelerated, 
coinciding  with  the  appearance  of  a  strong  Marchi*  staining  re- 
action. By  the  twenty-ninth  day  the  degenerated  nerve  is  prac- 
tically devoid  of  phosphorus.  A  progressive  increase  in  the  water 
and  a  diminution  in  the  total  ^_..^^ 

solids  also  culminate  about  the      <CII^  K-,— ^ 

same  time  (Mott  and  Halli- 
burton). In  the  portion  of  the 
nerve-fibre  still  connected  with 
the  nerve-cell  the  degeneration 
only  extends  as  far  back  as  the 
next  node  of  Ranvier,  and  seems 
to  be  due  to  the  direct  effect  of 
the  injury.  In  non-medullated 
fibres,  such  as  the  fibres  arising 
from  the  cells  of  the  superior 
cervical  ganglion  (Tuckett),  the 
degeneration  is  confined  to  the 
axis-cylinders.  It  begins  in 
about  twenty-four  hours  after  section,  and  the  loss  of  excitability 
and  conductivity  is  complete  by  the  fortieth  hour. 

It  follows  from  what  has  been  said  as  to  the  position  of  the  cells 
of  origin  of  the  root  fibres  of  the  spinal  nerves  that  section  of 
the  anterior  root  causes  degeneration  on  the  peripheral,  but  not  on 
the  central  side  of  the  lesion,  f  Only  the  anterior  root  fibres  in  the 
mixed  nerve  degenerate.  Section  of  the  posterior  root  above  the 
ganglion  causes  degeneration  of  the  central  stump,  but  not  of 
the  portion  still  connected  with  the  ganglion,  nor  of  the  posterior 
root  fibres  below  the  ganglion  or  in  the  mixed  nerve.  Section  of 
the  posterior  root  below  the  ganglion  causes  degeneration  of  the 
fibres  of  the  root  below  the  section  and  in  the  mixed  nerve,  but  not 
above  it. 

*  The  chief  constituents  of  Marchi's  solution  are  potassium  bichromate  and 
osmic  acid.  It  stains  meduUated  nerve-fibres  black  in  the  earlier  stages  of 
degeneration. 

I  A  few  fibres  in  the  peripheral  stump  of  the  anterior  root  do  not  degenerate, 
and  a  few  fibres  in  the  central  stump  do.  Thsse  are  the  'recurrent  fibres, 
whose  course  is  described  on  p.  864. 


Fig.  271. — Degeneration  of  Spinal  Nerves 
and  their  Roots  after  Section.  The 
shadingshows  the  degenerated  portions. 


772  NERVE 

Regeneration  of  Nerve. — Degeneration  of  nerve  is  followed,  if 
its  divided  ends  are  not  kept  artificially  apart,  by  a  process  of  re- 
generation, already  distinct  under  favoui'able  conditions  in  from 
three  to  four  weeks  after  the  section,  and  indeed  in  some  cases 
commencing  as  early  as  the  second  week.  This  consists  in  the 
outgrowth  of  new  axis-cyUnders,  in  the  form  of  fine  fibres,  from 
the  ends  of  the  divided  axis-cylinders  of  the  central  stump  of  the 
nerve.  These  push  their  way  into  and  along  the  degenerated 
fibres,  ultimately  acquire  a  medullary  sheath,  and  develop  into 
complete  nerve-fibres,  restoring  first  sensation,  and  later  'on  volun- 
tary motion,  to  the  paralyzed  part.  The  process  needs  several 
months  for  its  completion,  even  in  warm-blooded  animals.  It 
takes  place  under  the  influence  of  the  nucleated  portion  of  the 
neuron  (the  cell-body),  and  is  never  completed  if  the  peripheral 
and  cenfiral  portions  of  the  nerve  are  permanently  separated  by  a 
substance  through  which  the  new  axis-cylinders  cannot  grow  or 
by  a  gap  too  wide  for  them  to  bridge  over.  When  the  'cut  ends  of 
the  nerve  are  carefully  sutured  together,  the  conditions  for  com- 
plete and  speedy  regeneration  are  rendered  more  favourable — a 
fact  which  finds  its  application  in  the  surgical  treatment  of  injured 
nerves.  The  cycle  of  chemical  changes  described  in  the  degenerating 
nerve  is  retraced  in  the  reverse  order.  In  the  cat's  sciatic  the 
first  sign  of  the  return  of  the  phosphorus  was  seen  with  the  beginning 
of  the  normal  myelin  reaction  about  the  sixtieth  day  after  section. 
At  the  one-hundredth  day  the  phosphorus  content  was  almost  as 
great  as  that  of  the  normal  nerve  (a  little  under  i  per  cent,  of  the 
solids  for  the  regenerated,  as  compared  with  a  little  over  i  per  cent, 
for  the  normal  nerve). 

It  is  not  as  yet  well  understood  how  the  regenerating  fibres  are 
directed  in  their  growth,  so  that  they  join  their  centres  to  the  appro- 
priate end-organs  without  mistake.  That  they  have  a  high  capacity 
for  finding  their  way  is  indicated  by  the  results  of  cross-suturing 
such  nerves  as  the  median  and  ulnar — i.e.,  of  uniting  the  central  end 
of  the  one  with  the  peripheral  end  of  the  other.  Howell  and  Huber 
found  that  after  this  operation  in  the  dog,  both  co-ordinated  volun- 
tary motion  and  sensation  returned  in  large  measure  in  the  parts 
supplied  by  the  nerves.  Here  the  motor  fibres  of  the  median  nerve 
must,  of  course,  have  made  connection  with  muscles  previously 
supplied  by  the  ulnar,  being  guided  to  them  along  the  nerve-sheaths 
of  the  latter.  Doubtless  the  old  nerve-sheaths  serve  to  some 
extent  as  mechanical  guides  by  offering  to  the  new  axons  a  path  of 
least  resistance.  And  when  a  nerve-trunk  containing  motor  and 
sensory  fibres  is  simply  crushed  so  as  to  destroy  all  physiological 
continuity,  but  is  not  cut,  no  distortion  of  the  motor  and  sensory 
'  patterns  '  of  the  nerve — in  other  words,  no  '  straying  '  of  the  fibres 
from  their  old  paths — can  be  detected  on  regeneration.     When  the 


REGENERATION  OF  NERVE 


773 


Fig.  272. — Regenerating  Fibres  crossing  in  the  Scar 
after  Ligation  of  a  Dog's  Sciatic  Nerve  165  Days 
previously.  Weigert-Pal  Stain.  Drawn  under  oil- 
immersion  (Feiss). 


nerve  is  cut  and  then  sutured,  a  certain  amount  of  distortion  of  the 
pattern  is  inevitable.  The  mechanical  apposition  of  central  and 
peripheral  stumps  is,  of  course,  much  more  nearly  perfect  in  the 
crushed  nerve  than  in  the  cut  nerve,  hovvevcT  exact  the  suturing 
may  be  (Osborne  and 
Kilvington).  Yet,  even 
after  crushing  or  liga- 
tion of  nerves,  or  after 
section  and  suturing, 
the  regenerating  fibres 
do  not  pass  straight 
through  the  scar  tissue 
from  the  central  to  the 
peripheral  stump,  but 
cross  and  mingle,  ap- 
parently in  the  most 
inextricable  confusion 
(Feiss)  (Fig.  272).  This 
is  due  to  the  prolifera- 
tion of  cells  in  the  scar 
which  run  in  all  direc- 
tions, and  show  no 
signs  of  following  the 
parallel  arrangement  of  the  nerve-sheaths  in  the  central  or  the 
distal  segment.  These  being  formed  before  the  regenerating 
nerve-fibres,  the  latter   must  necessarily  grow  also  in  all   direc- 

ini^/'gpw.ai    ^ ;.,  ^^^^^   in   the    scar. 

"  "        >'  \         This,  however,  is  a 
local    phenomenon. 
Beyond  the  scar  the 
arrangement  of  the 
regenerating  axis- 
cylinders     recovers 
its   regularity,   and 
the  amount  of  dis- 
tortion of  the  nerve 
pattern,  as  indicated 
by    histological   ex- 
amination    and 
functional  tests,   is 
by    no     means    so 
great   as   the   com- 
plete effacement  of  the  pattern  in  the  scar  might  appear  to  promise. 
That  the  degenerated  peripheral  stump  directs  the  growth  of 
the  axons  from  the  central  stump  in  some  other  than  a  merely 
mechanical  way  is  evident  from  the  experiments  of  Langley  on 


■^y^^ 
'     y 


Ext.     Fbpllltol  ••       ,,  ; 

Fig.  273. — Semidiagrammatic  Representation  of  Longi- 
tudinal  Section  through  Neuroma  or  Scar  produced  by 
ligating  the  Sciatic  Nerve  with  Catgut,  and  crushing  it 
with  a  hajmostat  just  above  its  Division  into  the  E.x- 
tenial  and  Internal  Popliteal  Nerves.  Weigert-Pal 
preparation  (Feiss). 


774  NERVE 

regeneration  of  the  cervical  sympathetic  in  the  cat  after  section 
below  the  superior  cervical  ganglion.  The  nerve  contains  fibres 
of  various  functions  which  reach  it  from  the  upper  thoracic  nerves. 
The  anterior  roots  of  the  first  and  third  thoracic  nerves  supply  the 
cervical  sympathetic  mainly  with  fibres  which  end  in  the  ganglion 
around  cells  that  give  off  dilator  fibres  for  the  pupil.  The  fibres 
connected  with  the  cells  in  the  ganglion  which  send  vaso-motor 
fibres  to  the  vessels  of  the  ear  are  for  the  most  part  contained  in 
the  anterior  roots  of  the  second  and  fifth  thoracic  nerves;  and  the 
fibres  connected  with  the  cells  that  give  origin  to  the  pilo-motor 
fibres  for  the  hairs  of  the  face  and  neck  in  the  anterior  roots  of  the 
fourth  to  the  seventh.  Stimulation  of  any  one  of  the  upper  thoracic 
roots  accordingly  causes  a  specific  effect,  which,  according  to 
Langley,  is  in  general  the  same  after  regeneration  as  before  section 
of  the  cervical  sympathetic.  We  must  assume,  therefore,  that  each 
regenerating  fibre  seeks  out  either  the  ganglion  cell  with  which  it 
was  originally  connected,  or  one  belonging  to  the  same  class.  No 
mere  mechanical  guidance  of  the  growing  axons  by  the  old  neuri- 
lemmas will  suffice  to  explam  this  selective  growth.  It  is  necessary 
to  postulate,  in  addition,  an  attraction  of  a  chemical  or  physico- 
chemical  nature  (chemiotaxis),  dependent  upon  a  specific  relation 
between  the  new  axons  and  the  scaffolding  of  the  peripheral  stump 
or  the  ganglion  cells.  But  it  is  not  possible  at  present  to  form  any 
very  precise  conception  of  the  properties  on  which  the  chemiotactic 
phenomena  depend.  And  the  specificity  is  not  an  absolute  one. 
Under  certain  conditions  these  pre-ganglionic  nerve-fibres  (that  is 
to  say,  nerve-fibres  running  from  the  spinal  cord  to  end  around  the 
sympathetic  ganglion  cells)  can  form  connections  with  nerve-cells 
of  a  different  class — e.g.,  pupillo-dilators  with  cells  whose  axons 
end  in  the  erector  muscles  of  the  hairs.  Further,  after  section  of 
the  sympathetic  above  the  superior  cervical  ganglion,  the  post- 
ganglionic nerve-fibres  {i.e.,  the  fibres  coming  off  from  the  cells  of 
the  ganglion)  may  also,  if  the  opportunity  be  favourable  during 
regeneration,  exchange  their  old  end-organs  for  new  ones;  pilo- 
motor fibres,  for  instance,  finding  their  way  into  the  iris  and  becoming 
pupillo-dilators.  After  excision  of  the  superior  cervical  ganglion, 
the  cervical  sympathetic  does  not  recover  its  function.  Accordingly 
the  pre-ganglionic  fibres  cannot  form  direct  functional  connection 
with  the  post-ganglionic  fibres,  but  can  become  connected  with 
them  only  indirectly  through  the  ganglion  cells.  Nor  can  efferent 
post-ganglionic  fibres  achieve  regenerative  union  with  a  cerebro- 
spinal (somatic)  motor  nerve,  although  they  can  themselves  re- 
generate, as  has  been  shown,  e.g.,  in  the  case  of  the  vaso-constrictors 
of  the  limbs.  On  the  other  hand,  union  easily  takes  place  between 
pre-ganglionic  fibres  and  efferent  somatic  fibres,  and  vice  versa. 
For  example,  the  cervical  sympathetic  can  unite  with  the  phrenic 


REGENERATION  OF  NERVE  775 

nerve,  and  cause  contraction  of  the  diaphragm,  or  with  the  recurrent 
laryngeal  nerve,  and  cause  movement  of  the  vocal  cords,  or  with 
the  spinal  accessory,  and  cause  contraction  of  the  sterno-mastoid 
muscle.  Conversely,  the  phrenic  nerve,  when  united  with  the  cer- 
vical sympathetic,  can,  when  stimulated,  produce  the  usual  effects- 
observed  on  exciting  the  latter  nerve  (Langley  and  Anderson). 

Central  and  Autogenetic  Theories  of  Regeneration. — ^Although 
the  establishment  of  connection  with  the  central  end  of  the 
cut  nerve  is  necessary  for  complete  regeneration,  it  must  not 
be  supposed  that  no  share  whatever  is  taken  in  the  process  by 
the  peripheral  stump.  Ev^en  while  it  remains  completely  isolated 
from  the  central  nervous  system,  changes  occur  which  are  often 
described  as  the  third  or  final  stage  of  degeneration,  but  which  are 
more  correctly  interpreted  as  forming  a  stage  in  the  regenerative 
cycle.  Spindle-shaped  cells  or  fibres  with  elongated  nuclei  make 
their  appearance,  produced  by  the  proliferation  of  the  nuclei  of  the 
primitive  sheath  already  described,  and  the  increase  of  the  proto- 
plasm in  which  these  nuclei  are  embedded.  These  so-called  axial 
strand  fibres  or  this  fibrillated  protoplasm  may  appear  long  before 
the  remains  of  the  degenerated  axis-cylinder  and  myelin  sheath 
have  been  completely  removed.  It  is  generally  acknowledged  that 
in  the  adult  they  do  not  develop  beyond  this,  so  long  as  the  peri- 
pheral portion  of  the  nerve  remains  completely  isolated,  but  neither 
do  they  disappear  even  after  a  very  long  interval.  When  strict 
precautions  against  union  with  other  nerve-trunks  were  taken,  the 
radial  nerve  of  an  adult  cat  was  found  in  this  resting-stage  nearly 
a  year  and  a  half  after  division,  and  the  same  was  true  after  two 
years  and  a  half  in  a  nerve  divided  in  a  human  being.  The  fibres 
are  incapable  of  being  excited  or  of  conducting  nerve  impulses. 
The  precise  relation  between  these  axial  strand  fibres  of  the  peri- 
pheral stump  and  the  mj^elinated  fibres  found  there  after  regenera- 
tion has  been  much  debated.  All  are  agreed  that  nerve-fibrils 
sprout  from  the  central  stump,  and  the  weight  of  evidence  is  in 
favour  of  the  long-accepted  view  that  it  is  by  the  growth  of  these 
fibrils  along  the  peripheral  stump  that  the  new  axons  are  formed, 
and  that  all  the  changes  in  the  distal  portion  of  the  nerve,  however 
important  for  directing  and  perhaps  sustaining  the  growth  of  the 
central  fibrils,  are  subsidiary  to  this.  But  some  maintain  that  the 
outgrowing  central  fibrils  meet  and  unite  with  corresponding  fibrils 
sprouting  from  the  peripheral  stump,  and  that  the  new  axis- 
cylinders  arise  from  the  fibrils  of  the  axial  strand.  It  is  said  that 
very  shortly  after  being  brought  into  connection  with  the  central 
portion  of  the  same  or  of  another  nerve  by  careful  suturing  the 
spindle  cells  begin  to  lengthen,  and  form  non-medullated  fibres, 
like  those  of  the  sympathetic.  Four  weeks  after  union  the  afferent 
fibres,  although  still  non-medullated,  are  capable  of  being  stimulated 


776  NERVE 

mechanically  and  elect^icall3^  and  of  conducting  impulses  towards 
the  centre.  In  about  eight  weeks  they  become  medullated,  but  at 
first  are  of  small  calibre  (Head  and  Ham).  Bet  he,  the  most  strenuous 
defender  of  the  inherent  regenerative  power  of  the  isolated  peri- 
pheral stump  (autogenetic  theory),  has  even  stated  that  complete 
regeneration  occurs  in  young  animals  in  nerves  entirely  separated 
from  their  centres.  There  is  no  doubt  that  this  result  is  due  to 
some  error  of  technique  or  of  interpretation.  The  controversy 
turns  largely  upon  the  precautions  judged  necessary  to  prevent  the 
ingrowth  of  central  fibres.  And  while  it  is  comparatively  easy  to 
make  sure,  by  removing  a  large  part  of  it,  that  the  central  end  of 
the  nerve  under  observation  shall  remain  completely  unconnected 
with  the  peripheral  end,  it  is  often  a  matter  of  the  greatest  difficulty 
to  prevent  the  union  of  the  distal  stump  with  central  fibres  from 
other  sources — e.g.,  from  the  nerves  cut  in  the  wound.  Many  of  the 
results  whidh  seemed  to  favour  the  autogenetic  theory  were  cer- 
tainly due  to  this  cause. 

The  most  conclusive  evidence  in  favour  of  central  and  against 
autogenetic  regeneration,  because  the  most  direct  and  uncompli- 
cated, has  been  afforded  by  the  demonstration  that  the  development 
of  axis-cylinders  occur  in  vitro  in  a  suitable  plasmatic  medium,  in 
the  absence  of  any  other  elements  than  the  nerve-cells  from  which 
they  arise  (Harrison).  This  observer,  working  with  the  medullary 
plates  of  tadpoles,  in  which  the  nerve-cells  originate  in  the  embryo, 
showed  further  that  peripheral  nerves  do  not  develop  when  the 
nerve-centres  are  removed,  and  that  the  sheath-cells  of  Schwann 
are  not  essential  to  the  growth  of  axis-cylinders,  since  in  their  ab- 
sence the  latter  continue  to  grow  and  reach  their  normal  length.  It 
has  also  been  proved  that  nerve-fibres  grow  out  from  pieces  of  the 
cerebellum  and  spinal  ganglia  of  young  mammals  when  cultivated  on 
clotted  plasma  outside  of  the  body  (Fig.  327,  p.  829).  ]\Iany  fibres 
sprouting  out  from  the  spinal  ganglia  attain  a  length  of  more  than 
half  a  millimetre  in  forty-eight  hours,  and  their  growth  need  not  be 
accompanied  by  either  neuroglia  or  connective  tissue  (Ingebrigtsen). 

A  fact  of  great  physiological  interest,  and  also  of  practical  impor- 
tance, in  connection  with  the  anastomosis  of  nerves  for  the  relief  of 
certain  forms  of  paralj'sis,  is  the  bifurcation  of  axons  in  regeneration, 
when  the  conditions  are  such  that  the  axons  of  the  central  stump  are 
^ffered  more  than  one  path  along  which  to  regenerate.  If,  for  instance, 
a  limb  nerve-trunk  containing  motor  fibres  is  cut,  and  its  central  end 
sutured  both  to  its  own  distal  end  and  to  the  distal  end  of  an  adjacent 
nerve-trunk,  the  sum  of  the  nerve-fibres  in  the  two  distal  trunks  after 
regeneration  has  occurred  is  greater  than  the  number  of  fibres  in  the 
central  stump  (Kilvington).  That  this  is  due  to  splitting  of  axons  is 
shown  by  the  fact  that  an  axon  reflex  (p.  883)  can  be  elicited  on  dividing 
one  of  the  distal  trunks  and  stimulating  its  central  end  after  complete 
separation  of  the  proximal  or  parent  stem  from  the  central  nervous 
system.  Even  when  the  second  path  offered  to  the  regenerating  motor 
axon  is  a  sensory  path,  bifurcation  of   the  axon  occurs,  one  branch 


DEGENERATION  OF  MUSCLE  777 

passing  down  along  the  previous  motor  path  to  its  proper  muscular 
termination,  and  the  other  passing  down  the  sensory  path.  Although 
there  is  no  evidence  that  efferent  fibres  can  unite  with  afferent  fibres,  a 
degenerated  afferent  path  can  therefore  serve  as  a  chemiotactic  scaffold- 
ing or  guide  for  the  growth  of  regenerating  motor  axons,  though  not 
such  an  efficient  one  as  a  degenerated  motor  path.  Sen.sory  fibres, 
however,  cannot  regenerate  along  motor  paths  or  make  functional  union 
with  the  receptive  substance  of  skeletal  muscle. 

Regeneration  of  the  fibres  of  the  central  nervous  system  either  does  not 
in  general  occur,  or  is  exceedingly  difficult  to  realize.  This  lends  support 
to  the  doctrine  of  the  importance  of  the  neurilemma  in  regeneration, 
since  its  elements  are  scantily  developed  in  the  fibres  of  the  brain  and 
cord  (p.  832).  Regeneration  of  the  fibres  which  proceed  from  the  cells  of 
the  spinal  ganglia  along  the  posterior  roots  into  the  cord  may  take  place 
after  the  roots  have  been  cut,  so  that  the  normal  reflexes  through  the  res- 
piratory, cardiac,  and  vaso-motor  centres  may  be  once  more  obtained. 

Degeneration  of  Muscle. — Experimental  section  or,  in  man, 
traumatic  division  or  compression  of  a  nerve  leads  not  only  to  its 
degeneration,  but  ultimately,  if  regeneration  of  the  nerve  does  not 
take  place,  to  degeneration  of  the  muscles  supplied  by  it  as  well. 
The  muscle- fibres  dwindle  to  a  quarter  of  their  normal  diameter; 
the  stripes  disappear;  the  longitudinal  fibrillation  fades  out;  and  at 
length  only  hyaline  moulds  of  the  fibres  are  left,  filled,  and  separated 
by  fatty  granules  and  globules  and  surrounded  by  engorged  capil- 
laries. Amidst  the  general  decay,  the  muscular  fibres  of  the 
terminal  '  spindles  '  with  which  the  afferent  nerves  of  muscles  are 
connected  alone  remain  unchanged  (Sherrington).  Certain  dis- 
eases of  the  cord  which  interfere  with  the  cells  of  the  anterior  horn 
cause  degeneration  of  motor  nerves,  and  ultimately  of  muscles. 
The  motor  nerve-endings  degenerate  sooner  than  the  sensory. 
Both  may,  under  suitable  conditions,  regenerate  (Huber). 

Reaction  of  Degeneration. — ]\Iuscles  whose  motor  nerves  have  been 
separated  from  their  trophic  centres  show,  when  a  certain  stage  in 
degeneration  has  been  reached,  a  peculiar  behaviour  to  electrical 
stimulation,  called  the  '  reaction  of  degeneration.'  To  the  constant 
current  the  muscles  are  more  excitable,  and  the  contraction  slower  and 
more  prolonged  than  normal.  When  a  current,  either  constant  or 
induced,  is  passed  through  a  normal  muscle,  the  muscular  fibres  may  be 
stimulated  either  directly,  or  indirectly  through  the  intramuscular 
nerves.  Under  ordinary  conditions  the  nerves  respond  more  readily 
than  the  muscular  fibres,  especially  to  momentary  stimuli  like  induction 
shocks,  and  therefore  the  so-called  direct  stimulation  of  uncurarized 
muscle  is  as  a  rule  an  indirect  stimulation.  When  the  muscle  is 
curarized  and  the  nerves  thus  eliminated,  the  excitability  to  induced 
currents  is  found  to  be  diminished.  The  same  is  the  case  in  a  muscle 
which  exhibits  the  reaction  of  degeneration  after  section  of  its  motor 
nerve,  only  the  loss  of  excitability  to  induced  currents  is  greater,  and 
may  even  be  complete.  The  common  statement  that  the  closing  anodic 
contraction  is  stronger  than  the  closing  kathodic — the  opposite  of  the 
ordinary  law — is  subject  to  so  many  exceptions  that  it  has  no  diagnostic 
value.  The  nerves  are  inexcitable  either  to  constant  or  induced 
currents.  The  reaction  of  degeneration  is  only  obtained  from  paralyzed 
muscles  when  the  paralyzing  lesion  is  situated  in  the  cells  of  the  anterior 


778  NERVE 

horn  trom  which  the  motor  nerves  take  origin,  or  below  that  level. 
Accordingly,  it  is  sometimes  of  use  in  localizing  the  position  of  a  lesion. 
For  instance,  a  group  of  muscles  might  be  paralyzed  by  a  lesion  in  the 
grey  matter  of  the  brain  or  in  the  nerve-fibres  connecting  this  with  the 
grey  matter  of  the  anterior  horn  of  the  cord,  or  in  the  grey  matter  of 
the  anterior  horn  itself,  or  in  the  peripheral  nerve-fibres  leading  from 
this  to  the  muscles.  In  the  first  two  cases  the  reaction  of  degeneration 
would  be  absent,  although  the  muscles,  if  the  lesion  was  of  long  standing, 
would  be  atrophied  to  some  extent;  in  the  last  two  there  would  be  acute 
atrophy  of  the  muscles,  and  the  reaction  of  degeneration  would  be 
obtained. 

Trophic  Nerves. — There  is  no  question  that  nerves  exert  a  very 
important  influence  upon  the  nutrition  of  the  parts  supphed  b}' 
them,  in  influencing  the  specific  function  of  those  parts.  So  that 
in  this  sense  all  nerves  are  trophic  nerves.  The  fact  that  the  proper 
nutrition  of  nerve-fibres  and  striated  muscular  fibres  is  dependent 
on  their  connection  with  nerve-cells  has  been  by  some  writers 
generalized  into  the  doctrine  that  all  tissues  are  provided  with 
'  trophic  '  nerves,  which,  apart  from  any  influence  of  functional 
activity,  regulate  the  nutrition  of  the  organs  they  supply.  But  the 
evidence  for  this  view,  when  weighed  in  the  balance,  is  found 
wanting;  and  it  may  be  said  that  up  to  the  present  no  unequivocal 
proof,  experimental  or  clinical,  has  ever  been  given  of  the  existence  of 
specific  trophic  fibres,  anatomically  distinct  from  other  efferent  or 
afferent  nerves. 

It  is  true  that  in  various  diseases  and  injuries  of  the  nervous  system 
nutritive  changes  in  the  skin,  and  sometimes  in  the  bones  and  joints, 
are  apt  to  appear.  But  it  is  very  difficult  in  such  cases  to  disentangle 
the  effects  produced  by  accidental  injuries  acting  on  structures  whose 
normal  sensibility  is  lost  or  lessened,  or  whose  circulation  is  deranged, 
from  true  trophic  changes.  The  most  that  can  be  said  is  that  there  is 
some  evidence  that  the  power  of  the  skin  to  resist  injury, "and  the 
capacity  of  recovering  from  it,  are  diminished  by  interference  with  its 
nerve-supply,  so  that  a  large  sore  may  result  from  a  trifling  lesion,  and 
healing  may  be  slow  and  difficult.  Experimentally  it  has  been  found 
that  division  of  the  trigeminus  nerve  within  the  skull  is  sometimes 
followed  by  cloudiness  of  the  cornea,  going  on  to  ulceration,  and  ulti- 
mately inflammation  and  destruction  of  the  eyeball.  Ulcers  also  form 
on  the  lips  and  on  the  mucous  membrane  of  the  mouth  and  gums ;  and 
the  nasal  mucous  membrane  on  the  side  corresponding  to  the  divided 
nerve  becomes  inflamed.  But  in  this  case  the  sensibility  of  the  eye  is 
lost,  and  reflex  closure  of  the  eyelids  ceases  to  prevent  the  entrance  of 
foreign  bodies.  The  animal  is  no  longer  aware  of  the  contact  of  particles 
of  dust  or  bits  of  straw  or  accumulated  secretion  with  the  conjunctiva, 
and  makes  no  effort  to  remove  them.  The  lips,  being  also  without 
sensation,  are  hurt  by  the  teeth,  particularly  as  the  muscles  of  mastica- 
tion on  the  side  of  the  divided  nerve  are  paralyzed,  and  decomposed 
food,  collecting  in  the  mouth,  and  inhaled  dust  in  the  nose,  will  tend 
still  further  to  irritate  the  mucous  membranes.  There  is  thus  no  more 
need  to  assume  the  loss  of  unknown  trophic  influences  in  order  to 
explain  the  occurrence  of  the  ulcerative  changes  than  there  is  to 
explain  the  production  of  ordinary  bed-sores,  bunions  or  corns  on  parts 
peculiarly  liable  to  pressure.     And,  as  a  matter  of  fact,  if  tlie  eye  be 


TROPHIC  NERVES  779 

artificially  protected,  after  section  of  the  trigeminal  nerve,  the 
ophthalmia  either  does  not  occur  or  is  much  delayed. 

In  man,  too,  a  case  has  been  recorded  in  which  both  the  fifth  and 
the  third  nerves  were  paralyzed.  The  eye  was  still  shielded  by  the 
contraction  of  the  orbicularis  oculi  supplied  by  che  seventh  nerve,  as 
well  as  by  the  drooping  of  the  upper  eyelid  that  accompanies  paralysis 
of  the  third.  It  remained  perfectly  sound  for  many  months,  till  at 
length  the  tumour  at  the  base  of  the  brain  which  had  affected  the  other 
nerves  involved  the  seventh  too.  The  eye  was  now  no  longer  com- 
pletely closed;  inflammation  came  on,  and  vision  was  soon  permanently 
lost  (Shaw).  In  another  case  a  patient  lived  for  seven  years  with 
complete  paralysis  of  the  fifth  nerve,  yet  the  eye  remained  free  from 
disease  and  sight  was  unimpaired  (Gowcrs). 

The  so-called  '  trophic  '  effects  following  division  of  both  vagi  we 
have  already  discussed  (p.  280)  so  far  as  they  are  concerned  with  the 
respiratory  system.  The  degenerative  changes  sometimes  seen  in  the 
heart  are  perhaps  due  to  its  being  overworked  in  the  absence  of  nervous 
restraint  on  its  functional  activity.  The  nutritive  alterations  in 
muscles  and  salivary  glands  after  section  of  motor  and  secretory  nerves 
seem  to  depend  in  part  on  functional  and  vaso-motor  changes.  In  the 
paralyzed  muscles  nutrition  is  not  only  interfered  with  in  consequence 
of  their  inactivity,  as  would  be  the  case  even  if  the  paralysis  were  due 
to  a  lesion  above  the  level  of  the  anterior  comual  cells,  but  the  already 
poorly  nourished  fibres  are  continually  pressed  upon  by  the  capillaries, 
which  are  dilated  owing  to  the  division  of  the  vaso-motor  nerves.  The 
degeneration  must  also  be  in  part  ascribed  to  the  loss  of  a  tonic  influence 
exerted  on  the  muscles  by  the  motor  cells  of  the  spinal  cord,  through  the 
ordinary  motor  nerves  (p.  889).  When  all  allowance  has  been  made  for 
these  factors,  the  rapid  and  characteristic  degeneration  of  the  striated 
muscles,  after  their  connection  with  the  central  nervous  system  is 
severed,  is  still  inexplicable,  except  on  the  assumption  that  their 
nutrition  is  specially  related  to  the  ir^tegrity  of  their  efferent  nerves. 
In  other  words,  it  is  necessary  to  suppose,  not,  indeed,  that  distinct 
trophic  nerves  exist  for  the  muscles,  but  that  an  influence  or  impulses, 
which  can  be  termed  trophic  or  nutritive,  do  normally  pass  out  to  them 
from  the  spinal  cord  along  their  motor  nerves. 

Section  of  the  cervical  sympathetic  in  young  rabbi  ts  and  dogs  increases 
the  growth  of  the  ear  and  of  the  hair  on  the  same  side.  But  it  is 
impossible  to  separate  these  consequences  from  the  vaso-motor  paral- 
ysis ;  and  the  same  is  true  of  the  hypertrophy  following  section  of  the 
vaso-motor  nerves  of  the  cock's  comb  and  of  the  nerves  of  the  bones. 
After  section  of  the  superior  laryngeal  the  vocal  cord  on  the  side  of  the 
section  is  at  once  rendered  motionless,  and  remains  so,  but  the  muscles, 
notwithstanding  their  inaction,  do  not  degenerate.  And  Mott  and 
Sherrington  have  found  that,  although  section  of  the  posterior  roots  in 
monkeys  is  followed  after  a  time  (three  weeks  to  three  months)  by 
ulceration  over  certain  portions  of  the  foot,  no  corresponding  lesions 
occur  in  the  hand.  They  believe,  therefore,  that  the  lesions  are  not  due 
to  the  withdrawal  of  a  reflex  trophic  tone,  but  are  accidental  injuries 
in  positions  specially  exposed  to  mechanical  or  microbic  insults. 

One  of  the  best  examples  of  interference  with  the  proper  nutrition  of 
a  part  produced  by  a  lesion  in  the  nerves  supplying  it  is  an  eruption 
(herpes  zoster),  limited  to  the  skin  supplied  by  the  nerve-fibres  coming 
from  one  or  more  spinal  ganglia,  and  depending  on  an  (infectious) 
inflammatory  change  in  the  ganglia.  It  has  been  suggested  that  the 
vesicles  are  formed  cither  because  the  passage  of  afferent  impulses 
normally  concerned  in  the  nutrition  of  the  skin  is  interfered  with  or 


78o 


NERVE 


of 


because  the  skin  is  bombarded  by  antidromic  (p.  179)  impulses  dis- 
charged from  the  inflamed  ganglia.  But  an  alternative  hypothesis  is 
that  a  toxine  spreads  out  along  the  nerves  from  the  ganglia,  just  as 
in  traumatic  tetanus  the  toxine  is  known  to  pass  in  the  opposite  direc- 
tion along  the  nerves  from  the  seat  of  injury  to  the  central  nervous 
sj^stem. 

Classification  of  Nerves. — Omitting  the  group  of '  trophic  '  nerves, 
and  the  even  more  problematical '  thermogenic  '  fibres  (which  some 
have  supposed  to  preside  over  the  production  of  heat,  and  therefore 
to  assist  in  the  regulation  of  the  temperature  of  the  body,  but  of 
whose  existence  as  distinct  and  specific  nerve-fibres  with  no  other 
function  there  is  not  the  slightest  proof),  peripheral  nerves  may  be 
classified  as  follows: 

f  Smell. 
Nerves  of  special  sensation  -|  bearing 

i  Sight. 

''  Touch  (light  touch). 
Pressure      (perhaps 

,,  ,  1  ,•  eluding  the    nerves 

Nerves  of  general  sensation  -       ^^^^^f^,  ,^^3^) 

Warmth — Cold . 

Pain. 

Calibre  of  small  arteries 
(pressor,  depressor). 

Action  of  heart. 

Respiratory  movements. 

Visceral  movements. 

Glandular  secretion. 

Ordinary      skeletal 
muscles. 
Skeletal  muscles 
Visceral 

,,  ,  r         -ir  ^„  1  „  r  Vaso-constrictor 

1.  Motor  nerves  for -^  Vascular      ,,        \  n     ^-  *. 
I                                 I  Cardio-augmentor. 

Erector  muscles  of  hairs  (pilo-motor 

\^      fibres). 

(  Visceral  muscles 

2.  Inhibitory  nerves  for  \  f  Vaso-dilator. 
{ Vascular       ,,        '.  Cardio-inhibi- 

^  3.  Secretory  nerves  [      tory. 

*  It  is  not  known  whether  the  afferent  portion  of  a  reflex  arc  is  always  com- 
posed of  fibres  included  in  the  lirst  two  categories,  although  undoubtedly  in 
some  cases  it  is. 


Centripetal 
or    afferent  ' 
fibres. 


3.*  Possibly  nerves  other  than 
those  included  under  i 
and  2,  concerned  in 
reflex  changes  in 


Centrifugal 

or    efferent 

fibres. 


PRACTICAL  EXERCISES  ON  CHAPTERS  XIII.  AND  XIV. 

I.  Difference  of  Make  and  Break  Shocks  from  an  Induction  Machine. 

— Connect  a  Daniell  or  other  cell  B  (p.  Gijy)  with  the  two  upper  binding- 
screws  of  the  primary  coil  P,  and  interpose  a  spring  key  K  in  the  circuit. 
Connect  a  pair  of  electrodes  with  the  binding-screws  of  the  secondary 
coil  (Fig.  274). 


PRACTICAL  EXERCISES 


781 


Electrodes  can  be  verj'  simply  made  by  pushing  copper  wires  through 
two  glass  tubes,  filling  the  ends  of  the  tubes  with  sealing-wax.  and 
binding  them  together  with  waxed  thread.  The  projecting  points  may 
be  filed,  and  the  nerve  laid  directly  on  them,  or  they  may  be  tipped  with 
small  pieces  of  platinum  wire  soldered  on. 

(a)  Push  the  secondary  away  from  the  primary,  until  no  shock  can 
be  felt  on  the  tongue  when  the  current  from  the  battery  is  made  or 
broken  with  the  key.  Then  bring  the  secondary  gradually  up  towards 
the  primary,  testing  at  every  new  position  whether  the  shock  is  per- 
ceptible. It  will  be  felt  first  at  break.  If  the  secondary  is  pushed  still 
further  up,  a  shock  will  be  felt  both  at  make  and  at  break.  From  this 
we  learn  that  for  sensory  nerves  the  break  shock  is  stronger  than  the 
make.  The  same  can  easily  be  demonstrated  for  motor  nerves  and 
for  muscle. 

(b)  Smoke  a  drum  and  arrange  a  myograph,  as  shown  in  Fig.  278. 
But  omit  the  brass  piece  F,  and  do  not  connect  the  primary  through 
the  drum,  as  there  shown,  but  connect  it  as  in  Fig.  274.  Pith  a  frog 
(brain  and  cord),  and  make  a  muscle-nerve  preparation. 

To  make  a  Muscle-Nerve  Preparation. — Hold  the  frog  by  the  hind  legs 
back  upwards;  the  front  part  of  the  body  will  hang  down,  making  an 
angle  with  the  posterior 
portion.  With  strong 
scissors  divide  the  back- 
bone anterior  to  this 
angle,  and  cut  away  all 
the  front  portion  of  the 
body,  which  v.ill  fall 
down  of  its  own  weight. 
Make  a  circular  incision 
at  the  level  of  the  tendo 
Achillis,  and  another  at 
the  lower  end  of  the 
femur,  through  the  skin. 
The  sciatic  nerve  must 
now  be  dissected  out,  as 
follows:  Remove  the 
skin  from  the  thigh,  and, 

holding  the  leg  in   the  ^         ,        ,    •  a.         1 

left  hand  slit  up  the  fascia  which  connects  the  external  and  mtemal 
groups  of  muscles  on  the  back  of  the  thigh.  Complete  the  separa- 
tion with  the  two  thumbs.  Cut  through  the  iliac  bone,  takmg 
care  that  the  blade  of  the  scissors  is  well  pressed  agamst  the  bone, 
otherwise  there  is  danger  of  severing  the  sciatic  plexus.  Now  divide 
in  the  middle  line  the  part  of  the  spinal  column  which  remains  above 
the  urostyle.  A  piece  of  bone  is  thus  obtained  by  means  of  which  the 
nerve  can  be  manipulated  without  injury.  Seize  this  piece  of  bone  with 
the  forceps,  and  carefully  free  the  sciatic  plexus  and  nerve  from  their 
attachments  right  down  to  the  gastrocnemius  muscle,  taking  care  not 
to  drag  upon  the  nerve.  The  muscles  of  the  thigh  will  contract,  as  the 
branches  going  to  them  are  cut.  This  is  an  instance  of  mechanical 
stimulation.  Now  pass  a  thread  under  the  tendo  Achillis,  tie  it,  and 
divide  the  tendon  below  it.  Strip  up  the  tube  of  skin  that  covers  the 
gastrocnemius,  as  if  the  finger  of  a  glove  were  being  taken  off.  Tear 
through  the  loose  connective  tissue  between  the  muscle  and  the  bones 
of  the  leg.  and  divide  the  latter  with  scissors  just  below  the  knee.  Cut 
across  the  thigh  at  its  middle.  ,.  ,  .  , 

Fix  the  preparation  on  the  cork  plate  of  the  myograph  by  a  pm  passed 


Fig.  274. — Arrangement  of  Coil  for  Single  Shocks. 


782 


MUSCLE  AND  NERVE 


through  the  cartilaginous  lower  end  of  the  femur,  and  attach  the 
thread  to  the  upright  arm  of  the  lever  by  one  of  the  holes  in  it.  Hang 
not  far  from  the  axis  by  means  of  a  hook  a  small  leaden  weight  (5  to 
10  grammes)  on  the  arm  of  the  lever  which  carries  the  writing-point, 
and  move  the  myograph  plate  or  the  muscle-nerve  preparation  until 
this  arm  is  just  horizontal.  Fasten  the  electrodes  from  the  secondary 
coil  on  the  cork  plate  with  an  indiarubber  band ;  lay  the  nerve  on  them ; 
and  cover  both  muscle  and  nerve  with  an  arch  of  blotting-paper 
moistened  with  physiological  salt  solution,  taking  care  that  the  blotting- 
paper  does  not  touch  the  thread.  Or  put  the  preparation  in  a  moist 
chamber*  ^Fig.  312,  p.  815).     Muscle  troughs  of  various  kinds  may  also 


Fig.  275. — Lucas's  Muscle  Trough.  A,  trough  made  ot  hard  rubber;  B,  a  hard  rubber 
boss  with  a  hole  drilled  in  it  to  receive  the  pin  which  fastens  the  gastrocnemius 
preparation;  H,  H,  electrodes  cased  in  hard  rubber  except  at  the  ends,  which 
in  the  trough  carry  platinum  wires;  C,  a  brass  plate  mounted  on  one  side  of  the 
trough,  carrying  a  lever  with  a  vertical  arm  F  ending  in  a  hook,  which  is  attached 
by  a  loop  of  thread  to  the  tendon  of  the  preparation ;  G.  the  writing  arm  of  the 
lever;  K,  M,  holes  in  G  for  loading  the  muscle.  C  can  be  slid  horizontally  by 
means  of  the  slots  in  it,  and  clamped  by  the  screw  E.  I,  tube  for  running  off 
the  solution. 


be  used,  which  permit  immersion  of  a  muscle  (or  nerve)  in  Ringer's 
solution.  A  convenient  form  is  shown  in  Fig.  275,  but  a  trough  suffi- 
cient for  the  purposes  of  the  student  can  be  easily  improvised  in  any 
laboratory.  Adjust  the  v/riting-point  to  the  drum.  Begin  with  such 
a  distance  between  the  coils  that  a  break  contraction  is  just  obtained 
on  opening  the  key  in  the  primary  circuit,  but  no  make  contraction. 
The  lever  will  trace  a  vertical  line  on  the  stationary  drum.  Read  off 
on  the  scale  of  the  induction  machine  the  distance  between  the  coils, 
and  mark  this  on  the  drum.  Now  allow  the  drum  to  move  a  little,  still 
keeping  the  writing-point  in  contact  with  it ;  then  push  up  the  secondary 
coil  I  centimetre  nearer  the  primary,  and  close  the  key.     If  there  is  a 

•  Porter's  moist  chamber  is  found  in  many  laboratories,  and  is  very  con- 
venient. It  consists  of  a  porcelain  plate  around  which  runs  a  groove.  A  bell- 
shaped  glass  cover,  which  can  be  lifted  off  at  will,  rests  in  the  groove.  The 
femur  of  the  rausclc-nerve  preparation  is  fixed  in  a  small  clamp,  composed 
of  a  split  screw  on  which  moves  a  nut.  By  means  of  the  nut  the  clamp  is 
tightened  on  the  femur.  The  gastrocnemius  hangs  vertically  down,  the  thread 
on  the  tendo  Achillis  passing  through  a  hole  in  the  porcelain  plate  to  a  lever 
separately  supported  on  the  same  stand  as  the  moist  chamber.  A  piece  of 
wet  blotting-paper  fixed  inside  the  cover  keeps  the  air  in  the  chamber  saturated. 


PRACTICAL  EXERCISES 


783 


contraction,  let  the  drum  move  a  little  before  opening  the  key  again, 
so  that  the  lines  corresponding  to  make  and  break  may  be  separated 
from  each  other.  If  there  is  still  no  contraction  at  make,  go  on  moving 
the  secondary  up,  a  centimetre  (or  less)  at  a  time,  till  a  make  con- 
traction appears.  When  the  coils  are  still  further  approximated,  the 
make  may  become  equal  in  height  to  the  break  contraction,  both  being 
maximal — i.e.,  as  great  as  the  muscle  can  give  with  any  single  shock 
(Fig.  276). 

(c)  Attach   a  thin  insulated   copper  wire  to  each  terminal  of  the 
secondary.     Loop  the  bared  end  of  one  of  the  wires  through  the  tendo 


I 

JJ__LI Ll 

MB      WB       MB 
22        90         IS 


i__i. 


I-"ig.  276. — Contractions  caused  by  Make  and  Break  Shocks  from  an  Induction 
Machine.  M,  make,  B,  break,  contractions.  The  numbers  give  the  distance 
between  the  primary  and  secondary  coils  in  centimetres. 

Achillis,  and  coil  the  other  round  the  pin  in  the  femur,  so  that  the  shocks 
will  pass  through  the  whole  length  of  the  muscle.  Repeat  the  experi- 
ment of  {b),  with  direct  stimulation  of  the  muscle. 

2.  Stimulation  of  Nerve  and  Muscle  by  the  Voltaic  Current. — (a)  Con- 
nect a  Danicll  cell  through  a  key  with  a  pair  of  electrodes  on  which  the 
nerve  of  a  muscle-nerve  preparation  lies.  Observe  that  the  muscle  con- 
tracts when  the  current  is  closed  or  broken,  but  not  during  its  passage. 


Fig.  277.  Simple  Rheocord  arranged  to  send  a  Twig  of  a  Current  through  a  Muscle 
or  Nerve.  B,  battery;  R,  rheocord  wire  (German  silver);  S,  slider  formed  of 
a  short  piece  of  thick  indiarubber  tubing  filled  with  mercury;  K,  spring  key; 
\V,  W,  wires  connected  with  electrodes. 


Connect  the  cell  with  a  simple  rheocord,  as  shown  in  Fig.  277,  so  that 
a  twig  of  the  current  of  any  desired  strength  may  be  sent  through  the 
nerve.  As  the  strength  of  the  current  is  decreased  by  moving  the 
slider  S,  it  will  be  found  that  it  first  becomes  impossible  to  obtain  a ' 
contraction  at  break.  The  current  must  be  still  further  reduced  before  ' 
tho  make  contraction  disappears,  for  the  closing  of  a  galvanic  stream 
is  a  stronger  stimulus  than  the  breaking  of  it.     The  break  or  make  con- 


784  MUSCLE  AND  NERVE 

traction  obtained  bj?-  stimulating  a  neive  with  an  induction  machine 
must  not  be  confused  witli  the  break  or  make  contraction  caused  by  the 
voltaic  current.  In  the  case  of  the  induction  machine,  the  break  or 
make  applies  merely  to  what  is  done  in  the  primary  circuit,  not  to  what 
happens  to  the  current  actually  passing  through  the  nerve.  The 
current  induced  in  the  secondary  at  make  of  the  primary  circuit  is,  of 
course,  both  made  and  broken  in  the  nerve — made  when  it  begins  to 
flow,  broken  when  the  flow  is  over;  the  shock  induced  at  break  of  the 
primary  is  also  made  and  broken  in  the  nerve.  And  although  make  and 
break  of  the  actual  stimulating  current  come  very  close  together,  the 
real  make,  here,  too,  is  a  stronger  stimulus  than  the  real  break. 

{b)  Repeat  {a)  with  the  muscle  directly  connected  to  the  cell  by  thin 
copper  wires,  or,  better,  unpolarizable  electrodes  (p.  705). 

3.  Ciliary  Motion. — Cut  away  the  lower  jaw  of  the  same  frog,  and 
place  a  small  piece  of  cork  moistened  with  physiological  salt  solution 
(o*75  per  cent.)  on  the  ciliated  surface  of  the  mucous  membrane  covering 
the  roof  of  the  mouth.  It  will  be  moved  by  the  cilia  down  towards  the 
gullet.  Lay  a  small  rule,  divided  into  millimetres,  over  the  mucous 
membrane,  and  measure  with  a  stop-watch  the  time  the  piece  of  cork 
takes  to  travel  over  10  millimetres.  Then  pour  salt  solution  heated  to 
30°  C.  on  the  ciliary  surface,  rapidly  swab  with  blotting-paper,  and 
repeat  the  observation.  The  piece  of  cork  will  now  be  moved  more 
quickly  than  before,  unless  the  salt  solution  has  been  so  hot  as  to  injure 
the  ciha. 

4.  Direct  Excitability  of  Muscle — Action  of  Cnrara. — Pith  the  brain 
of  a  frog,  and  prevent  bleeding  by  inserting  a  piece  of  match.  Expose 
the  sciatic  nerve  in  the  thigh  on  one  side.  Carefully  separate  it,  for  a 
length  of  half  an  inch,  from  the  tissues  in  which  it  lies.  Pass  a  strong 
thread  under  the  nerve,  and  tie  it  tightly  round  the  limb,  excluding 
the  nerve.  Now  inject  into  the  dorsal  or  ventral  lymph-sac  a  few  drops 
of  a  I  per  cent,  curara  solution.  As  soon  as  paralysis  is  complete,  make 
two  muscle-nerve  preparations,  isolating  the  sciatic  nerves  right  up  to 
the  vertebral  column.  Lay  their  upper  ends  on  electrodes  and  stimu- 
late; the  muscle  of  the  ligatured  limb  will  contract.  This  proves  that 
the  nerve-trunks  are  not  paralyzed  by  curara,  since  the  poison  has  been 
circulating  in  them  above  the  ligature.  The  muscle  of  the  leg  which 
was  not  ligatured  will  contract  if  it  be  stimulated  directly,  although 
stimulation  of  its  nerve  has  no  effect.  The  ordinary  contractile  sub- 
stance of  the  muscular  fibres,  accordingly,  is  not  paralyzed.  The  seat 
of  paralysis  must  therefore  be  some  structure  or  substance  physiologic- 
ally intermediate  between  the  nerve-trunk  and  the  general  contractile 
substance  of  the  muscular  fibres  (p.  712). 

5.  Graphic  Record  of  a  Single  Muscular  Contraction  or  Twitch. — Pith 
a  frog  (brain  and  cord),  make  a  muscle-nerve  preparation,  and  arrange 
it  on  the  myograph  plate,  as  in  i  [b).  Lay  the  nerve  on  electrodes 
connected  with  the  secondary  coil  of  an  induction  machine  arranged 
for  single  shocks.  Introduce  a  short-circuiting  key  (Fig.  232,  p.  706) 
between  the  electrodes  and  the  secondary  coil,  and  a  spring  key  in  the 
primary  circuit.  Close  the  short-circuiting  key,  and  then  press  down 
the  spring  key  with  the  finger.  Let  the  drum  off  (fast  speed) ;  the 
writing-point  will  ti"ace  a  horizontal  abscissa  line.  Open  the  short- 
circuiting  key,  and  then  remove  the  finger  from  the  spring  key.  The 
nerve  receives  an  opening  shock,  and  the  muscle  traces  a  curve.  Now 
adjust  the  writing-point  of  an  electrical  tuning-fork  (Fig.  278),  vibrating, 
say,  100  times  a  second,  to  the  drum,  and  take  a  time-tracing  below  the 
muscle-curve.  Stop  the  drum,  or  take  off  the  writing-point,  the 
moment  the  time-tracing  has  completed  one  circumference  of  the  drum, 


PRACTICAL  EXERCISES  785 

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each  vihratmn  of  the  fork,  the  date,  and  the  name  of  the  maker  of  tho 

by      IcrVtruSl'th:-     A^=»'='ly--ila^  tracing  ca'Ce  obtain  d 
y  uirtcciy  stimuJatmg  the  muscle  (curarizcd  or  not). 

50 


786  MUSCLE  AND  NERVE 

6.  Influence  of  Temperature  on  the  Muscle-Curve. — Pith  a  frog  (brain 
and  cord),  make  a  muscle-nerve  preparation,  and  arrange  it  on  a 
myograph.  Lay  the  nerve  on  electrodes  connected  through  a  short- 
circuiting  key  with  the  secondary  coil  of  an  induction  machine,  or 
connect  the  muscle  directly  with  the  key  by  thin  copper  wires.  Take 
a  Daniell  cell,  connect  one  pole  through  a  simple  key  with  one  of  the 
upper  binding-screws  of  the  primary  coil,  and  the  other  pole  with  the 
metal  of  the  drum.  A  wire,  insulated  from  the  drum,  but  clamped  on 
the  vertical  part  of  its  support,  and  with  its  bare  end  projecting  so  as 
to  make  contact  with  a  strip  of  brass  fastened  on  the  spindle,  is  con- 
nected with  the  other  upper  terminal  of  the  primary  (Fig.  278).  At 
each  revolution  of  the  drum  the  primary  circuit  is  made  and  broken 
once  as  the  strip  of  brass  brushes  the  projecting  end  of  the  wire.  The 
object  of  this  arrangement  is  to  ensure  that  when  the  writing-point  of 
the  myograph  lever  has  been  once  adjusted  to  the  drum,  successive 
stimuli  will  cause  cor  tractions,  the  curves  of  which  all  rise  from  the 
same  point.  Close  the  key  in  the  primary,  set  the  drum  off  (fast  speed), 
open  the  short-circuiting  key,  and  as  soon  as  the  muscle  has  contracted 
once,  close  it  again.  Now  stop  the  drum,  mark  with  a  pencil  the 
position  of  the  feet  of  the  stand  carrying  the  myograph  plate,  take  the 
writing-point  off  the  drum,  and  surround  the  muscle  with  pounded  ice 
or  snow.  After  a  couple  of  minutes  brush  away  any  ice  which  could 
hinder  the  movement  of  the  muscle,  rapidly  replace  the  stand  in  exactly 
its  original  position,  with  the  writing-point  on  the  drum,  and  take 
another  tracing.  Again  take  off  the  writing-point,  and  remove  all 
unmelted  ice  or  snow.  With  a  fine-pointed  pipette  irrigate  the  muscle 
with  physiological  salt  sohition  at  30°  C,  and  quickly  take  another 
tracing.  Then  put  on  a  time-tracing  with  the  electrical  tuning-fork. 
Fig.  248,  p.  722,  shows  a  series  of  curves  obtained  in  this  way. 

7.  Influence  of  Load  on  the  Muscle- Curve.— Arrange  everything  as 
in  6.  Take  a  tracing  first  with  the  lever  alone,  then  with  a  weight  of 
10  grammes,  then  with  50,  100,  200,  and  500  grammes  (Fig.  247,  p.  722). 

8.  Influence  of  Fatigue  on  the  Muscle-Curve. — Arrange  as  in  7,  but 
leave  on  the  same  weight  (say  10  grammes)  all  the  time.  Place  the 
nerve  on  the  electrodes.  Leave  the  short-circuiting  key  open.  The 
nerve  will  be  stimulated  at  each  revolution  of  the  drum,  and  the  writing- 

{)oint  will  trace  a  series  of  curves,  which  become  lower,  and  especially 
onger,  as  the  preparation  is  fatigued.  Two  or  four  curves  can  be 
taken  at  the  same  time,  if  both  ends  of  one  or  of  two  brass  slips  .be 
arranged  so  as  to  make  contact  with  the  projecting  wire  at  an  interval 
of  a  semicircumference  or  quadrant  of  the  drum  (Fig.  278).  (For 
specimen  curve,  see  Fig.  279,  p.  787.) 

9.  Seat  of  Exhaustion  in  Fatigue  of  the  Muscle-Nerve  Preparation  for 
Indirect  Stimulation. — When  the  nerve  of  a  muscle-nerve  preparation 
has  been  stimulated  until  contraction  no  longer  occurs,  the  muscle  can, 
under  ordinary  conditions,  be  made  to  contract  by  direct  stimulation. 
The  seat  of  exhaustion  is,  therefore,  not  the  general  contractile  sub- 
stance of  the  muscular  fibres  themselves.  To  determine  whether  it  is 
the  nerve-fibres  or  some  structure  or  substance  intermediate  between 
them  and  the  ordinary  contractile  substance  of  the  muscle,  perform 
the  following  experiments : 

[a)  Pith  a  frog;  make  two  muscle-nerve  preparations;  arrange  them 
both  on  a  myograph  plate,  which  has  two  levers  connected  with  it. 
Attach  each  of  the  muscles  to  a  lever  in  the  usual  way,  and  lay  both 
nerves  side  by  side  on  the  same  pair  of  electrodes.  Cover  with  moist 
blotting-paper.  The  electrodes  are  connected  with  the  secondary  of  an 
induction  machine  arranged  for  tetanus.     With  a  camel's  hair  brush 


PRACTICAL  EXERCISES 


787 


moisten  one  of  the  nerves  between  the  electrodes  and  the  muscle  with  a 
mixture  ol  equal  parts  of  ether  and  alcohol,  diluted  with  twice  its  volume 
of  water,  to  abolish  the  conductivity.  Or  put  the  mixture  in  a  small 
bottle,  in  which  dips  a  piece  of  filter-paper.  The  projecting  end  of  the 
filter- pa  per  is  pointed,  and  the  nerve  is  laid  on  the  point.  As  soon  as 
it  is  possible  to  stimulate  the  nerves  without  obtaining  contraction  in 
this  muscle,  proceed  to  tetanize  both  nerves  till  the  contracting  muscle 
is  exhausted.  If  the  other  muscle  begins  to  twitch  during  the  stimu- 
lation, more  of  the  ether  mixture  must  be  painted  on  the  nerve.  As 
soon  as  the  stimulation  ceases  to  cause  contraction  in  the  non-etherized 
preparation,  wash  off  the  mixture  from  the  other  nerve  with  physio- 
logical salt  solution,  and  soon  contraction  may  be  seen  to  take  place  in 


rig.  279. — Fatigue  Curve  of  Skeletal  Muscle:  Gastrocnemius  of  Frog.  Indirect 
stimulation;  taken  with  arrangement  shown  in  Fig.  278  (p.  785).  Time-tracing, 
J  J5  of  a  second. 

the  muscle  of  this  preparation.  This  shows  that  the  nerve-trunk  is  still 
excitable.  Now,  both  nerves  have  been  equally  stimulated,  and  there- 
fore the  exhaustion  in  the  non-cthcrized  preparation  was  not  due  to 
fatigue  of  the  nerve-fibres,  but  of  something  between  them  and  the 
contractile  substance  of  the  muscle. 

10.  Influence  of  Veratrine  on  Muscular  Contraction.  —  Arrange  a 
drum  as  in  Fig.  27S.  Pith  a  frog  (brain  only),  expose  the  sciatic  nerve 
in  one  thigh,  and  isolate  it  for  \  inch  from  the  surrounding  tissues. 
Pass  under  it  a  strong  thread,  and  ligature  everything  except  the  nerve. 
Now  inject  into  the  dorsal  or  ventral  lymph-sac  a  few  drops  of  0*1  per 
cent,  solution  of  sulphate  of  veratrine.  In  a  few  minutes  make  two 
muscle-nerve  preparations  from  the  pxjsterior  limbs.  First  put  the 
preparation  from  the  unligatured  limb  on  the  myograph  plate.     Lay 


788  MUSCLE  AND  NERVE 

the  nerve  on  electrodes  connected  through  a  short-circuiting  key  with 
the  secondary  of  an  induction  machine  arranged  as  in  Fig.  278.  Put 
the  writing-point  on  the  drum  and  set  it  off  (fast  speed).  Open  the 
short-circuiting  key  till  the  nerve  has  been  once  stimulated,  then  close 
it  again.  The  curve  obtained  differs  from  a  normal  curve,  in  that 
the  period  of  descent  (relaxation)  is  exceedingly  prolonged.  Now 
connect  the  preparation  from  the  ligatured  limb  with  the  lever,  and 
take  a  tracing  of  a  single  contraction.  Put  on  a  time-tracing  with  the 
electrical  tuning-fork  (see  Figs.  257,  258,  p.  729). 

II.  Measurement  of  the  Latent  Period  of  Muscular  Contraction. — 
(i)  For  this  the  drum  must  travel  at  a  faster  speed  than  usual.  It 
is  most  convenient  to  use  a  drum  rotated  very  rapidly  by  a  cord 
attached  to  a  falling  weight  or  by  the  recoil  of  a  stretched  rubber  band 
or  spring.  The  arrangement  for  automatic  stimulation  described  in 
Experiment  6  (p.  786)  may  be  employed.  Or  an  electro-magnetic  signal 
may  be  connected  in  the  primary  circuit  of  the  induction  coil  so  that 
when  the  primary  is  closed  or  opened  the  writing-point  of  the  signal 
moves.  Arrange  the  writing-point  of  the  signal  on  the  drum  in  the 
same  vertical  line  as  the  writing-point  of  the  muscle  lever,  and  in  the 
same  line  place  the  writing-point  of  a  vibrating  electric  tuning-fork. 
The  coil  is  adjusted  for  single  opening  shocks  as  in  Experiment  5 
(p.  784).  Pith  a  frog,  and  make  a  muscle-nerve  preparation.  Arrange 
it  on  the  myograph  plate.  The  muscle,  or  the  nerve  very  near  the 
muscle,  is  to  be  excited  by  a  single  opening  shock  while  the  drum  is 
moving.  When  the  curve  has  been  traced,  the  latent  period  is  got  by 
drawing  a  vertical  line  through  the  point  at  which  the  curve  just  begins 
to  rise  from  the  abscissa  line,  and  another  through  the  signal  mark. 
The  number  erf  vibrations  of  the  tuning-fork  included  between  these 
two  verticals  gives  the  latent  period. 

Or  (2)  use  the  spring  myograph  (Fig.  244,  p.  720),  raising  it  on  blocks 
of  wood.  Smoke  the  glass  plate  over  a  paraffin  flame,  or  cover  it  with 
paper,  and  smoke  the  paper.  Connect  the  knock-over  key  of  the  myo- 
graph with  the  primary  circuit  of  an  induction  coil.  Arrange  a  muscle- 
nerve  preparation  on  the  myograph  plate.  Place  electrodes  below  the 
nerve  as  near  the  muscle  as  possible,  and  connect  by  a  short-circuiting 
key  with  the  secondary.  Bring  the  writing-point  in  contact  with  the 
smoked  surface  of  the  spring  myograph,  so  as  to  get  the  proper  pressure. 
See  that  the  writing-point  of  the  tuning-fork  is  in  the  right  position  for 
tracing  time.  Then  push  up  the  plate  so  as  to  compress  the  spring, 
till  the  rod  connected  with  the  frame  which  carries  the  plate  is  held  by 
the  catch. 

With  the  short-circuiting  key  closed,  press  the  release  and  allow  an 
abscissa  line  to  be  traced.  Again  shove  back  the  frame  till  it  is  caught. 
Push  home  the  rod  by  means  of  which  the  prongs  of  the  tuning-fork  are 
separated,  and  rotate  it  through  90°.  Close  the  knock-over  key,  open 
the  short-circuiting  key,  shoot  the  plate  again,  and  a  muscle-curve  and 
time-tracing  will  be  recorded.  Again  close  the  short-circuiting  key, 
withdraw  the  writing-point  of  the  tuning-fork,  push  back  the  plate, 
close  the  trigger  key,  then  open  the  short-circuiting  key,  and.  holding 
the  travelling  frame  with  the  hand,  allow  it  just  to  open  the  knock- 
over  and  stimulate  the  nerve.  The  writing-point  now  records  a  vertical 
line  (or,  rather,  an  arc  of  a  circle),  which  marks  on  the  tracing  the 
moment  of  stimulation.  The  latent  period  is  obtained  by  drawing  a 
parallel  line  (or  arc)  through  the  point  of  the  muscle-curve  where  it  just 
begins  to  diverge  from  the  abscissa  line.  The  value  of  the  portion  of  the 
time-tracing  between  these  two  lines  can  be  readily  determined,  and 
is  the  latent  period. 


PRACTICAL  EXERCISES  789 

12.  Summation  of  Stimuli. — Arrange  two  knock-over  keys  on  the 
spring  myograph  at  sucli  a  distance  from  each  other  that  the  plate 
travels  from  one  to  the  other  in  a  time  less  than  the  latent  period. 
Connect  each  key  with  the  primary  circuit  of  a  separate  induction  coil 
having  a  couple  of  Daniclls  in  it.  Join  two  of  the  binding-screws  of 
the  secondaries  together;  connect  the  other  two  through  a  short- 
circuiting  key  with  electrodes,  on  which  the  nerve  of  a  muscle-nerve 
preparation  is  arranged.  Push  up  the  secondaries  till  the  break  shocks 
obtained  on  opening  the  two  knock-over  keys  are  maximal.  Then 
shoot  the  plate  as  described  in  11,  first  with  one  trigger  key  closed,  and 
then  with  both.  The  curves  obtained  should  be  of  the  same  height  in 
the  two  cases,  as  a  second  maximal  stimulus  falling  within  the  latent 
period  is  ignored  by  the  nerve  or  muscle.  Repeat  the  experiment  with 
submaximal  stimuli — i.e.,  with  such  a  distance  of  the  coils  that  opening 
of  either  trigger  key  does  not  cause  as  strong  a  contraction  as  is  caused 
when  the  coils  are  closer.  The  curve  will  now  be  higher  when  the  two 
shocks  are  thrown  in  successively  than  when  the  nerve  is  only  once 
stimulated.  This  shows  that  (submaximal)  stimuli  can  be  summed  in 
the  nerve.     The  same  could  be  demonstrated  for  muscle  (p.  730). 

13.  Superposition  of  Contractions. — Smoke  a  drum  arranged  for  auto- 
matic stimulation  as  in  Fig.  278.  Adjust  the  brass  points  with  a 
distance  of,  say,  i  centimetre  between  them,  so  that  a  second  stimulus 
may  be  thrown  into  the  nerve  at  an  interval  greater  than  the  latent 
period  of  muscle.  Put  two  Daniells  in  the  primary  circuit.  Lay  the 
nerve  of  a  muscle-nerve  preparation  on  electrodes  connected  through  a 
short-circuiting  key  with  the  secondary.  Allow  the  drum  to  revolve 
(fast  speed) ;  open  the  short-circuiting  key  till  both  brass  points  have 
passed  the  projecting  wire,  then  close  it.  Now  bend  back  the  second 
brass  point,  and  take  a  tracing  in  which  the  first  curve  is  allowed  to 
complete  itself.  This  will  not  rise  as  high  as  the  second  curve  obtained 
when  the  two  stimuli  were  thrown  in.  Repeat  the  experiment  with 
varying  intervals  between  the  brass  points — that  is,  between  the  two 
successive  stimuli.  Put  on  a  time-tracing  with  the  electrical  tuning- 
fork.     (For  specimen  curve,  see  Fig.  259,  p.  730.) 

14.  Composition  of  Tetanus. — (a)  Adjust  a  muscle-nerve  preparation 
on  a  myograph  plate,  the  nerve  being  laid  on  electrodes  connected 
through  a  short-circuiting  key  with  the  .secondary  of  an  induction 
machine,  the  primary  circuit  of  which  contains  a  Daniell  cell  and  is 
arranged  for  an  interrupted  current  (Fig.  93,  p.  198).  The  lever  should 
be  shorter  than  that  used  for  the  previous  experiments,  or  the  thread 
should  be  tied  in  a  hole  farther  from  the  axis  of  rotation,  so  as  to  give 
less  magnification  of  the  contraction.  Set  the  Neef's  hammer  going, 
let  the  drum  revolve  (slow  speed),  and  open  the  key  in  the  secondary. 
The  writing-point  at  once  rises,  and  traces  a  horizontal  or  perhaps 
slightly-ascending  line.  Close  the  short-circuiting  key,  and  the  lever 
sinks  down  again  to  the  abscissa  line.  If  it  does  not  quite  return,  it 
should  be  loaded  with  a  small  weight.  This  is  an  example  of  complete 
tetanus. 

(6)  Connect  the  spring  shown  in  Fig.  280  with  one  of  the  upper 
terminals  of  the  primary  coil,  and  the  mercury  cup  with  the  other. 
Fasten  the  end  of  the  spring  in  one  of  the  notches  in  the  upright  piece 
of  wood  by  means  of  a  wedge,  so  that  its  whole  length  can  be  made  to 
vibrate.  Let  the  drum  off,  set  the  spring  vibrating  by  depressing  it 
with  the  finger,  then  open  the  key  in  the  secondar3^  The  muscle  is 
thrown  into  incomplete  tetanus,  and  the  writing-point  traces  a  wavy 
curve  at  a  higher  level  than  the  abscissa  line.  Close  the  short-circuiting 
key,  and  the  lever  falls  to  the  horizontal.     Repeat  the  experiment  with 


790 


MUSCLE  AND  NERVE 


Fig.  280. — Arrangement  for  Tetanus.  A,  upright  with 
notches,  in  which  the  spring  S  is  fastened  (shown  in 
section);  C,  horizontal  board  to  which  A  is  attached, 
and  in  a  groove  in  which  the  mercury-cup  E  slides. 
The  primary  coil  P  is  connected  with  E,  and  through 
a  simple  key,  K,  with  the  battery  B,  the  other  pole 
of  which  is  connected  with  the  end  of  the  spring. 
The  wires  from  the  secondary  coil,  P',  go  to  a  short- 
circuiting  key,  K',  from  which  the  wires  F  go  off  to 
the  electrodes. 


the  spring  fastened,  so  that  only  f .  ^,  J,  J  of  its  length  is  free  to  vibrate. 
The  rate  of  interruption  of  the  primary  circuit  increases  in  proportion 

to  the  shortening  of 

the  spring,  and  the 
tetanus  becomes  more 
and  more  complete, 
till  ultimately  the 
writing -point  marks 
an  unbroken  straight 
line.  Put  on  a  time- 
tracing  by  means  of 
an  electro  -  magnetic 
marker  connected 
with  a  metronome 
beating  seconds  or 
half-seconds  (Fig.  88, 
p.  193).  (For  speci- 
men curves,  see  Fig. 
260,  p.  730.) 

15.  Contraction  of 
Smooth  Muscles — 
(i)  Spontaneous 
Rhythmical  Contrac- 
tions. —  Immerse  in 
oxygenated  Ringer's 
solution  a  ring  of 
oesophagus  obtained 
immediately  after  death  from  a  cat,  or,  still  better,  from  a  chicken.  Or 
a  segment  of  rabbit's  intestine  may  be  employed  as  described  on  p.  446. 
Use  the  arrangement 
described  on  p.  446.  In 
the  case  of  the  cat's  oeso- 
phagus the  ring  should 
be  taken  from  the  lower 
half  of  the  oesophagus, 
since  the  upper  portion 
contains  purely  striated 
muscle.  Obtain  tracings 
of  the  rhythmical  con- 
tractions on  a  slowly- 
moving  drum  (Fig.  281). 
(2)  Fix  one  end  of 
a  piece  of  cat's  oeso- 
phagus, 2  to  5  centi- 
metres long,  to  a  muscle- 
clamp  in  a  moist 
chamber,  and  the  other 
end  to  a  lever  writing 
on  a  drum.  Connect 
thin  copper  wires  from 
the  secondary  coil  of  an 
inductorium  with  the 
two  ends  of  the  piece 
of    oesophagus.       Take 

tracings  to  show  (a)  the  curve  of  a  single  contraction  caused  by  a  single 
make  or  break  shock,  with  estimation  of  the  latent  period,  as  in  Experi- 
ment II,  p.  788;  (6)  summation,  as  in  Experiment  12,  p.  789;  (c)  genesis 


Fig.  281 


-Rhythmical  Contractions  of  Olsophagus  of 
Chicken  (BotazzI). 


PRACTICAL  EXERCISES 


791 


of  tetanus,  as  in  Experiment  14,  p.  789;  (d)  the  relations  between 
strength  of  stinuihis  and  amount  of  contraction.  For  this  last  experi- 
ment the  drum  should  be  stationary  while  the  contraction  is  being 
recorded,  and  sliculd  be  allowed  to  move  a  little  between  successive 
contractions.  Begin  with  the  secondary  at  such  a  distance  from  the 
primary  that  a  contraction  is  just  caused  by  a  break  shock.  Then 
gradually  increase  the  strength  of  the  stimulus  (always  using  the  break) 
till  maximum  contraction  is  obtained.  The  gradual  increase  in  the 
response  is  very  clearly  seen  with  the  oesophageal  preparation  (Waller). 

For  further  experiments  on  the  contraction  of  smooth  muscle,  see 
pp.  66  and  447. 

16.  Velocity  of  the  Nerve-Impulse. — Use  the  spring  myograph 
(Fig.  244,  p.  720)  or  a  very  rapitlly  rotating  drum.  Make  a  muscle- 
nerve  preparation  from  a  large  frog  (preferably  a  bull-frog),  so  that  the 
sciatic  nerve  may  be  as  long  as  possible.  Connect  the  knock-over  key 
with  the  primary  circuit  of  an  induction  machine,  which  should  contain 


Fig.  282. — .\rrangement  for  Measuring  the  Velocity  of  the  Nerve-Impulse.  A.  travel- 
ling plate  of  spring  myograph;  M,  muscle  lying  on  a  myograph  plate;  N,  nerve 
lying  on  two  pairs  of  electrodes,  E  and  E';  C,  Pohl's  commutator  without  cross- 
wires;  K,  knock-over  key  of  spring  myograph  (only  the  binding-screws  shown); 
K',  simple  key  in  primary  circuit;  B,  battery;  P,  primary  coil;  S,  secondary  coil. 

a  single  Daniell  cell.  Arrange  two  pairs  of  fine  electrodes  under  the 
nerve  on  the  myograph  plate,  one  near  the  muscle,  the  other  at  the 
central  end.  Connect  the  electrodes  with  a  Pohl's  commutator  (with- 
out cross-wires),  the  side-cups  of  which  are  joined  to  the  terminals  of 
the  secondary  coil,  as  shown  in  Fig.  282.  By  tilting  the  bridge  of  the 
commutator  the  nerve  may  be  stimulated  at  either  point.  Great  care 
must  be  taken  to  keep  the  nerve  in  a  moist  atmosphere  by  means  of  wet 
blotting-paper  or  a  moist  chamber;  but  at  the  same  time  it  must  not 
lie  in  a  pool  of  salt  solution,  as  twigs  of  the  stimulating  current  would 
in  this  case  spread  down  the  nerve;  and  we  could  never  be  sure  that 
the  apparent  was  always  the  real  point  of  stimulation.  The  writing- 
points  of  the  lever  and  tuning-fork  having  been  adjusted  to  the  smoked 
plate,  as  in  11  (p.  788),  the  bridge  of  the  Pohl's  commutator  is  arranged 
for  stimulation  ot  the  distal  point  of  the  nerve,  the  plate  is  shot  with 
the  short-circuiting  key  in  the  secondary  closed,  and  an  abscissa  line 
and  time-curve  traced.  Then  the  writing-point  of  the  fork  is  removed 
and  the  plate  again  shot  with  the  key  in  the  secondary  open,  and  a 


792  MUSCLE  AND  NERVE 

muscle-curve  is  obtained.  The  commutator  is  now  arranged  for  stimu- 
lation of  the  central  end  of  the  nerve,  and  another  mu3cle-curve  taken. 
Vertical  lines  are  drawn  through  the  points  where  the  two  curves  just 
begin  to  separate  out  from  the  abscissa  lino.  The  interval  between 
these  lines  corresponds  to  the  time  taken  by  the  nerve-impulse  to  travel 
along  the  nerve  from  the  central  to  the  distal  pair  of  electrodes.  Its 
value  in  time  is  given  by  the  tracing  of  the  tuning-fork.  The  length  of 
the  nerve  between  the  two  pairs  of  electrodes  is  now  carefully  measured 
with  a  scale  divided  in  millimetres,  and  the  velocity  calculated  (p.  767). 

17.  Chemistry  of  Muscle. — Mince  up  some  muscle  from  the  hind-legs 
of  a  dog  or  rabbit  (used  in  some  of  the  other  experiments),  of  which 
the  bloodvessels  have  been  washed  out  by  injecting  0*9  per  cent,  salt 
solution  through  a  cannula  tied  into  the  abdominal  aorta  until  the 
washings  are  no  longer  tinged  with  blood.  To  some  of  the  minced 
muscle  add  twenty  times  its  bulk  of  distilled  water,  to  another  portion 
ten  times  its  bulk  of  a  5  per  cent,  solution  of  inagnesium  sulphate. 
Let  stand,  with  frequent  stirring,  for  twenty-four  hours.  Then  strain 
through  several  folds  of  linen,  press  out  the  residue,  and  filter  through 
paper,  (i)  With  the  filtrate  of  the  watery  extract  make  the  following 
observations : 

{a)  Reaction. — To  litmus-paper  acid. 

[b)  Determine  the  temperatures  at  which  coagulation  of  the  various 
proteins  in  the  extract  takes  place,  according  to  the  method  described 
on  p.  9.*  Put  some  of  the  watery  extract  in  the  test-tube,  and  heat 
the  bath,  stirring  the  water  in  the  beakers  occasionally  with  a  feather. 
Note  at  what  temperature  a  coagulum  first  forms.  It  will  be  about 
47°  C.  Filter  this  off,  and  again  heat;  another  coagulum  will  form  at 
56°  to  58°.  Filter,  and  heat  the  filtrate;  a  third  slight  coagulum  may 
be  formed  at  60°  to  65°  C,  but  this  repi'esents  merely  a  residue  of  the 
myosinogen  which  was  left  in  solution  at  the  previous  heating.  A 
fourth  precipitate  (of  serum-albumin)  will  come  down  at  70°  to  73°. 
Saturate  some  of  the  watery  extract  with  magnesium  sulphate ;  a  large 
precipitate  will  be  formed,  showing  the  presence  of  a  considerable 
amount  of  globulin.  Filter  off  the  precipitate  and  heat  the  filtrate; 
coagulation  will  again  occur  at  very  much  the  same  temperatures  as 
before,  although  the  total  amount  of  precipitate  will  be  less.  Note  in 
particular  that  there  is  still  some  precipitate  at  47°  to  50°.  Paramyo- 
sinogen possesses  some  of  the  characters  of  both  globulins  and  albumins, 
for  it  is  partially  but  not  entirely  precipitated  by  saturation  with 
magnesium  sulphate,  and  is  not  precipitated  by  sodium  chloride. 

(2)  (a)  Test  the  reaction  of  the  magnesium  sulphate  extract.  It 
will  usually  be  faintly  acid  to  litmus. 

[b]  Heat  some  of  it.  Precipitates  will  be  obtained  at  the  same  tem- 
peratures as  in  (i)  ib),  but  those  at  47"  to  50°  and  56°  to  58°  will  be 
more  abundant.  Of  the  two,  that  at  47°  to  50°  will  usually  be  the 
larger  when  time  is  given  for  it  to  come  down  and  the  heating  is  gradual. 

(c)  Dilute  some  of  the  magnesium  sulphate  extract  with  three  times, 
another  portion  with  four  times,  and  another  with  five  times,  its  volume 
of  water  in  a  test-tube,  and  put  in  a  bath  at  40°  C.     Coagulation  or 

*  It  should  be  remembered  that  the  temperature  of  heat-coagulation  of 
any  substance  is  by  no  means  an  absolute  constant.  It  depends  on  the 
reaction,  the  proportion  and  kind  of  neutral  salts  present,  perhaps  on  the 
strength  of  the  protein  solution  and  the  manner  of  heating.  A  solution  ol 
egg-albumin,  e.g.,  can  be  coagulated  at  a  temperature  much  below  70°  when 
it  is  heated  for  a  week.  Small  differences  in  the  temperature  of  heat-coagula- 
tion, unless  supported  by  well-marked  chemical  reactions,  are  not  enough 
to  characterize  protein  substances  as  chemical  individuals. 


PRACTICAL  EXERCISES  793 

precipitation  will  occur  in  one  or  all  of  these  test-tubes.  To  another 
test-tube  of  the  extract  diluted  in  the  proportion  which  has  given  the 
best  '  muscle-clot  '  add  a  few  drops  of  a  dilute  solution  of  potassium 
oxalate,  and  place  in  a  bath  at  40°.  Coagulation  occurs  as  before. 
Filter  off  the  clot  from  all  the  test-tubes.  The  filtrate  is  the  '  muscle- 
serum,'  and  yields  a  precipitate  of  serum-albumin  at  70°  to  73°  C. 

(3)  Myosinogoi.  like  other  globulins',  is  insoluble  in  distilled  water, 
but  soluble  in  weak  saline  solutions.  Saturation  with  neutral  salts  like 
sodium  chloride  and  magnesium  sulphate  precipitates  mycsinogen,  but 
not  albumin,  from  its  solutions;  saturation  with  ammonium  sulphate 
precipitates  both.  Verify  the  following  reactions  of  myosinogen,  using 
the  original  magnesium  sulphate  extract  of  the  muscle : 

(a)  Dropped  into  water,  it  is  precipitated  in  flakes,  which  can  be 
redissolved  by  a  weak  solution  of  a  neutral  salt  (say  5  per  cent,  mag- 
nesium sulphate). 

(6)  When  a  solution  of  myosinogen  is  dialyzed,  it  is  after  a  time  pre- 
cipitated on  the  inside  of  the  dialyzer  as  the  salts  pass  out. 

(c)  If  a  piece  of  rock-salt  is  suspended  in  a  solution,  the  myosin 
gradually  gathers  upon  it,  diffusion  of  the  salt  out  through  the  precipi- 
tated myosin  always  keeping  a  saturated  layer  aroimd  it. 

{(i)  Saturate  a  solution  containing  myosinogen  with  crystals  of 
magnesium  sulphate,  stirring  or  shaking  at  frequent  intervals.  The 
myosinogen  is  precipitated. 

(e)  Without  adding  any  salt,  simply  shake  a  myosinogen  solution 
vigorously;  a  certain  amount  of  the  myosinogen  will  be  precipitated 
and  the  solution  will  become  turbid.  This  reaction  can  also  be  ob- 
tained with  solutions  of  other  proteins,  such  as  albumins  (Ramsden). 

Extracts  qualitatively  siniilar  to  those  obtained  from  the  muscles 
of  a  freshly-killed  animal  can  be  got  from  muscles  that  have  entered 
into  rigor,  but  the  quantity  of  the  various  proteins  going  into  solution 
is  less. 

18.  Reaction  of  Muscle  in  Rest,  Activity,  and  Rigor  Mortis. — (a)  Take 
a  frog's  muscle,  cut  it  across,  and  press  a  piece  of  red  litmus-paper  on 
the  cut  end;  it  is  turned  blue.     Yellow  turmeric  paper  is  not  afiected. 

(b)  Immerse  another  muscle  in  physiological  salt  solution  (0*75  per 
cent,  for  frog's  tissues)  at  40°  to  42°  C.  It  becomes  rigid.  The  reaction 
becomes  acid  to  litmus-paper,  and  also  turns  brown  turmeric  paper 
yellow. 

(c)  Plunge  another  muscle  into  boiling  physiological  salt  solution. 
It  becomes  harder  than  in  (b). 

(d)  Stimulate  another  muscle  with  an  interrupted  current  from  an 
induction  machine  (Fig.  93,  p.  198),  till  it  no  longer  contracts.  The 
reaction  is  now  acid  to  litmus-paper.  Brown  turmeric  paper  may  also 
be  turned  yellow. 

(e)  To  demonstrate  the  formation  of  lactic  acid  in  muscle  in  heat 
rigor  or  fatigue,  perform  the  following  experiment:  Pith  a  frog,  and 
afterwards  leave  it  for  half  an  hour  at  rest,  so  that  the  lactic  acid  pro- 
duced in  the  movements  connected  with  the  pithing  operation  may 
disappear  from  the  muscles.  See  that  the  circulation  in  the  hind-limbs 
is  not  interfered  with  by  pressure  or  flexion.  Then  remove  both  hind- 
limbs.  Carefully,  but  rapidly,  remove  the  muscles  of  one  from  the 
bones  with  as  little  manipulation  as  possible.  Immediately  place  them 
in  a  small  mortar  cooled  in  ice,  and  containing  some  sand  and  20  or 
30  c.c.  of  ice-cold  95  per  cent,  alcohol,  and  quickly  grind  them  up. 
Produce  heat  rigor  (p.  751)  of  the  muscles  of  the  other  hind-limb,  or 
fatigue  them  with  induction-shocks,  and  then  grind  them  up  under 
alcohol   in   the   same   way.     Filter  the   alcoholic  extracts,   and   then 


794  MUSCLE  AND  NERVE 

evaporate  them  to  dryness  on  the  water-bath.  Rub  up  the  residues 
with  a  few  c.c.  of  hot  water.  Add  to  each  aqueous  extract  a  sinall 
quantity  (say  a  decigramine)  of  finely  powdered  charcoal.  Then  heat 
each  extract  to  boiling  in  a  test-tube,  and  filter.  Evaporate  the 
filtrates  to  dryness,  and  apply 

Hopkins's  Reaction  for  Lactic  Acid. — The  reagents  required  are  (i)  a 
very  dilute  alcoholic  solution  of  thiophene  {C4H4S)  (10  to  20  drops  in 
100  c.c);  (2)  a  saturated  solution  of  copper  sulphate;  and  (3)  ordinary 
strong  sulphuric  acid. 

Have  ready  a  glass  beaker  containing  water  briskly  boiling.  Place 
about  5  c.c.  of  strong  sulphuric  acid  in  a  test-tube,  with  i  drop  of  tht. 
copper  sulphate  solution.*  Add  to  the  mixture  a  few  drops  of  the 
solution  to  be  tested,  and  shake  well.f 

(In  the  case  of  the  muscle  extracts  the  dry  residues  arc  dissolved  in 
the  5  c.c.  of  strong  sulphuric  acid,  the  acid  transferred  to  test-tubes, 
and  the  test  proceeded  with  by  the  addition  of  the  copper  sulphate 
solution,  etc.) 

Now  place  the  test-tube  in  the  boiling  water  for  one  to  two  minutes. 
Then  cool  it  well  under  the  cold-water  tap,  and  add  2  or  3  drops  of 
the  thiophene  solution  from  a  pipette.  Replace  the  tube  in  the  boiling 
water,  and  immediately  observe  the  colour.  If  lactic  acid  is  present, 
the  liquid  rapidly  takes  on  a  bright  cherry-red  colour,  which  is  only 
permanent  if  the  test-tube  be  cooled  immediately  after  its  appearance. 
The  tube  should  always  be  cooled  as  described,  before  addition  of  the 
thiophene,  as  the  gradual  appearance  of  the  colour  on  re- warming 
makes  the  test  more  delicate. 

(The  extract  of  the  resting  limb  generally  gives  a  negative,  that  of 
the  other  a  strongly  positive,  reaction.) 

*  The  copper  sulphate  is  added  to  hasten  the  oxidation  that  follows. 

f  For  practice  use  a  i  per  cent,  alcoholic  solution  of  lactic  acid.  The  test 
cannot  be  applied  directly  to  material  which  chars  with  the  strong  sulphuric 
acid  used.  In  this  case  preliminary  extraction  of  the  lactic  acid  is  necessary. 
Alcohol  should  be  used  as  the  solvent,  or  if  ether  is  employed  it  must  first  be 
well  washed  to  remove  aldehyde-yielding  products,  since  the  colour-change  is 
due  to  an  aldehyde  reaction  with  thiophene. 


CHAPTER  XV 
ELECTRO-PHYSIOLOGY 

A  LITTLE  more  than  a  hundred  years  ago  the  foundation  both  of  electro- 
physiology  and  of  the  vast  science  of  voltaic  electricity  was  laid  by  a 
chance  observation  of  a  professor  of  anatomy  in  an  Italian  garden.  It 
.«;>  indeed  true  that  long  before  this  electrical  fishes  were  not  only 
popularly  known,  but  the  shock  of  the  torpedo  had  been  to  a  certain 
extent  scientifically  studied.  But  it  was  with  the  discovery  of  Galvani 
of  Bologna  that  the  epoch  of  fruitful  work  in  electro-physiology  began. 
Engaged  in  experiments  on  the  effect  of  static  and  atmospheric  elec- 
tricity in  stimulating  animal  tissues,  he  happened  one  day  to  notice 
that  some  frogs'  legs,  suspended  by  copper  hooks  on  an  iron  railing, 
twitched  whenever  the  wind  brought  them  into  contact  with  one  of 
the  bars  (p.  814).  He  concluded  that  electrical  charges  were  developed 
in  the  animal  tissues  themselves,  and  discharged  when  the  circuit  was 
completed.  Volta,  professor  of  physics  at  Pa  via,  fixing  his  attention  on 
the  fact  that  in  Galvani's  experiment  the  metallic  part  of  the  circuit 
was  composed  of  two  metals,  maintained  that  the  contact  of  these  was 
the  real  origin  of  the  current,  and  that  the  tissues  served  merely  as 
moist  conductors  to  com^plete  the  circuit ;  and  after  a  controversy  lasting 
for  more  than  a  decade,  he  finally  clinched  his  argument  by  constructing 
the  voltaic  pile,  a  series  of  copper  and  zinc  discs,  every  two  pairs  of 
which  were  separated  by  a  disc  of  wet  cloth,  or  paper  moistened  with  salt 
solution.  The  pile  yielded  a  continuous  current  of  electricity.  '  So,' 
said  Volta,  '  it  is  clear  that  the  tissue  in  Galvani's  experiment  only  acts 
the  part  of  the  cloth.'  Galvani,  however,  had  shown  in  the  meantime 
that  contraction  without  meials  could  be  obtained  by  dropping  the  nerve 
of  a  preparation  on  to  the  muscle  (p.  814) ;  and  it  soon  began  to  be  recog- 
nized that  both  Galvani  and  Volta  were  in  part  right,  that  the  tissues 
produce  electricity,  and  that  the  contact  of  different  metals  does  so 
too.  Although  it  is  curious  to  note  how  completely  the  growth  of 
that  science  of  which  Volta's  discovery  was  the  germ  has  overshadowed 
the  parent  tree  planted  by  the  hand  of  Galvani,  yet  animal  electricity 
has  been  deeply  studied  by  a  large  number  of  observers,  and  many 
interesting  and  important  facts  have  been  brought  to  light. 

Since  it  is  in  muscle  and  nerve  that  the  phenomena  of  electro- 
physiology  are  seen  in  their  simplest  expression,  and  have  been 
chiefly  studied,  we  shall  develop  the  fundamental  laws  with  reference 
to  muscle  and  nerve  alone,  and  afterwards  apply  them  to  other 
excitable  tissues. 

I.  All  points  of  an  uninjured  resting  muscle  or  nerve  are  approxi- 
mately at  the  same  potential  {or  iso- electric).     In  other  words,  if  any 

795 


796 


ELECTRO-PH  YSIOLOG  Y 


two  points  are  connected  with  a  galvanometer  by  means  of  un- 
polarizable  electrodes,  little  or  no  current  is  indicated.  (Although 
it  is  scarcely  possible  to  isolate  a  muscle  without  its  showing  some 
current,  the  more  carefully  the  isolation  is  performed,  the  feebler 
is  the  current;  and  between  two  points  of  the  inactive,  uninjured 
ventricle  of  the  frog's  heart  no  electrical  difference  has  been  found. 
Frogs'  nerves  kept  ten  to  twenty  hours  after  excision  in  physiological 
salt  solution  to  which  a  little  calcium  salt  and  frog's  blood  have 
been  added,  are  absolutely  iso-electric.) 

2.  Any  uninjured  point  of  a  resting  muscle  or  nerve  is  at  a  different 
potential  from  any  injured  point.  The  difference  of  potential  is  such 
that  a  current  will  pass  through  the  galvanometer  from  uninjured  to 
injured  point  and  through  the  tissue  from  injured  to  uninjured  point 
(current  of  rest,  or  demarcation  current,  or  injury  response)  (Fig.  283). 

3.  Any  unexcited  point  of  a  muscle  or  nerve  is  at  a  different  potential 
from  any  excited  point,  and  any  less  excited  point  is  at  a  different 


Fig.  283. — A,  uninjured,  B,  injured, 
portion  of  nerve;  G,  galvanometer. 
The  large  arrows  show  direction  of 
demarcation  current  or  current  of 
rest,  the  small  arrows  direction  of 
negative  variation  or  action  current. 


Fig.  284.  —  Diagram  of  Currents  of 
Rest  in  a  Regular  Muscle,  or  Muscle 
Cylinder.  E,  equator.  The  dotted 
lines  join  points  at  the  same  po- 
tential, between  which  there  is  no 
current. 


potential  from  any  more  excited  point.  The  difference  of  potential 
is  such  that  a  current  will  pass  through  the  galvanometer  to  the 
excited  from  the  unexcited  or  less  excited  point  (action  current, 
01  negative  variation,  or  excitatory  electrical  response). 

It  has  been  customary  in  physiological  writings  to  speak  of  the 
electrical  change  in  injured  or  active  tissue  as  a  negative  one,  because 
when  the  tissue  is  led  off  to  a  galvanometer  the  current  passes  from 
the  galvanometer  to  the  injured  or  excited  portion  of  the  tissue. 
It  may  be  called  with  greater  precision  ' galvanometrically  negative.' 
It  is  in  this  sense  that  we  shall  employ  the  term. 

The  best  object  for  experiments  on  the  demarcation  current  is  a 
straight-fibred  muscle  like  the  frog's  sartorius.  If  this  muscle  be  taken, 
and  the  ends  cut  off  perpendicularly  to  the  surface,  a  muscle-prism  or 
muscle-cylinder  is  obtained  (Fig.  284).  The  strongest  current  is  got 
when  one  electrode  is  placed  on  the  middle  of  either  cross-section,  and 
the  other  on  the  '  equator  ' — that  is,  on  a  line  passing  round  the  longi- 
tudinal surface  midway  between  the  ends.  The  direction  of  this 
current  is  from  the  cross-section  towards  the  equator  in  the  muscle. 
If  the  electrodes  are  placed  on  symmetrical  points  on  each  side  of  the 
equator,  there  is  no  current. 


NEGATIVE  VARIATION  797 

Current  of  Action,  or  Negative  Variation. — When  a  muscle  or 
nerve  is  excited,  an  electrical  change  sweeps  over  it  in  the  form  of 
a  wave.  Suppose  two  points,  A  and  B  (Fig.  285),  on  the  longi- 
tudinal surface  of  a  nmscle  to  be  connected  with  a  capillary  electro- 
meter (p.  702),  the  movements  of  the  mercury  being  photographed 
on  a  travelling  surface — for  example,  a  pendulum  carrying  a  sensitive 
plate.  Let  the  muscle  be  excited  at  the  end,  so  that  the  wave  of 
excitation  will  be  propagated  in  the  direction  of  the  arrow.  The 
wave  will  reach  A  first,  and  while  it  has  not  yet  rearhed  B,  A  will 


Fig.  285. — Diagram  to  illustrate  Propagation  of  the  Electrical  Change  along  an 
Active  Muscle  or  Nerve.  Suppose  AB  to  be  a  horizontal  bar  representing  the 
muscla  or  nerve.  Let  C  be  a  curved  piece  of  wood  representing  the  curve  of  the 
electrical  change  at  any  point.  Let  \V,  W  be  two  glass  cylinders  connected  by 
a  flexible  tube,  the  whole  being  filled  with  water.  Suppose  the  rims  of  the 
cylinders  originally  to  touch  AB  at  the  points  A  and  B,  and  let  them  be  movable 
only  in  the  vertical  direction.  The  level  of  the  water  being  the  same  in  both, 
there  is  no  tendency  for  it  to  flow  from  one  to  the  other.  This  represents  the  resting 
state  of  the  tissue  when  A  and  B  are  symmetrical  points.  Now  let£  be  moved 
along  the  bSr  at  a  uniform  rate.  The  cylinder  VV,  being  free  to  move  down,  but 
not  horizontally,  will  be  displaced  by  C,  and,  if  it  is  kept  always  in  contact  with 
its  curved  margin,  will,  after  describing  the  curve  of  the  electrical  variation, 
come  again  to  rest  in  its  old  position  at  A.  B  will  do  the  same  when  C  reaches 
it.  But  since  C  reaches  A  before  B,  the  level  of  the  water  in  B  will  at  first  be 
higher  than  that  in  A,  and  water  will  flow  from  B  to  A  as  the  current  flows 
through  the  galvanometer.  This  will  correspond  to  the  time  during  which  the 
point  of  the  tissue  represented  by  A  would  be  galvanometrically  negative  to  a 
point  represented  by  B.  Later  on,  when  C  has  reached  the  position  shown  by 
the  dotted  lines,  the  level  of  the  water  in  A  will  be  higher  than  that  in  B,  and  a 
flow  will  take  place  in  the  opposite  direction  to  the  first  flow.  This  corresponds 
to  a  second  phase  of  the  electrical  variation. 

become  negative  to  B.  If  there  is  a  resting  difference  of  potential 
between  A  and  B,  this  will  be  altered,  the  new  and  transitory  differ- 
ence adding  itself  algebraically  to  the  old.  When  the  wave  reaches 
B,  it  may  already  have  passed  over  A  altogether,  and  B  now  be- 
coming negative  to  A,  there  will  be  a  movement  of  the  meniscus 
of  the  electrometer  in  the  opposite  direction.     This  is  called  the 


798  ELECTRO-h-HYSIOLOGY 

diphasic  current  of  action.  If  the  wave  has  not  passed  over  A  before 
it  reaches  B,  as  would  in  general  be  the  case  in  an  actual  experiment, 
there  will  be  first  a  period  during  which  A  is  relatively  negative  to 
B  (first  phase) ;  this  will  end  as  soon  as  B  has  become  iso-electric 
with  A,  and  will  be  succeeded  by  a  period  during  which  B  is  rela- 
tively negative  to  A  (second  phase).  Since  the  wave  takes  time  to 
reach  its  maximum,  it  is  evident  that  a  well-marked  first  phase  will 
be  favoured  when  the  interval  between  its  arrival  at  A  and  at  B  is 
long,  for  in  this  case  A  will  have  a  chance  of  becoming  strongly 
negative  while  B  is  still  normal.  Similarly,  if  A  has  again  become 
normal,  or  nearly  normal,  before  the  maximum  negative  change  has 
passed  over  B,  a  strong  second  phase  will  be  favoured.  The  heart- 
muscle,  accordingly,  where  the  wave  of  contraction,  and  its  accom- 
panjdng  electrical  change,  move  with  comparative  slowness,  is 
better  suited  for  showing  a  well-marked  diphasic  variation  than 
skeletal  muscle,  and  still  better  suited  than  nerve.     In  the  gastroc- 


Fig.  286. — Photographic  Electrometer  Curves  from  Sartorius  Muscle  (Sanderson). 
The  darkly-shaded  curve  represents  the  diphasic  variation  of  the  uninjured 
muscle;  the  lightly-shaded  curve  the  monophasic  variation  of  the  muscle  after 
injury  of  one  end.  The  toothed  curve  at  the  top  is  the  time-tracing  registered  by 
photographing  the  prong  of  a  tuning-fork  vibrating  five  hundred  times  a  second. 

nemius  muscle  of  the  frog,  when  excited  through  its  nerve,  the  elec- 
trical response  begins  about  y^Vrr  second,  and  the  change  of  form  of 
the  muscle  about  xtroo  second,  after  the  stimulation.  It  is  believed 
that  in  a  muscle  directly  excited  the  electrical  change  begins  in  less 
than  YoVry  second,  and  the  mechanical  change  in  y^nr  second  (Burdon 
Sanderson,  Figs.  286-291). 

When  one  electrode  is  placed  on  an  injured  part,  the  wave  of  action 
and  of  electrical  change  diminishes  as  it  reaches  the  injured  tissue; 
and  if  the  tissue  is  killed  at  this  part,  it  diminishes  to  zero;  so  that 
here  the  second  phase  may  be  greatly  weakened  or  may  disappear 
altogether,  and  we  then  have  what  is  called  a  monophasic  variation. 

In  this  case  the  current  of  action  can  be  demonstrated,  even  for  a 
single  excitation,  but  still  better  for  a  tetanus,  with  an  ordinary  galvan- 
ometer, which  in  general  is  not  quick  enough  to  analyze  a  diphasic 
variation  with  equal  phases,  and  gives,  therefore,  only  their  algebraic 
sum — that  is,  zero.  When  the  muscle  or  nerve  is  tetanized,  the  action 
current  appears,  while  stimulation  is  kept  up,  as  a  permanent  deflection 
representing  the  '  sum  '  of  the  separate  effects.  It  is  in  the  opposite 
direction  to  the  current  oi  rest,  since  the  injured  tissue,  being  less 


NEGATIVE    VARIATION 


799 


affected  by  the  excitation,  and  therefore  undergoing  a  smaller  negative 
change  than  the  uninjured,  becomes  relatively  to  the  latter  less  nega- 
tive. Appearing  as  a  diminution  or  reversal  of  the  current  of  rest,  it  was 
called  the  negative  variation.  The  term  negative  is  not  used  here  in 
its  electrical,  but  in  its  algebraic,  sense,  and  merely  as  indicating  the 
direction  of  the  current  with  reference  to  that  of  the  demarcation 
current.  It  is  in  this  sense  that  '  negative  variation  '  and  the  converse 
term,  '  positive  variation,'  are  used  (pp.  8io,  81 1  )in  speaking  of  the 
electrical  changes  produced  in  glands  and  in  the  retina  by  stimulation. 


jvyryrun 


Fif 


A. 
,  287. 


-'  Spike  '  (Diphasic  Variation)  of  Uninjured 
Gastrocnemius    (Sanderson). 


A  photographed  on  slow,  B  on  fast -moving,  plate. 


Fig.  288. — Variation  of  In- 
jured Gastrocnemius  (San- 
derson). A  'spike'  fol- 
lowed by  a  '  hump.' 


Fig.  289.— Variation  of  Injured  Gas- 
trocnemius (Sanderson).  The  plate 
was  moving  ten  times  faster  than  ii. 
Fig.  288. 


Fig.  290. — Variation  of  Uninjured 
Muscle  excited  Eighty -Four  Times 
a  Second  (Sanderson). 


pjg  291.— Curve  of  an  Injured  Muscle  excited  Sixty  Times  a  Second  (Sanderson). 


goo  ELECTRO-PHYSIOLOGY 

When  the  current  of  rest  is  compensated  by  a  branch  of  an  external 
current  just  sufficient  to  balance  it  and  bring  the  galvanometer  image 
back  to  zero  (Fig.  226,  p.  701),  the  action  current  appears  alone  in  un- 
diminished strength.  This  shows  that  the  latter  ib  not  due  to  a  change 
of  electrical  resistance  during  excitation,  since  such  a  change  would 
equally  affect  current  of  rest  and  compensating  current,  and  they  would 
still  balance  each  other.  The  action  current  is  really  due  to  a  change 
of  potential,  which  can  be  measured  by  determining  what  electro- 
motive force  is  just  required  to  balance  it,  and  which  may  actually 
exceed  that  of  the  current  of  rest.  Thus,  Sanderson  and  Gotch  obtained 
an  average  of  o-o8  of  a  Daniell  cell  (the  electromotive  force  of  the 
Daniell  would  be  about  a  volt)  as  the  electromotive  force  of  the  action 
current  due  to  a  single  indirect  excitation  of  a  vigorous  frog's  gastroc- 
nemius, and  about  0*04  Daniell  as  that  of  the  current  of  rest.  The 
electromotive  force  of  the  current  of  rest  in  the  rabbit's  nerve  was 
found  by  du  Bois-Reymond  to  be  0*026;  Gotch  and  Horslcy  found  the 
average  for  the  cat  o^oi,  and  for  the  monkey  only  0-005. 

That  the  fusion  of  the  successive  variations  of  a  tetanized  muscle, 
as  seen  with  an  ordinary  galvanometer,  is  only  apparent  has  been 
shown  by  means  of  the  capillary  electrometer  or  the  string  galvanometer. 
Even  with  a  frequency  of  stimulation  far  beyond  what  is  necessary  for 
complete  tetanus,  each  stimulus  is  answered  by  a  movement  of  the 
meniscus  (Figs.  290,  291).  In  nerve,  also,  each  of  two  successive 
stimuli  causes  its  appropriate  electrical  change  when  they  are  separated 
by  an  interval  longer  than  a  certain  small  fraction  of  a  second.  The 
precise  interval  at  which  the  second  stimulus  ceases  to  be  effective 
depends  on  the  temperature  of  the  nerve,  being  markedly  increased  by 
cold  (Gotch  and  Burch) . 

The  rate  of  propagation  of  the  electrical  change  in  muscle  is  the 
same  as  that  of  the  mechanical  change,  and  in  nerve  the  same  as  that 
of  the  nervous  impulse.  The  velocity  of  propagation  of  the  diphasic 
variation  along  a  fresh  sartorius  at  14°  C.  was  in  one  experiment 
2'8  metres,  in  another  at  18°  C;  3-5  metres  (Sanderson).  (See  p.  733.) 
Lucas  has  pointed  out  that  in  strict  accuracy  what  is  observed  is  merely 
that  the  time  interval  separating  contraction  at  one  point  of  the  muscle 
from  contraction  at  another  is  equal  to  the  time  interval  separating 
the  electrical  changes  which  occur  at  the  same  points.  The  facts 
observed  do  not  formally  prove  that  either  the  contraction  or  the  elec- 
trical disturbance  is  propagated  at  all.  So  far  as  they  go,  some  other 
perfectly  distinct  change  may  be  propagated,  which  at  all  point'^  of  the 
fibre  at  which  it  arrives  sets  up  both  the  contraction  and  the  electrical 
change.  Such  direct  evidence,  however,  as  we  possess  goes  to  show 
that  it  is  the  electrical  disturbance  which  is  the  propagated  one,  and 
that  this  evokes  the  contractile  disturbance. 

There  is  ample  evidence  that  the  excitatory  electrical  response 
is  a  normal  physiological  phenomenon.  In  human  skeletal  muscles 
the  current  of  action  has  been  demonstrated  by  connecting  a  gal- 
vanometer with  ring  electrodes  passing  round  the  forearm,  and 
throwing  the  muscles  into  contraction.  A  diphasic  variation  is  thus 
obtained;  and  the  electrical  change  travels  with  a  velocity  of  as 
much  as  twelve  metres  per  second,  which  is  greater  than  the  velocity 
in  frogs'  muscles.  Electromotive  changes  are  likewise  associated 
with  the  beat  of  the  heart.  Action  currents  have  also  been  detected 
in  the  phrenic  nerves  of  living  animals  accompanying  the  respiratory 


THEORIES  OF  DEMARCATION  AND  ACTION  CURRENTS     8oi 


discharge  (Reid  and  Macdonald),  in  the  vagi  accompanying  the 
movements  of  the  lungs,  in  the  oesophagus  during  swallowing,  in 
the  cutaneous  sensory  nerves  in  response  to  the  '  adequate  '  stimulus 
of  pressure  (Stcinach),  in  the  retina  in  response  to  the  adequate 
stimulus  of  light,  in  glands  during  secretion,  in  the  central  nervous 
system  during  the  passage  of  impulses  along  its  conducting  paths. 
Some  of  these  will  be  further  considered  a  little  later  on. 

As  to  the  interpretation  of  the  facts  we  have  been  describing, 
and  which  are  summed  up  in  the  three  propositions  on  p.  796,  two 
cliief  doctrines  long  divided  the  ph^^siological  world:  (i)  the  theory  of 
du  Bois-Reymond,  the  pioneer  of  electro-physiology,  and  (2)  the  theory 
of  Hermann.  It  was  believed  by  du  Bois-Reymond  that  the  current 
of  rest  seen  in  injured  tissues  is  of  deep  physiological  import,  and  that 
the  electrical  difference  which  gives 
rise  to  it  is  not  developed  by  the 
lesion  as  such,  but  only  unmasked 
when  the  electrical  balance  is  upset 
by  injury.  He  looked  upon  the 
muscle  or  nerve  as  built  up  of  elec- 
tromotive particles,  with  definite 
positive  and  negative  surfaces  ar- 
ranged in  a  regular  manner  in  a  sort 
of  ground-substance  which  is  elec- 
trically indifferent.  The  '  negative 
variation'  he  supposed  to  depend  on 
an  actual  diminution  of  previously 
existing  electromotive  forces;  and 
from  this  conception  arose  its  his- 
toric name.  Hermann  and  his  school 
assumed  that  the  uninjured  muscle 
or  nerve  is  '  streamless, '  not  because 
equal  and  opposite  electromotive 
forces  exactly  balance  each  other  in 
the  substance  of  the  tissue,  but  be- 
cause electromotive  forces  are  absent 
until  they  are  called  into  existence 
(by  chemical  changes)  at  the  boun- 


Fig  292. — Upper  Curve,  Record  of  the 
Electrical  Changes  in  the  Vagus 
Nerve  (so-called  '  Electrovagogram  '), 
taken  with  the  String  Galvanometer. 
The  small  waves  on  it  are  synchronous 
with  the  heart-beats,  while  the  large 
waves  are  synchronous  with  the  respi- 
ratory movements,  the  mechanical 
record  of  which  constitutes  the 
second  curve  (ascent,  inspiratioi  ). 
The  lowest  curve  is  a  mechanical 
record  of  the  pulse  (Einthoven). 


dary,  or  plane  of  demarcation,  be- 
tween sound  and  injured  tissue.  For  this  reason  du  Bois-Reymond's 
current  of  rest  is  called  in  the  terminology  of  Hermann  the  '  demarca- 
tion '  current. 

The  newer  theories,  such  as  Macdonald"s,  have  sought  to  take  account 
of  the  recent  developments  of  physical  chemistry,  and  it  is  unquestion- 
able that  it  is  here  the  real  explanation  is  to  be  found.  There  is  little 
doubt  that  the  electrical  phenomena  of  the  tissues  are  connected  with 
the  existence  in  them  of  membranes,  envelopes,  or  sheaths,  physiological 
if  not  always  anatomical,  which  are  relatively  impermeable  to  certain 
ions.  When  such  a  sheath  is  injured,  these  ions,  carrying  with  them 
their  electrical  charges,  may  be  supposed  to  migrate  with  abnormal 
freedom  through  the  injured  part.  A  new  distribution  of  electricity  is 
thus  established  in  the  tissue,  and  differences  of  potential  depending 
upon  differences  in  the  concentration  of  the  ions  at  different  points  are 
set  up.  Bernstein  and  Tschermak,  from  an  investigation  of  the  thermo- 
dynamic relations  of  bio-electrical  currents,  have  come  to  the  conclusion 
that  they  are  analogous  to  the  currents  produced  by  so-called  concentra- 

51 


802  ELECTRO-PHYSIOLOGY 

tion  cells — 7.e.,  arrangements  of  solutions  of  electrolytes  of  different 
concentration  in  contact  with  each  other.  Since  the  development  of 
the  new  electrical  condition  depends  upon  the  fundamental  structure 
of  the  tissue,  these  modern  views  lead  us  back  to  du  Bois-Reymond's 
doctrine  of  a  pre-existing  electrical  equilibrium  connected  with  the 
essential  physiological  properties  of  muscle  or  nerve.  But  instead  of 
his  electromotive  elements  and  their  definite  arrangement,  we  have 
the  ions  and  their  definite  relation  to  the  semi-permeable  membranes. 

Relation  between  the  Action  Current  and  Functional  Activity. — 
Although  the  negative  variation  is  so  general  an  accompaniment  of 
excitation,  and  is  even  within  tolerably  wide  limits,  in  muscle  and  nerve 
at  least,  pretty  nearly  proportional  to  the  strength  of  the  stimulus,  it 
is  at  present  impossible  to  say  definitely  what  the  chemical  or  physical 
changes  are  which  underlie  it.  Unquestionably  the  electrical  changes 
are  closely  related  to  the  excitatory  process  and  to  the  functional 
activity  of  the  tissues.  In  the  case  of  nerve  some  writers,  indeed, 
assume  that  the  redistribution  of  potential  associated  with  the  excited 
state  is  identical  with  the  nervous  impulse,  but  the  common  view  is 
that  the  negative  variation  is  an  accompaniment  of  some  other  change 
which  constitutes  the  propagated  disturbance.  There  is  at  present  no 
clear  experimental  evidence  sufficient  to  decide  the  question.  From 
time  to  time  attempts  have  been  made  to  show  that  the  two  processes 
can  be  dissociated,  but  none  of  the  experiments  so  far  reported  are 
really  crucial. 

Like  the  demarcation  current,  the  action  current  and  the  excitation 
which  accompanies  it  may  be  due  to  changes  in  the  permeability  of 
membranes  or  changes  in  the  concentration  of  certain  ions. 

Although  the  electromotive  changes  caused  by  excitation  are  much 
more  transient  than  those  caused  by  injury,  everything  suggests  that 
there  must  be  some  deep  analogy  between  the  two  conditions.  Some 
have  supposed  that  what  may  be  called  a  subdued  and  more  or  less 
permanent  excitation  exists  in  the  neighbourhood  of  the  injured  tissue, 
an  excitation  which,  like  some  other  forms,  does  not  spread,  and  that 
this  explains  the  similarity  of  electrical  condition  in  activity  and  injury. 

It  is,  of  course,  clear  that  energy  must  be  transformed  to  produce  an 
electromotive  force  capable  of  doing  work.  It  may  be  assumed  that 
this  energy  is  ultimately  derived  from  the  stock  of  chemical  energy  in 
the  tissue-substance.  But  whether  in  the  final  transformation  the 
electrical  phenomena  are  the  expression  of  chemical  changes  or  of 
physical  (osmotic)  changes,  or  of  both,  we  do  not  know.  In  the  case  of 
muscle  it  is  possible  that  the  liberation  of  lactic  acid,  which  there  are 
several  reasons  for  regarding  as  essentially  concerned  in  the  initiation 
of  the  mechanical  change,  is  associated  in  some  v/ay  with  the  appearance 
of  the  negative  variation.  It  is  known  that  the  latter,  although  it 
begins  before  the  contraction,  and  very  rapidly  reaches  its  maximum, 
declines  more  gradually,  so  that  it  overlaps  the  mechanical  change  of 
form.  This  is  particularly  well  seen  in  veratrinized  muscles  (p.  729),  in 
which  the  electrical  variation,  like  the  contraction,  is  greatly  prolonged 
(Garten). 

Polarization  of  Muscle  and  Nerve. — We  have  already  spoken  of 
electrical  excitation  and  of  the  changes  of  excitability  caused  by 
the  passage  of  a  constant  current  (p.  759).  We  are  now  to  see  that 
these  physiological  effects  are  accompanied  by,  and  indeed  very 
closely  related  to,  more  physical  changes  which  the  galvanometer 
or  electrometer  reveals  to  us.     Since  these  throw  light  on  the 


ELECTROTONIC  CURRENTS  803 

physical,  and  therefore  ultimately  on  the  physiological,  structure  of 
the  tissues,  they  have  been  deeply  studied,  especially  in  nerve. 
There  is  no  question  that  they  depend  upon  the  presence  in  the 
tissues  of  membranes  presenting  a  relatively  great  resistance  to  the 
passage  of  ions.  When  a  current  is  passed  by  means  of  unpolarizable 
electrodes  (Fig.  230,  p.  705)  through  a  muscle  or  nerve  for  several 
seconds,  and  the  tissue  connected  to  the  galvanometer  immediately 
after  this  polarizir.g  current  is  opened,  a  deflection  is  seen  indicating 
a  current  (negative  polarization  current)  in  the  opposite  direction. 

This  (negative)  polarization,  like  the  polarization  of  the  electrodes 
seen  after  passage  of  a  current  through  any  ordinary  electrolytic  con- 
dJictor,  dilute  sulphuric  acid,  e.g.,  depends  on  the  liberation  of  ions 
(p.  423)  at  the  katliodc  and  anode.  It  is  seen  not  only  in  muscle,  nerve, 
and  other  animal  tissues,  but  also  in  vegetable  structures,  and  indeed, 
to  a  certain  extent,  in  unorganized  porous  bodies  soaked  with  electro- 
lytes. In  muscle  and  nerve,  however,  it  is  particularly  well  marked; 
and  although  it  is  not  bound  up  with  the  life  of  the  tissue,  and  may  be 
obtained  when  this  has  become  quite  inexcitable,  it  is  nevertheless 
dependent  on  the  preservation  of  the  normal  structure,  for  a  boiled 
muscle  shows  but  little  negative  polarization. 

When  the  polarizing  current  is  strong,  and  its  time  of  closure  short, 
we  obtain,  on  connecting  the  tissue  with  the  galvanometer  after  opening 
the  current,  not  a  negative,  but  a  positive  deflection,  indicating  a 
current  in  the  same  direction  as  that  of  the  polarizing  stream.  This  is 
really  an  action  stream,  due  to  the  opening  excitation  set  up  at  the 
anode  (p.  715).  It  is  only  obtained  when  the  tissue  is  living,  and  is  far 
more  strongly  marked  in  the  anodic  than  in  the  kathodic  region. 

Suppose  that  the  nerve  in  Fig.  293  is  stimulated  by  the  opening  of 
the  battery  B,  and  that,  immediately  after,  the  nerve  is  connected  with 
the  galvanometer  G  by  the  electrodes  E,  E^.  Suppose,  further,  that 
the  shaded  region  near  the  anode  remains  more  excited  for  a  short  time 
than  the  rest  of  the  nerve,  and  we  have  seen  (p.  761)  that  after  the 
opening  of  a  strong  current  there  is  a  defect  of  conductivity,  especially 
in  the  neighbourhood  of  the  anode,  which  would  tend  to  localize  excita- 
tion. An  action  current  will  pass  through  the  galvanometer  from  Fx 
to  E,  and  through  the  nerve  in  the  same  direction  as  the  original  stimu- 
lating stream.  Under  certain  conditions  a  state  of  continuous  excita- 
tion in  the  anodic  region  of  a  nerve  is  shown  by  a  tetanus  of  its  muscle 
{Rater's  tetanus,  p.  715,  and  Fig.  294). 

Electrotonic  Currents. — If  a  current  be  passed  from  the  battery 
through  a  medullated  nerve  (Fig.  295)  in  the  direction  indicated  by 
the  arrows,  while  a  galvanometer  is  connected  with  either  of  the 
extrapolar  areas,  as  shown  in  the  figure,  a  current  will  pass  through 
the  galvanometer,  in  the  same  direction  in  the  nerve  as  the  polar- 
izing current,  so  long  as  the  latter  continues  to  flow. 

These  currents  are  called  electrotonic  (in  the  kathodic  region  katelectro- 
tonic  ,  in  the  anodic,  anelectrotonic).  The  exact  mode  of  their  produc- 
tion is  obscure.  Similar  currents  can  be  detected  in  artificial  models 
consisting  of  a  good  conducting  core  and  a  badly  conducting  envelope; 
for  example,  a  platinum  wire  in  a  glass  tube  filled  with  saturated  zinc 
sulphate  solution,  or  a  zinc  wire  covered  with  cotton-wool  soaked  in 
salt  solution.     In  such  models  it  appears  to  be  essential  that  there 


8o4 


ELECT  RO'PH  YSIOLOG  Y 


should  be  polarization  (separation  of  ions)  at  the  bounaary  between 
the  core  and  the  sheath — i.e.,  between  the  wire  and  the  liquid,  where 
the  current  passes  from  the  one  to  the  other. 

A  current  led  inlc  the  sheath  tries,  so  to  speak,  to  pass  mostly  by 
the  good  conducting  wire.      If  this  is  not  polarizable — if  it  is,  e.g.,  a 


Fig.  293.— Diagram  to  show  Dis- 
tribution of  '  Positive  Polar- 
zation '  after  opening  Polar- 
izing Current.  B,  battery; 
G,  galvanometer.  The  dark 
shading  signifies  that  the  ex- 
citation to  which  the  current 
causing  the  positive  deflection 
after  the  opening  of  the  polar- 
izing current  is  due  is  greatest 
in  the  immediate  neighbour- 
hood of  the  anode,  and  fades 
away  in  the  intrapolar  region. 
+  indicates  the  anode,  and 
-  the  kathode  of  the  polariz- 
ing current. 


Fig.  294. — Ritter's  Tetanus. 
A  strong  voltaic  current 
was  passed  for  some  time 
through  the  nerve  of  a 
muscle-- nerve  preparation. 
On  opening  the  circuit,  the 
muscle  gave  one  strong  con- 
traction, and  then  entered 
into  irregular  tetanus,  which 
continued  for  four  minutes, 
(Only  the  first  part  of  the 
tracing  is  reproduced.) 


zinc  wire  surrounded  by  saturated  zinc  sulphate  solution — there  is 
little  or  no  spreading  of  the  current  outside  the  electrodes:  it  passes  at 
once  into  the  core,  and  so  on  to  the  othec  electrode.  If,  however,  there 
is  polarization  when  the  current  passes  from  the  liquid  mto  the  wire, 
as  is  the  case  in  the  platinum-zinc  sulphate  or  the  zinc-sodium  chloride 

combinations,  the  stream 
spreads  longitudinally  in 
the  sheath,  since  the 
polarization  introduces  a 
virtual  resistance  at  the 
surface  of  the  wire,  in 
comparison  with  which 
the  difference  in  resis- 
tance of  an  oblique  and  a 
direct  transverse  path 
through  the  liquid  becomes  small.  It  has  been  supposed  that  in 
meduUated  nerve  a  similar  polarization  takes  place  at  the  boundary 
between  some  part  of  the  nerve-fibre  which  may  be  called  a  core,  and 
another  part  wliich  may  be  called  a  sheath — for  instance,  between  the 
axis-cylinder  and  the  medullary  sheath,  or  between  the  latter  and  the 
neurilemma.     It  is  known  that  the  electrical  resistance  of  nerve  in  the 


-eh,  ,x,-jiiu,  ^o^ 


Fig.  295. — Diagram  showing  Direction  of  the  Extra- 
polar  Electrotonic  Currents,  -f  is  the  anode 
and  -  the  kathode  of  the  polarizing  current. 


ELECTROTONIC  CURRENTS  805 

transverse  direction  is  much  greater  (five  to  seven  times)*  than  the 
longitudinal  resistance.  Since  a  rapidly-established  polarization  would, 
by  the  ordinary  methods  of  measurement,  appear  as  a  resistance,  this 
has  been  adduced  as  evidence  of  the  great  capacity  of  nerve  for  polar- 
ization by  a  current  passing  across  the  fibres.  It  is,  however,  probable, 
from  what  we  know  of  the  high  electrical  resistance  of  the  physiological 
envelopes  of  such  cells  as  the  red  blood-corpuscles  (p.  26),  that  the 
great  transverse  resistance  of  nerve,  and  indeed  the  electrotonic  currents, 
are  due  in  part,  if  not  wholly,  to  the  true  resistance  of  one  or  more  of 
its  envelopes  (perhaps  the  medullary  sheath).  Examples  of  such 
differences  of  resistance  even  in  the  fluid  constituents  of  one  and  the 
same  animal  structure  arc  not  wanting.  For  instance,  the  specific 
resistance  of  the  yolk  of  a  hen's  egg  may  be  three  times  greater  than 
that  of  the  white. 

The  electrotonic  currents  cannot  spread  beyond  a  ligature ;  they  are 
stopped  by  anything  which  destroys  the  structure  of  the  tissue;  they 
are  affected  by  various  reagents.  But  this  docs  not  prove  that  they 
are  other  than  physical  in  origin,  for  what  destroys  the  structure  of 
the  tissue  or  modifies  its  molecular  condition  may  destroy  or  diminish 
its  capacity  for  polarization,  or  alter  its  electrical  resistance. 

There  are,  however,  certain  facts  which  indicate  that  physiological 
factors,  as  well  as  physical,  are  concerned.  While  the  currents  obtained 
from  core-models  show  a  general  resemblance  to  the  electrotonic  currents 
of  medullated  nerve,  there  is  one  significant  difference :  in  the  former  the 
katelectrotonic  and  anelectrotonic  currents  are  of  equal  intensity;  in 
the  latter  the  anelectrotonic  preponderates.  The  most  probable  ex- 
planation is  that  the  anelectrotonic  current  of  medullated  nerve  is  made 
up  of  two  distinct  electrical  effects,  one  physiological  in  nature,  the  other 
dependent  merely  on  the  structure  and  physical  properties  of  the  fibres, 
while  the  katelectrotonic  current  is  wholly  physical.  It  is  in  favour  of 
this  hypothesis  that  under  the  influence  of  ether,  which  abolishes  the 
physiological  functions  of  nerve,  the  anelectrotonic  current  diminishes 
till  it  becomes  equal  to  the  kateletrotonic.  Non-medullated  nerves,  in 
wliich  the  conditions  for  physical  electrotonus,  if  present  at  all,  are  only 
feebly  developed,  and  which  exhibit  no  katelectrotonic  current,  or  only 
a  very  weak  one,  show  an  anelectrotonic  current,  which  is  abolished  by 
ether,  and  seems  to  represent  the  physiological  portion  of  the  anelectro- 
tonic current  of  medullated  nerve. 

A  nerve  may  be  stimulated  by  an  electrotonic  current  produced 
in  nerve-fibres  lying  in  contact  with  it.  A  well-known  illustration 
of  this  is  the  experiment  known  as  the  paradoxical  contraction 
(Practical  Exercises,  p.  816). 

The  current  of  action  of  a  nerve  can  also  stimulate  another  nerve 
when  tlic  excitability  of  both  is  greater  than  normal,  as  is  the  case 
in  the  nerves  of  frogs  kept  in  the  cold.  This  comes  under  the  head 
of  secondary  contraction.  But  the  best-known  form  of  secondary 
contraction  is  where  ifc-nerve,  placed  on  a  muscle  so  as  to  touch  it  in 
two  points  (Fig.  296),  is  stimulated  by  the  action-current  of  the 
muscle,  and  causes  its  own  muscle  to  contract.     A  secondary  tetanus 

*  Since  a  part  of  the  current  is  conducted  by  the  connective  ti.ssue  and 
other  structures  lying  between  the  nervc-fibrcs,  and  the  longitudinal  and 
transverse  resistance  of  these  tissues  may  be  supposed  equal,  the  disproportion 
between  the  longitudinal  and  transverse  resistance  of  the  nerve  fibres  them- 
selves is  probably  much  greater  than  this. 


8o6 


ELECTRO-PHYSIOLOGY 


can  be  obtained  in  this  way  by  dropping  a  nerve  on  an  artificially 
tetanized  muscle.  The  beat  of  the  heart  causes  usually  only  a 
single  secondary  contraction  when  the  sciatic  nerve  of  a  frog  is 
allowed  to  fall  on  it  (p.  201).  But  when  the  diphasic  variation  is 
well  marked,  as  it  is  in  an  uninjured  heart,  there  may  be  a  secondary 

contraction   for  each  phase —  ^  _^^    , 

i.e.,  two  for  each  heart-beat.   ^' A       ^       /V     f^'"  "^ 

Excitation  of  one  muscle  may  in   .  ,/  /     \/ 

the  same  way  cause  secondary    ^        '^         '♦— — I 
contraction    of    another    with   ~-^^^  JLw 

which  it  is  in  close  contact.  IHHH^  JT 


^ 


^: 


Fig.  296.  —  Secondary  Contrac- 
tion. The  nerve  of  muscle  M 
touches  muscle  M'  at  a  and  b. 
Stimulation  of  the  nerve  of  M' 
at  S  causes  contraction  of  M. 


r.^  :  ,;.  —  Elf^trometer  Record  from  Rab- 
bit s  Heart  (Gotch).  The  heart  was  ex- 
posed and  beating  in  situ.  Contacts,  one 
on  base  of  right  ventricle,  the  other  on 
right  apex.  The  commencement  of  the 
beat  is  on  the  left-hand  edge  of  the  dark 
line  V.  The  length  of  the  dark  line  shows 
the  duration  of  the  beat.  Upward  move- 
ment signifies  relative  negativity  (activity) 
of  the  part  at  or  near  the  base  contact. 
Time-trace  at  top,  one-fifth  second. 


The  electromotive  phenomena  of  the  heart  and  of  the  central  ner- 
vous system  are  naturally  included  under  those  of  muscle  and  nerve. 

Heart. — Records  of  the  electrical  changes  obtained  with  the 
capillary  electrometer  or  string  galvanometer  from  the  exposed 
ventricles  vary  in  certain  details  with  the  position  of  the  two 
contacts.  When  one  contact  is  on  the  base  of  the  ventricles  (in  the 
rabbit)  near  the  auriculo-ventricular  groove,  and  the  other  on  the 
apex  (Fig.  297),  for  each  beat  of  the  ventricle  the  electrometer  record 
shows  (i)  a  sharp  rise,  indicating  relative  negativity  (activity)  of 
the  base;  (2)  an  equally  sharp  fall,  indicating  ffelative  negativity  at 
the  apex;  (3)  a  slower  but  marked  rise,  indicating  an  increase  or  a 
fresh  development  of  relative  negativitj^  at  the  base;  (4)  a  more 
rapid  fall,  which  returns  first  slowly,  then  quickly,  until  (i)  follows 
again  (Gotch).  The  time  between  the  beginning  and  the  top  of 
rise  (i)  is  b  "lieved  to  correspond  to  the  time  of  transmission  of  the 


ELECTRO-CARDIOGRAM 


807 


active  state  from  the  base  to  the  apex.  The  rate  of  propagation 
on  the  rabbit's  ventricle  varies  from  i  to  3  metres  a  second,  accord- 
ing to  the  rate  of  the  heart-beat.  Such  observations  have  been  inter- 
preted as  indicating  that  the  excitation,  with  its  accompanying 
electrical  change,  begins  at  the  base,  then  develops  in  the  region  of 
the  apex,  and  finally  involves  the  poition  of  the  ventricles  near  the 
aorta  and  pulmonary  artery,  possibly  extending  even  into  the  roots 
of  these  vessels.  The  full  explanation  of  this  seemingly  erratic 
course  of  the  excitation  wave  is  doubtless  dependent  upon  a  full 
knowledge  of  the  course  and  connections  of  the  conducting  system. 


■fpifiii 


1,  .  ,^iirv^fi«;vjifcv  usi»T^'-ii- 


Fig.  293. — Electrometer  Record  from  Tortoise  Heart  (Gotch).  One  contact  upon 
the  sinus,  the  other  on  the  apex  of  the  ventricle.  One  complete  beat  shown. 
Upward  movement  signifies  relative  negativity  of  the  sinus  contact.  The  dark 
line  A  shows  the  auricular  effect,  and  the  dark  line  V  the  ventricular  effect. 
Time-trace  at  top,  one-fifth  second. 

and  this  we  do  not  possess  as  yet.  The  fact  that  the  ventricle  is 
originally  developed  from  a  tube  with  a  venous  and  an  arterial  end, 
and  that  this  tube  later  on  becomes  bent  upon  itself  so  that  the  two 
ends  (the  auricular  or  venous  and  the  aortic  or  arterial)  lie  together 
at  the  base  of  the  ventricle,  probably  affords  the  clue.  It  should 
be  mentioned,  however,  that  this  explanation  of  the  second  rise  of 
the  ventricular  curve  (the  T-wave,  according  to  Einthoven's  nomen- 
clature. Fig.  304)  is  by  no  means  universally  accepted.  Einthoven, 
who  has  worked  with  the  string  galvanometer,  believes  that  be- 
tween the  first  (R)  and  the  second  (T)  ventricular  waves  the  whole 
of  the  ventricle  is  in  contraction,  and  that  there  is  no  difference  of 


8o8 


ELECTRO-PHYSIOLOG  Y 


Fig.  299. — Electro-Cardiograms  from  Man 
(Capillary  Electrometer)  (Einthoven  and 
Lint).  Obtained  from  the  same  individual 
at  rest  (upper  curve),  and  immediately  after 
vigorous  muscular  exercise  (lower  curve). 
The  elevations  A,  C,  D,  indicate  negativity 
of  base  to  apex;  the  notches  B  and  Cj,  nega- 
tivity of  apex  to  base. 


potential  at  this  time  between  its  various  parts.     The  T-wave  he 
considers  to  be  produced,  when  it  is  present,  merely  because  the 

excitated  state  does  not  dis- 
appear simultaneously  over 
the  whole  ventricle. 

In  the  ventricle  of  the 
frog  and  tortoise  the  same 
order  of  development  of  the 
negative  change  is  seen,  the 
base  first  becoming  rela- 
tively negative,  then  the 
apex,  and  then  the  neigh- 
bourhood of  the  origin  of 
the  aorta  (Fig.  298). 

Under  certain  conditions 
the  action  current  of  the  heart 
may  stimulate  the  phrenic 
nerves,  causing  the  dia- 
phragm to  contract  synchro- 
nously with  the  heart. 

The  Human  Electro- Cardi- 
ogram.— An  electrical  change 
accompanies  each  beat  of  the  human  heart.     Waller  first  show^ed  how 
this  may  be  demonstrated  by  means  of  the  capillary  electrometer. 

Einthoven  and 
Lint  then  investi- 
gated the  pheno- 
menon on  a  large 
numberof  persons. 
From  the  photo- 
graphic records  of 
the  movements  of 
the  meniscus  they 
constructed  the 
true  electro  -  car- 
diographic  curves* 
(Fig.  300),  which 
express  the  actual 
changes  in  the  po- 
tential difference 
between  the  two 
points  led  off. 
They  distinguished 
in  every  one  of 
these  constructed 
electro-cardio- 
grams five  points 
or  cusps,  three  of 
which  indicate  re- 
lative    negativity 


.\.... 


F"ig.  300. — Constructed  Elec- 
tro-Cardiograms from  Man 
(EinthovenandLint).  Time 
is  laid  off  along  the  hori- 
zontal, and  electromotive 
force  along  the  vertical  axis, 
the  same  sjtacc  being  allot- 
ted to  ten  millivolts  {i.e., 
yJj  volt)  as  to  one  second. 


Fig.  301.  —  illustrating  the 
Position  of  Favourable  and 
Unfavourable  Leads  for 
the  Human  Electro- 
Cardiogram  (Waller). 


♦  In  all  accurate  work  with  the  capillary  electrometer  such  curves  must  be 
obtained  by  construction  from  the  direct  photographic  records,  which  do  not 
themselves  give  an  absolutely  true  picture  of  the  variations. 


ELECTRO-CA  RDIOQRA  M 


809 


of  tlie  base  of  the  heart  to  the  apex,  and  two  negativity  of  the  apex  to 
the  base.  The  capillary  electrometer  has  now  been  superseded  by  the 
string  galvanometer  (p.  700)  for  the  investigation  of  the  human  electro- 
cardiogram (Figs.  302-305).  But  a  sample  of  the  records  obtained  by 
the   former   method    (Fig.    299),  witli    the   corresponding  constructed 


Fig.  302. — Human  Electro-Cardiogram 
(String  Galvanometer)  (Einthoven). 
Led  off  from  the  two  hands,  i  mm. 
of  the  abscissa  corresponds  to  001 
second. 


Fig.  303. — Human  Electro-Cardio- 
gram (String  Galvanometer) 
(Einthoven).  Led  off  from  right 
hand  and  left  foot. 


9,1  Sec 


Fig.  304. — Schematic  Representation  of  Electro-Cardiogram  (String  Galvanometer) 
(Einthoven).  Five  points  are  lettered  at  which  the  curve  changes  sign.  P  cor- 
responds to  the  auricular  contraction;  the  other  four  are  included  in  the  ven- 
tricular cycle. 


Fig-  305- — Electro-Cardiogram  from  Man  (String  Galvanometer)  (Lewis).  From  a 
case  of  paro.xysmal  tachycardia.  The  heart-rate  was  200  a  minute.  The  upper 
notched  line  is  the  time-trace  in  one-fifth  seconds. 


electro-cardiograms,  (Fig.  300)  is  reproduced  for  their  historical  interest. 
In  their  main  features  it  is  obvious  that  t-liey  agree  with  the  records 
obtained  by  the  string  galvanometer.  The  electro-cardiograms  are 
distinctly  affected  by  exercise  and  by  the  position  of  the  body,  and  very 
markedly  in  disease.    The  galvanometer  may  be  connected  with  the  two 


8io  ELECTRO-PHYSIOLOGY 

hands,  or,  better,  with  the  ri^ht  hand  and  the  left  foot.  The  two  feet 
are  the  most  unfavourable  combination.  The  reason  is  obvious  from 
the  direction  of  the  long  axis  of  the  heart,  which  determines  the 
direction  of  the  lines  of  flow  of  currents  due  to  differences  of  potential 
between  base  and  apex  (Fig.  301). 

Central  Nervous  System. — It  was  discovered  by  du  Bois-Reymond 
that  the  spinal  cord,  like  a  nerve,  shows  a  current  of  rest  between  longi- 
tudinal surface  and  cross-section,  and  that  a  current  of  action  is  caused 
by  excitation.  Setschenow  stated  that  when  the  medulla  oblongata 
of  the  frog  was  connected  with  a  galvanometer,  spontaneous  variations 
occurred  which  he  supposed  due  to  periodic  functional  changes  in  its 
grey  matter.  Gotch  and  Horsley  have  made  experiments  on  the  spinal 
cords  of  cats  and  monkeys.  Leading  off  from  afn  isolated  portion  of 
the  dorsal  cord  to  the  capillary  electrometer,  and  stimulating  the 
'  motor  '  region  of  the  cortex  cerebri,  they  obtained  a  persistent  nega- 
tive variation  followed  by  a  series  of  intermittent  variations.  This 
agrees  remarkably  with  the  muscular  contractions  in  an  epileptiform 
convulsion  started  by  a  similar  excitation  of  the  cortex,  which  consist 
of  a  tonic  spasm  followed  by  clonic  or  phasic  (interrupted)  contractions. 
By  means  of  the  galvanometer,  the  same  observers  have  made  in- 
vestigations on  the  paths  by  which  impulses  set  up  at  different  points 
travel  along  the  cord.  To  these  we  shall  have  to  refer  again  (p.  867). 
Electrical  Phenomena  of  Glands. — These  have  been  studied  with  any 
care  chiefly  in  the  submaxillary  gland  and  in  the  skin,  although  the 
liver,  kidney,  spleen,  and  other  organs  also 
show  currents  when  injured.  In  the  sub- 
maxillary gland  the  hilus  is  galvanometrically 
positive  to  any  point  on  the  external  surface 
of  the  gland ;  a  current  passes  from  hilus  to 
surface  through  the  galvanometer,  and  from 
surface  to  hilus  through  the  gland  (Fig.  306). 
Fig.  306. — Current  of  Sub-  When  the  chorda  tympani  is  stimulated  with 
maxillary  Gland.  rapidly  -  succeeding      shocks      of      moderate 

strength,  there  is  a  positive  variation — i.e.,  the 
hilus  becomes  still  more  positive  to  the  surface.  This  variation  can 
be  abolished  by  a  small  dose  of  atropine. 

Skin  Currents. — So  far  as  has  been  investigated,  the  integument  of  all 
animals  shows  a  permanent  current  passing  in  the  skin  from  the  external 
surface  inwards.  This  is  feebler  in  skin  which  possesses  no  glands.  In 
skin  containing  glands  the  current  is  chiefly,  but  not  altogether,  secre- 
tory. As  such,  it  is  affected  by  influences  which  affect  secretion,  a 
positive  variation  being  caused  by  excitation  of  secretory  nerves — e.g., 
in  the  pad  of  the  cat's  foot  by  stimulation  of  the  sciatic.  The  deflection 
obtained  when  a  finger  of  each  hand  is  led  off  to  the  galvanometer, 
which  was  at  one  time  looked  upon  as  a  proof  of  the  existence  of  currents 
of  rest  in  intact  muscles,  is  due  to  a  secretion  current. 

Of  more  doubtful  origin  is  the  current  of  ciliated  mucous  membrane, 
which  has  the  same  direction  as  that  of  the  skin  of  the  frog  and  the 
mucous  membrane  of  the  stomach  of  the  frog  and  rabbit — viz.,  from 
ciliated  to  under  surface  through  the  tissue,  or  from  ciliated  surface  to 
cross-section,  if  that  is  the  way  in  which  it  is  led  off.  The  current  is 
strengthened  by  induction  shocks,  by  heating,  and  in  general  by  influ- 
ences which  increase  the  activity  of  the  ciUa.  Some  circumstances 
point  to  the  goblet-cells  in  the  membrane  as  the  source  of  the  current ; 
but,  on  the  whole,  the  balance  of  evidence  is  in  favour  of  the  cilia  being 
the  chief  factor  (Engelmann),  although  the  mucin-secreting  cells  may 
be  concerned,  too.     Electrical  changes  associated  with  secretion  have 


ELECTROMOTIVE  PHENOMENA  OF  THE  EYE 


8ii 


been  observed  in  the  frog's  1;ongue  on  excitation  of  the  glosso-pharyngeal 
nerve. 

Eye-Currents. — If  two  unpolarizable  electrodes  connected  with  a 
galvanometer  are  placed  on  the  excised  eye  of  a  frog  or  rabbit,  one  on 
the  cornea  and  the  other  on  the  cut  optic  nerve,  or  on  the  posterior 
surface  of  the  eyeball,  it  is  found  that  a  current  passes  in  the  eye  from 
optic  nerve  to  cornea,  the  fundus  of  the  eye  being  therefore  negative 
as  regards  the  cornea  (Fig.  307).  The  current  has  the  same  direction 
if  the  anterior  electrode  is  placed  on  the  an- 
terior surface  of  the  retina  itself,  the  front  of 
the  eyeball  being  cut  away,  or  if  one  electrode 
is  in  contact  with  the  anterior  and  the  ether 
with  the  posterior  surface  of  the  isolated 
retina.  There  is  nothing  of  special  interest  in 
this;  but  the  important  point  is  that  if  light  be 
now  allowed  to  fall  upon  the  eye,  or  upon  the 
isolated  retina,  characteristic  electrical  changes 
are  caused.  These  are  spoken  of  as  the  photo- 
electric reaction,  and  are  best  studied  by  means 
of  the  string  galvanometer.  The  features  of 
the  curve  representing  the  photo-electric  reaction  va,ry  with  the  duration 
and  intensity  of  the  illumination  and  with  the  previous  condition  of  the 
eye  as  regards  illumination.  A  careful  analysis  of  the  curves  obtained 
under  different  conditions  supports  the  hypothesis  that  there  occur  iff 
the  eye  three  separate  processes,  which  may  for  convenience  be  con- 
sidered to  depend  upon  the  existence  in  the  retina  of  three  separate 
photo-chemical  substances.  When  light  of  moderate  intensity  is 
allowed  to  act  upon  an  eye  which  has  not  shortly  before  been  exposed 


Fig.  307. — ii^ye-Curreat. 


Fig,  308.— Photo-Electric  Reaction  of  Frog's  Eye  (Einthoven  and  Jolly).  The 
duration  of  the  flash  (of  green  light)  waso-oi  second.  The  eye  had  been  pre- 
viously in  the  dark,  i  millimetre  of  the  abscissa  corresponds  to  05  second, 
I  millimetre  of  the  ordinate  to  10  microvolts.    Curve  to  be  read  from  left  to  right. 


to  strong  light,  a  form  of  curve  is  obtained  which  seems  to  represent 
the  combined  reaction  of  the  three  substances  (Einthoven  and  Jolly) 
(Fig.  308).  After  a  latent  period  a  small  preliminary  negative  deflec- 
tion A  is  observed  (downward  movement  of  the  string).  This  is  at  once 
followe  1  by  a  much  larger  upward  movement  (positive  variation)  in 
the  same  direction  as  the  resting  effect,  the  fundus  becoming  relatively 
more  negative  to  the  cornea  than  before.  After  the  peak  B  has  been 
reached,  the  curve  sinks  first  rapidly,  then  more  gradunlly.  but  soon 
mounts  again,  and  reaches  a  second  maximum  C,  which  is  higher  than  B 


8l2 


ELECTRO-PHYSIOLOGY 


(second  positive  variation).  Finally,  the  curve  descends  to  its  original 
level.*'  The  photo-electric  reaction  is  substantially  the  same  in  all 
vertebrate  eyes  hitherto  investigated.  In  the  cephalopcd  retina,  too, 
the  only  important  electrical  change  on  illumination  is  in  the  same 
direction  as  the  resting  effect. 

The  reaction  depends  upon  the  retina  alone,  and  does  not  occur 
when  it  is  removed.  Bleaching  of  the  visual  purple  does  not  much 
affect  it,  so  that  it  is  not  connected  with  chemical  changes  in  this 
substance.     Its  seat  must  be  the  layer  of  rods  and  cones,  since  in  the 


Fig.  309. — Diagram  showing  Direction  of  Shock  in  Gymnotus. 

cephalopods  the  structure  called  the  retina  contains  only  this  layer,  the 
other  layers  of  the  vertebrate  retina  being  represented  in  the  optic  nerve 
and  ganglion  (Beck) .  Of  the  spectral  colours,  yellow  light  causes  the 
largest  variation;  blue,  the  least;  but  white  light  is  more  powerful  than 
either  (Dewarand  McKendrick).  (For '  visual  purple,' see  Chap.  XVIII.) 
Electric  Fishes. — Except  lightning,  the  shocks  of  these  fishes  were 
probably  the  first  manifestations  of  electricity  observed  by  man.  The 
Torpedo,  or  electrical  ray,  of  the  coasts  of  Europe  was  known  to  the 
Greeks  and  Romans.     It  is  mentioned  in  the  writings  of  Aristotle  and 

Pliny,  and  had  the  honour  of 
being  described  in  verse  1,500 
years  before  Faraday  made  the 
first  really  exact  investigation 
of  the  shock  of  the  Gymnotus , 
or  electric  eel,  of  South  America. 
Another  of  the  electric  fishes, 
Malapterurus  electricus,  al- 
though found  in  many  of  the 
African  rivers,  the  Nile  in  par- 
ticular, and  known  forages,  was 
scarcely  investigated  till  fifty 
years  ago. 

In  all  these  fishes  there  is  a 
special  bilateral  organ  immediately  under  the  skin,  called  the  electrical 
organ.  It  is  in  this  that  the  shock  is  developed.  It  consists  of  a 
series  of  plates  arranged  parallel  to  each  other.  To  one  side  of  each 
plate  a  branch  of  the  electrical  nerve  supplying  each  lateral  half  of 
the  organ  is  distributed,  so  that  each  half  of  the  organ  represents  a 
battery  of  many  cells  arranged  in  series. 

In  Gymnotus  the  plates  are  vertical,  and  at  right  angles  to  the  long 
axis  of  the  fish,  and  the  nerves  are  distributed  to  their  posterior  surface; 

*  In  the  figure  the  last  portion  of  the  curve  while  it  is  still  slowly  descending 
has  not  been  reproduced. 


Fig. 


310. — Diagram   showing   Direction   of 
Shock  in  Malapterurus. 


ELECTRIC  FISHES  813 

the  shock  passes  in  the  animal  from  tail  to  head.  In  Malapterurus, 
although  the  direction  of  the  plates  is  the  same,  and  the  nerve-supply 
is  also  to  the  posterior  surface,  the  shock  passes  from  head  to  tail. 

In  Torpedo,  the  plates  or  septa  dividing  the  vertical  hexagonal  prisms 
of  which  each  lateral  half  of  the  organ  consists  are  horizontal ;  the  nerve- 
supply  is  to  the  lower  or  ventral  surface ;  and  the  shock  passes  from  belly 
to  back  through  the  organ.  In  afl  electric  fishes  the  discharge  is  dis- 
continuous; an  active  fish  may  give  as  manj^  as  200  shocks  per  second. 

The  electrical  nerve  of  Malapterurus  is  peculiar.  It  consists  of  a 
single  gigantic  nerve-fibre  on  each  side,  arising  from  a  giant  nerve-cell. 
The  fibre  has  an  enormously  thick  sheath,  the  axis-cylinder  forming  a 
relatively  small  part  of  the  whole ;  and  the  branches  which  supply  the 
plates  of  the  organ  are  divisions  of  this  single  axis-cylinder. 

The  electromotive  force  of  the  shock  of  the  Gymnotus  may  be  very 
considerable;  and  even  Torpedo  and  Malapterurus  are  quite  able  to 
kill  other  fish,  their  enemies  or  their  prey.  Indeed,  Gotch  has  esti- 
mated the  electromotive  force  of  i  cm.  of  the  organ  of  Torpedo  at 
5  volts.  Schonlein  finds  that  the  electromotive  force  of  the  whole 
organ  may  be  equal  to  that  of  31  Daniell  cells,  or  0-08  volt  for  each 
plate,  and  it  is  one  of  the  mo-^t  interesting  questions  in  the  whole  of 
electro-physiolog\%  how  they  are  pro- 
tected from  their  own  currents.  There 
is  no  doubt  that  the  current  density 
inside  the  fish  must  be  at  least  as 
great  as  in  any  part  of  the  water  sur- 
rounding it,  and  probably  much 
greater.  The  central  nervous  system 
and  the  great  nerves  must  be  struck 
by  strong  shocks,  yet  the  fish  itself  is  Fig.  311.— Diagram  showing  Direc- 
not  injured ;  nay,  more,  the  young  in  tion  of  Shock  iu  Torpedo, 

the  uterus  of  the  viviparous  Torpedo 

are  unharmed.  The  only  explanation  seems  to  be  that  the  tissues  of 
electric  fishes  are  far  less  excitable  to  electrical  stimuli  than  the  tissues  of 
other  animals;  and  this  is  found  to  be  the  case  when  their  muscles  or 
nerves  are  tested  with  galvanic  or  induction  currents.  It  requires  ex- 
tremely strong  currents  to  stimulate  them ;  and  the  electrical  nerves  are 
more  easily  excited  mechanically,  as  by  ligaturing  or  pinching,  than  elec- 
trically. In  general,  too,  the  shock  is  more  readily  called  forth  by  reflex 
mechanical  stimulation  of  the  skin  than  by  electrical  stimulation.  But 
that  the  organ  itself  is  excitable  by  electricity  has  been  shown  by  Gotch. 
He  proved  that  in  Torpedo  a  current  passed  in  the  normal  direction 
of  the  shock  is  strengthened,  and  a  current  passed  in  the  opposite 
direction  weakened,  by  the  development  of  an  action  current  in  the 
direction  of  the  shock.  And,  indeed,  a  single  excitation  of  the  electrical 
nerve  is  followed  by  a  series  of  electrical  oscillations  in  the  organ,  which 
gradually  die  away.  The  latent  period  of  a  single  shock  is  about 
yjj  second.  The  skate  must  be  included  in  the  list  of  electric  fishes. 
Although  its  organ  is  relatively  small,  and  its  electromotive  force  rela- 
tively feeble,  yet  it  is  in  all  respects  a  complete  electrical  organ.  It 
is  situated  on  either  side  of  the  vertebral  column  in  the  tail.  The 
plates  or  discs  are  placed  transversely  and  in  vertical  planes.  The 
nerves  enter  their  anterior  surfaces ;  the  shock  passes  in  the  organ  from 
anterior  to  posterior  end.  Gotch  and  Sanderson  have  estimated  the 
maximum  electromotive  force  of  a  length  of  i  cm.  of  the  electrical 
organ  of  the  skate  at  about  half  a  volt. 

Whether  the  electrical  organ  is  the  homologue  of  muscle  or  of  nerve- 
ending,  or  whether  it  is  related  to  cither,  has  been  much  discussed. 
Our  surest  guide  in  a  question  of  this  sort  is  the  study  of  development ; 


8 14  ELECTRO-PHYSIOLOGY 

and  researches  along  this  line  have  shown  that  there  are  two  kinds  of 
electrical  organ,  one  being  modified  muscle  (as  in  Gymnotus,  Torpedo, 
and  the  skate);  the  other  transformed  skin-glands  (as  in  Malapterurus). 
The  scanty  blood-supply  of  the  electrical  organs  in  comparison  with 
that  of  muscle  is  noteworthy.  In  no  case  do  bloodvessels  enter  the  sub- 
stance of  the  plates. 


PRACTICAL  EXERCISES  ON  CHAPTER  XV. 

1 .  Galvani  's  Experiment. — Pith  a  frog  (brain  and  cord) .  Cut  through 
the  backbone  above  the  urostyle,  and  clear  away  the  anterior  portion 
of  the  body  and  the  viscera.  Pass  a  copper  hook  beneath  the  two 
sciatic  plexuses,  and  hang  the  legs  by  the  hook  on  an  iron  tripod.  If 
the  tripod  has  been  painted,  the  paint  must  be  scraped  away  where  the 
hook  is  in  contact  with  it.  Now  tilt  the  tripod  so  that  the  legs  come 
in  contact  with  one  of  the  iron  feet.  Whenever  this  happens,  the 
circuit  for  the  current  set  up  by  the  contact  of  the  copper  and  iron  is 
completed,  the  nerves  are  stimulated,  and  the  muscles  contract  (p.  795). 

2.  Make  a  muscle-nerve  preparation  from  the  same  frog.  Crush  the 
muscle  near  the  tendo  Achillis,  so  as  to  cause  a  strong  demarcation 
current.  Cut  off  the  end  of  the  sciatic  nerve.  Then  lift  the  nerve 
with  a  small  brush  or  thin  glass  rod,  and  let  its  cross-section  fall  on  or 
near  the  injured  part  of  the  muscle.  Every  time  the  nerve  touches  the 
muscle  a  part  of  the  demarcation  current  passes  through  it,  stimulates 
the  nerve,  and  causes  contraction  of  the  muscle  (p.  795). 

3.  Secondary  Contraction. — Make  two  muscle-nerve  preparations. 
Lay  the  cross-section  of  one  of  the  sciatic  nerves  on  the  muscle  of  the 
other  preparation  (Fig.  296,  p.  806).  Place  under  the  nerve  near  its 
cut  end  a  small  piece  of  glazed  paper  or  of  glass  rod,  and  let  the  longi- 
tudinal surface  of  the  nerve  come  in  contact  with  the  muscle  beyond 
this.  Lay  the  nerve  of  the  other  preparation  on  electrodes  connected 
with  an  induction  machine  arranged  for  single  shocks,  v/ith  a  Daniell 
cell  and  a  spring  key  in  the  primary  circuit  (Fig.  274,  p.  781).  On 
closing  or  opening  the  key  both  muscles  contract.  Arrange  the  induc- 
tion machine  for  an  interrupted  current.  When  it  is  tlirown  into  one 
nerve,  both  muscles  are  tetanized;  the  nerve  lying  on  the  muscle  whose 
nerve  is  directly  stimulated  is  excited  by  the  action  current  of  the  muscle. 

4.  Demarcation  Current  and  Current  of  Action  with  Capillary  Elec- 
trometer. —  {a)  Study  the  construction  of  the  capillary  electrometer 
(Fig.  227,  p.  702).  Raise  the  glass  reservoir  by  the  rack  and  pinion 
screw,  so  as  to  bring  the  meniscus  of  the  mercury  into  the  field.  Place 
two  moistened  fingers  on  the  binding-screws  of  the  electrometer,  open 
the  small  key  connecting  th^m,  and  notice  that  the  mercury'  moves,  a 
difference  of  potential  between  the  two  binding-screws  being  caused 
by  the  moistened  fingers. 

(6)  Demarcation  Current. — Set  up  a  pair  of  unpolarizable  electrodes 
(Fig.  230,  p.  705).  Fill  the  glass  tubes  about  one-third  full  of  kaolin 
mixed  with  physiological  salt  solution  till  it  can  be  easily  moulded. 
To  do  this,  make  a  piece  of  the  clay  into  a  little  roll,  which  will  slip  down 
the  tube.  Then  with  a  match  push  it  down  until  it  forms  a  firm  plug. 
Next  put  some  saturated  zinc  sulphate  solution  in  the  tubes,  above  the 
clay,  with  a  fine-pointed  pipette.  Fasten  the  tubes  in  the  holder  fixed 
in  the  moist  chamber  (Fig.  312).  Now  amalgamate  the  small  pieces  of 
zinc  wire  (p.  195)  which  are  to  be  connected  with  the  binding-screws  of 
the  chamber.  (Or  use  Porter's  '  boot  '  electrodes.  These  are  made  of 
unglazed  potter's  clay.  In  use  the  leg  of  the  boot  is  half-filled  with 
saturated  zinc  sulphate  solution,  into  which  dips  a  thick  amalgamated 


PRACTICAL  EXERCISES 


815 


zinc  wire.  In  the  foot  of  the  boot  is  a  hollow  (or  well)  which  is  filled 
with  physiological  salt  solution  and  serves  to  keep  the  feet  well  moist- 
ened with  the  salt  solution.  The  nerve  is  laid  on  the  feet  of  the  boots. 
When  not  in  use  the  boots  shoulfl  be  kept  in  physiological  salt  solution.) 

The  zincs  are  now  placed  in  the  tubes,  dipping  into  the  zinc  sulphate. 
A  piece  of  clay  or  blotting-paper  moistened  with  physiological  salt  solu- 
tion is  laid  across  the  electrodes  to  complete  the  circuit  between  their 
points,  and  they  are  connected  with  the  electrometer  to  test  whether 
they  have  been  properlj-  set  up.  There  ought  tc  be  little,  if  any,  move- 
ment of  the  mercury  on  opening  the  side-key  of  the  electrometer.  If  the 
movement    is     large,  __-===5 

the  electrodes  are 
'polarized,'  and  must 
be  set  up  again.  The 
second  pair  of  bind- 
ing -  screws  in  tlie 
chamber  are  con- 
nected with  a  pair  of 
platinum- pointed 
electrodes  on  the  one 
side,  and  on  the  other, 
through  a  short-cir- 
cuiting key,  with  the 
secondary  coil  of  an 
induction  machine  ar- 
ranged for  tetanus. 

Next  pitli  a  frog 
(cord  and  brain),  and 
make  a  muscle-nerve 
preparation.  Injure 
the  muscle  near  the 
tendo  Achillis.  Lay 
the  injured  part  over 
one  unpolarizable 
electrode,  and  an  un- 
injured part  over  the 
other.  Put  a  wet  sponge  in  the  chamber  to  keep  the  air  moist,  and  place 
the  glass  lid  on  it.  Focus  the  meniscus  of  the  mercury,  and  open  the 
key  of  the  electrometer;  the  mercury  will  moVe,  perhaps  right  out  of  the 
field.  Note  the  direction  of  movement,  and,  remembering  that  the 
real  direction  is  the  opposite  of  the  apparent  direction,  and  that  when 
the  mercury  in  the  capillary  tube  is  connected  with  a  part  of  the  muscle 
which  is  relatively  positive  to  that  connected  with  the  sulphuric  acid, 
the  movement  is  from  capillary  to  acid,  determine  which  is  the  galvano- 
metrically  positive  and  which  the  negative  portion  of  the  muscle  (p.  796). 

(c)  Action  Current. — Now,  without  disturbing  its  position  on  the 
electrodes,  fasten  the  muscle  to  the  cork  or  paraffin  plate  in  the  moist 
chamber  by  pins  thrust  through  the  lower  end  of  the  femur  and  the 
tendo  Achillis.  Lay  the  nerve  on  the  platinum  electrodes.  Open  the 
key  of  the  electrometer,  and  let  the  meniscus  come  to  rest.  This 
happens  very  quickly,  as  the  capillary  electrometer  has  but  little  inertia. 
If  the  meniscus  has  shot  out  of  the  field,  it  must  be  brouglit  back  by 
raising  or  lowering  the  reservoir.  Stimu]^te  the  nerve  by  opening  the 
key  in  the  secondary  circuit;  the  meniscus  moves  in  the  direction  oppo- 
site to  its  former  movement. 

{d)  Repeat  {b)  and  (c)  with  the  nerve  alone,  laying  an  injured  part 
(crushed,  cut,  or  overheated)  on  one  electrode,  aiid  an  uninjured  part 
on  the  other.     Of  course,  the  nerve  does  not  need  to  be  pinned. 


Fig.  312. — Moist  Chamber.  E,  unpolarizable  electrodes 
supported  in  the  cork  C;  M,  muscle  stretched  over  the 
electrodes  and  kept  in  position  by  the  pins  A,  B,  stuck 
in  the  cork  plate  P;  B,  binding-screws  connected  with 
galvanometer  or  capillary  electromoter.  The  othei 
pair  of  binding-screws  serves  to  connect  a  pair  of 
stimulating  electrodes  inside  the  chamber  with  the 
secondary  coil  of  an  induction  machine. 


8 1 6  ELECT RO-PH  YSl  OLOG  Y 

Clean  the  unpolarizable  electrodes,  and  be  sure  to  lower  the  reservoir 
of  the  electrometer;  otherwise  the  mercury  may  reach  the  point  of  the 
capillary  tube  and  run  out. 

In  4  a  galvanometer  (p.  699)  may  be  used  with  advantage  by  students, 
if  one  is  available,  instead  of  the  electrometer,  the  unpolarizable  elec- 
trodes being  connected  to  it  through  a  short-circuiting  key.  The  spot 
of  light  is  brought  to  the  middle  of  the  scale  by  moving  the  control- 
magnet;  or  if  a  telescope-reading  (Fig.  222,  p.  699)  is  being  used,  the 
zero  of  the  scale  is  brought  by  the  same  means  to  coincide  with  the 
vertical  hair-line  of  the  telescope.  The  short-circuiting  key  is  then 
opened. 

5.  Action  Current  of  Heart. — Pith  a  frog  (brain  and  cord).  Excise 
the  heart,  and  lay  the  base  on  one  unpolarizable  electrode,  and  the 
apex  on  the  other,  having  a  sufficiently  large  pad  of  clay  on  the  tips  of 
the  electrodes  to  insure  contact  during  the  movements  of  the  heart,  or 
having  little  cups  hollowed  in  the  clay  and  filled  with  physiological  salt 
solution,  into  which  the  organ  dips.  Connect  the  electrodes  with  the 
capillary  electrometer  and  open  its  key.  At  each  beat  of  the  heart  the 
mercury  will  move  (p.  806). 

.  6.  Electrotonus. — Set  up  two  pairs  of  unpolarizable  electrodes  in  the 
moist  chamber.  Connect  two  of  them  with  a  capillary  electrometer 
(or  galvanometer),  and  two  with  a  battery  of  three  or  four  small  Daniell 
cells,  as  in  Fig.  295.  Lay  a  frog's  nerve  on  the  electrodes.  When  the 
key  in  the  battery  circuit  is  closed,  the  mercury  (or  the  needle  of  the 
galvanometer)  moves  in  such  a  direction  as  to  indicate  that  in  the  extra- 
polar  regions  parts  of  the  nerve  nearer  to  the 
anode  are  relatively  positive  to  parts  more  re- 
mote, and  parts  nearer  to  the  kathode  are  rela- 
tively negative  to  parts  more  remote.  The 
direction  of  movement  of  the  mercury  (or  gal- 
vanometer needle)  must  be  made  out  first  for  one 
direction  of  the  polarizing  current.  Then  the 
latter  must  be  reversed,  and  the  movement  of 
the  mercury  (or  needle)  on  closing  it  again  noted 
(p.  803). 

7.  Paradoxical  Contraction. — Pith  a  frog  (brain 
and  cord).  Dissect  out  the  sciatic  nerve  down  to 
the  point  where  it  splits  into  two  divisions,  one 
for  the  gastrocnemius  b,  and  the  other  for  the 
peroneal  muscles  a.  Divide  the  peroneal  branch 
as  low  down  as  possible,  and  make  a  muscle-nerve 
preparation  in  the  usual  way.  Lay  the  central 
313 —Paradoxical  end  of  the  peroneal  nerve  on  electrodes  con- 
Contraction,  nected  through  a  simple  key  with  a  battery  of  two 
Daniell  cells.  When  the  peroneal  nerve  is  stimu- 
lated, the  gastrocnemius  muscle  contracts.  This  result  is  not  due  to  the 
current  of  action,  for  it  is  not  obtained  with  mechanical  stimulation 
of  the  nerve.  But  it  is  not  the  result  of  an  escape  of  current,  for  if  the 
peroneal  nerve  be  ligatured  between  the  point  of  stimulation  and  the 
bifurcation,  no  contraction  is  obtained.  The  contraction  is  really  due 
to  a  part  of  the  electrotonic  current  set  up  in  the  peroneal  nerve  passing 
through  the  fibres  for  the  gastrocnemius,  where  they  lie  side  by  side 
in  the  trunk  of  the  sciatic.     . 

8.  Alterations  in  Excitability  (and  Conductivity)  produced  in  Nerve 
by  the  Passage  of  a  Voltaic  Current  through  it. — Set  up  two  pairs  of 
unpolarizable  electrodes  in  the  moist  chamber.  Connect  a  battery  of 
two  or  three  Daniell  cells,  arranged  in  series  through  a  simple  key 


PkACTICAL  EXERCISES  817 

with  the  side-cups  of  a  Pohl's  commutator  with  cross-wires  in.  Con- 
nect the  commutator  to  one  pair  of  the  unpolarizable  electrodes  ('  the 
polarizing  electrodes  '),  as  in  Fig.  314.  The  other  pair  of  unpolarizable 
electrodes  ('  the  stimulating  electrodes  ')  are  to  be  connected  through  a 
short-circuiting  key  with  the  secondary  of  an  induction  machine 
arranged  for  tetanus.  A  single  Daniell  is  put  in  the  primary  coil. 
Pith  a  frog  (brain  and  cord),  make  a  muscle-nerve  preparation,  pin 
the  lower  end  of  the  femur  to  the  cork  plate  in  the  moist  chamber, 
attach  the  thread  on  the  tendo  Achillis  to  the  lever  connected  with  the 
chamber  through  the  hole  in  the  glass  provided  for  this  purpose,  and 
arrange  the  nerve  on  the  electrodes  so  that  the  stimulating  pair  is 
between  the  muscle  and  the  polarizing  pair.  By  moving  the  secondary, 
seek  out  such  a  strength  of  stimulus  as  just  suffices  to  cause  a  weak 
tetanus  when  the  polarizing  current  is  not  closed.  Set  the  drum  off 
(slow  speed),  and  take  a  tracing  of  the  contraction.  Then  close  the 
polarizing  current  with  a  Pohl's  commutator  so  arranged  that  the 
anode  is  next  the  stimulating  electrodes — i.e.,  the  current  ascending  in 
the  nerve.  Again  open  the  short-circuiting  key  in  the  secondary;  the 
contraction  will  now  be  weaker  than  before,  or  no  contraction  at  all 
may   be  obtained.     Allow   the   preparation   two   minutes   to   recover. 


Fig.  314. — Arrangement  for  showing  Changes  of  Excitability  produced  by  the  Voltaic 
Current.  M,  muscle;  N,  nerve;  Ej,  E.^,  electrodes  connected  with  secondary 
coil  S ;  E3,  E4,  unpolarizable  electrodes  connected  with  Pohl's  commutator  (with 
cross-wires)  C;  B',  'polarizing'  battery;  B,  'stimulating'  battery  in  primary 
circuit  P;  K,  K",  simple  keys;   K',  short-circuiting  key. 

then  stimulate  again,  as  a  control,  without  closing  the  polarizing 
current.  If  the  contraction  is  of  the  same  height  as  at  first,  close  the 
polarizing  current  with  the  bridge  of  the  commutator  reversed,  so 
that  the  kathode  is  now  next  the  stimulating  electrodes.  On  stimu- 
lating, the  contraction  will  now  be  increased  in  height.  (See  Figs.  266, 
267,  p.  760.) 

9.  Pfliiger's  Formula  of  Contraction  (p.  762). — To  demonstrate  this, 
connect  two  unpolarizal^lc  electrodes,  through  a  spring  key  and  a 
commutator,  with  a  simple  rheocord  (Fig.  277.  p.  783),  so  as  to  lead 
off  a  twig  of  a  current  from  a  Daniell  cell.  The  unpolarizable  elec- 
trodes are  placed  in  a  moist  chamber.  A  muscle-nerve  preparation 
is  arranged  with  the  nerve  on  the  electrodes  and  the  muscle  attached 
to  a  lever.  The  effects  of  make  and  break  of  a  weak  current,  ascending 
and  descending,  can  be  worked  out  with  the  simple  rheocord.  The 
effects  of  a  medium  current  will  probably  be  obtained  with  a  single 
Daniell  connected  directly  with  the  electrodes  through  a  key.  The 
effects  of  a  strong  current  will  be  got  when  three  or  four  Daniells  are 
connected  with  the  electrodes.  Care  must  be  taken  to  keep  the  prepara- 
tion in  a  moist  atmosphere,  and  more  than  one  preparation  may  be 
needed  to  verify  the  whole  formula. 

52 


8i8  ELECTRO-PHYSIOLOGY 

10.  Formula  of  Contraction  for  (Human)  Nerves  in  Situ. — Connect 
eight  or  ten  dry  cells  in  series.*  Connect  one  terminal  of  the  battery 
to  a  large  plate  electrode,  and  the  other  to  a  small  electrode,  both 
covered  with  cotton,  flannel,  or  sponge,  moistened  with  salt  solutiin. 
Include  in  the  circuit  a  simple  key  for  making  or  breaking  the  current, 
and  a  commutator  for  changing  its  direction  at  will.  Leave  the  key 
open.  Place  the  large  electrode  behind  the  shoulder  (or  on  the  back 
of  the  neck),  and  the  small  electrode  over  the  ulnar  nerve  at  the  elbow 
between  the  internal  condyle  and  the  olecranon.  Arrange  the  com- 
mutator so  that  the  small  electrode  shall  be  the  kathode.  Close,  and 
then  open  the  key.  If  no  contraction  occurs  at  closing,  the  battery 
is  too  weak,  and  more  cells  must  be  added.  If  contraction  occurs  at 
closing,  but  not  at  opening,  reverse  the  commutator,  making  the  small 
electrode  the  anode,  and  observe  whether  contraction  now  occurs  at 
closing,  at  opening,  or  at  both.  Note  also  the  relative  strength  of  the 
various  contractions.  If  the  current  is  '  weak,'  the  only  contraction 
will  be  a  closing  one  when  the  kathode  is  over  the  nerve.  If  the  current 
is  of  '  medium  '  strength,  a  closing  kathodic  contraction  and  both 
opening  and  closing  anodic  contractions  will  be  obtained.  With  '  strong  ' 
currents  contractions  will  occur  at  closing  and  at  opening,  whether  the 
kathode  or  the  anode  is  over  the  nerve.  The  contractions  will  vary 
in  strength,  as  described  on  p.  763.  To  work  out  the  different  cases 
of  the  formula  summarized  in  the  table,  the  number  of  cells  must  be 
increased  or  diminished. 


Weak  Currents. 

Medium  Currents. 

Strong  Currents. 

KCC 

KCC 

ACC 
AOC 

KCC 
ACC 

AOC 
KOC 

The  abbreviations  KCC,  ACC,  are  used  respectively  for  kathodic 
closing  contraction  and  anodic  closing  contraction;  KOC,  AOC,  for 
kathodic  opening  contraction  and  anodic  opening  contraction.  KCC 
is  stronger  than  KOC,  and  ACC  than  AOC.  KCC  is  stronger  than 
ACC,  and  AOC  than  KOC.  Therefore,  as  the  strength  of  the  current 
is  increased,  in  the  case  of  normal  tissues,  KCC  is  first  obtained,  then 
ACC,  then  AOC,  and  finally  KOC. 

II.  Ritter's  Tetanus. — Lay  the  nerve  of  a  muscle-nerve  preparation 
on  a  pair  of  unpolarizable  electrodes  connected  through  a  simple  key 
with  a  battery  of  three  or  four  small  Daniells.  Connect  the  muscle 
with  a  lever.  Pass  an  ascending  current  (anode  next  the  muscle)  for 
a  few  minutes  through  the  nerve,  and  let  the  writing-point  trace  on 
a  slowly-moving  drum.  When  the  current  is  closed  there  may  be  a 
single  momentary  twitch,  or  the  muscle  may  remain  somewhat  con- 
tracted (galvanotonus)  as  long  as  the  current  is  allowed  to  pass,  or  it 
may  continue  to  contract  spasmodically  ('  closing  tetanus  ').  When 
the  current  is  opened  the  muscle  will  contract  once,  and  then  immedi- 
ately relax,  or  there  may  be  a  more  or  less  continued  tetanus  (Ritter's 
or  '  opening  tetanus  ').  If  opening  tetanus  is  obtained,  divide  the 
nerve  between  the  electrodes:  the  tetanus  continues.  Divide  it  be- 
tween the  anode  and  the  muscle:  the  tetanus  at  once  disappears.  This 
shows  that  the  seat  of  the  excitation  which  causes  the  tetanus  is  in 
the  neighbourhood  of  the  anode  (p.  804). 

*  If  the  laboratory  possesses  a  battery  (with  rheostat),  such  as  is  used  by 
neurologists,  the  experiment  is  more  conveniently  performed  with  this. 


CHAPTER  XVI 

THE  CENTRAL  NERVOUS  SYSTEM 

In  other  divisions  of  our  subject  we  have  been  able  to  follow  to  a 
greater  or  less  extent  the  processes  which  take  place  in  the  organs 
described.  The  chemistry  and  the  physics  of  these  processes  have 
bulked  more  largely  in  our  pages  than  the  anatomy  and  histology 
of  the  tissues  themselves.  In  deahng  with  the  central  nervous 
system,  we  must  adopt  a  method  the  very  reverse  of  this.  Its  ana- 
tomical arrangement  is  excessively  intricate.  The  events  which 
take  place  in  that  tangle  of  fibre,  cell,  and  fibril  are,  on  the  other 
hand,  almost  unknown.  So  that  in  the  description  of  the  physiology 
of  the  central  nervous  system  we  can  as  yet  do  little  more  than 
trace  the  paths  by  which  impulses  may  pass  between  one  portion 
of  the  system  and  another,  and  from  the  anatomical  connections 
deduce,  with  more  or  less  probability,  the  nature  of  the  physiological 
nexus  which  its  parts  form  with  each  other  and  the  rest  of  the  body. 
And  here  it  may  be  well  to  remark  that,  although  for  convenience 
of  treatment  we  have  considered  the  general  properties  of  nerves 
in  a  separate  chapter,  there  is  not  only  no  fundamental  distinction 
between  the  central  nervous  system  and  the  outrunners  which 
connect  it  with  the  periphery,  but  obviously  a  central  nervous 
system  would  be  meaningless  and  useless  without  afferent  nerves 
to  carry  information  toit  from  the  outside,  and  efferent  nerves  along 
which  its  commands  may  be  conducted  to  the  peripheral  organs. 

Section  I. — Structure  of  the  Central  Nervous  System — 
Histological  Elements. 

In  unravelling  the  complex  structure  of  the  central  nervous 
system,  we  avail  ourselves  of  information  derived  (i)  from  its  gross 
anatomy ;  (2)  from  its  microscopical  anatomy ;  (3)  from  its  develop- 
ment; (4)  from  what  we  may  call,  although  the  term  is  open  to  the 
criticism  of  cross-division,  its  phj'siological  and  pathological 
anatomy. 

Certain  tracts  of  white  or  grey  matter  arc  differentiated  from  each 
other  by  the  size  of  their  fibres  or  cells.  For  example,  the  postero- 
median column  of  the  spinal  cord   has  small    fibres,  the  direct  cere- 

819 


820  THE  CENTRAL  NERVOUS  SYSTEM 

bellar  tract  large  fibres;  the  large  pyramidal  cells  (giant  cells  or  cells 
of  Betz),  in  what  we  shall  afterwards  have  to  distinguish  as  the  '  motor 
area  '  (p.  918)  of  the  cerebral  cortex,  are  the  cells  of  origin  of  fibres  of 
the  pyramidal  tract  subserving  the  volitional  movements  of  the  limbs 
and  trunk.  The  pyramidal  cells  of  the  '  face  area  '  are  comparatively 
small.  In  general,  an  efferent  or  motor  nerve-cell  is  larger  the  longer 
its  axon  is — e.g.,  the  largest  of  all  the  pyramidal  cells  in  the  '  motor  ' 
region  are  found  in  the  portion  known  as  the  '  leg  area,'  from  which 
the  pyramidal  fibres  have  to  pass  all  the  way  down  the  cord  to  the 
segments  from  which  the  spinal  nerves  going  to  the  lower  limbs  arise. 

The  recent  work  of  Brodman  and  of  Campbell  has  shown  that  the 
cerebral  cortex  may  be  histologically  differentiated  into  regions  which 
correspond  to  a  great  extent  to  the  various  functional  regions  mapped 
out  by  physiological  methods  (p.  924). 

The  study  of  development  enables  us  not  only  to  determine  the 
homology,  the  morphological  rank,  of  the  various  parts  of  the  brain 
and  cord,  but  also,  by  comparison  of  animals  of  different  grades  of 
organization,  sometimes  to  decide  the  probable  function  and  physio- 
logical importance  of  a  strand  of  nerve-fibres  or  a  column  of  nerve- 
cells.  It  is  of  special  value  in  helping  us  to  differentiate  the  various 
areas  of  grey  matter  on  the  surface  of  the  brain,  and  to  trace  the  various 
tracts  or  paths  into  which  the  white  matter  of  the  central  nervous 
system  may  be  divided.  For  the  medullary  sheath  is  not  developed 
at  the  same  time  in  all  the  tracts,  and  a  strand  of  nerve-fibres  in  which 
it  is  wanting — e.g.,  the  pyramidal  tract  (p.  850),  which  is  the  last  of 
the  spinal  tracts  to  become  myelinated — is  readily  distinguished  under 
the  microscope. 

Then,  again — and  this  is  what  we  propose  to  include  under  the 
fourth  head — experimental  physiology  and  clinical  and  pathological 
observation  throw  light  not  only  on  the  functions,  but  also  en  the 
structure,  of  the  central  nervous  system.  For  instance,  complete  or 
partial  sectioH,  or  destruction  by  disease,  of  the  white  fibres  of  the 
cord  or  brain,  or  of  the  nerve-roots,  or  removal  of  portions  of  the  grey 
matter,  is  followed  by  degeneration  in  definite  tracts.  And  since,  as 
we  have  already  seen,  degeneration  of  a  nerve-fibre  is  caused  when  it 
is  cut  off  from  the  cell  of  which  it  is  a  process,  the  amount  and  dis- 
tribution of  such  degeneration  teaches  us  the  extent  and  position  of 
the  central  connections  of  the  given  tract.  Conversely,  the  cells  in 
which  a  tract  of  nerve-fibres  arises  may  sometimes  be  identified  by 
the  alterations  in  the  chromatin  (p.  831)  and  other  changes  which  occur 
in  them  after  section  of  their  axons.  Particularly  in  young  animals, 
removal  of  a  peripheral  organ — an  eye  or  a  limb — or  section  of  its 
nerves,  may  be  followed  by  atrophy  of  portions  of  the  central  nervous 
system  immediately  related  to  it. 

'  Softening  '  of  a  definite  portion  of  the  white  or  grey  matter  may 
also  in  certain  cases  be  caused  by  depriving  it  of  its  blood-supply  by 
the  injection  of  artificial  emboli,  and  the  resulting  degenerations  may 
then  be  studied.  For  instance,  fine  particles  like  lycopodium  spores 
are  injected  into  the  abdominal  aorta  between  the  origins  of  the  renal 
and  inferior  mesenteric  arteries.  They  are  prevented  by  clamps  from 
entering  these  vessels,  and,  passing  through  the  lumbar  arteries,  stick 
in  the  branches  of  the  anterior  spinal  artery,  and  cause  softening 
mainly  of  the  grey  matter  of  the  lumbar  portion  of  the  cord.  When 
the  abdominal  aorta  of  a  rabbit  is  temporarily  compressed  (for  about 
an  hour)  below  the  origin  of  the  renal  arteries,  the  grey  matter  of  the 
corresponding  portion  of  the  cord  is  so  seriously  injured  that  it  and 
the  fibres  that  arise  from  it  degenerate,  while  the  fibres  whose  cells  of 


DEVELOPMENT 


821 


Fu 


315.  —  Formation    of    tin.-     N'.ural 
Canal  at  an  Early  Stage  (Beard). 


origin  are  not  situated  in  this  part  of  the  grey  matter  are  not  aflfected, 
or  at  least  completely  recover. 

Certain  tracts  may  also  be  marked  out  by  means  of  the  electrical 
variation,  which  gi\-es  token  of 
the  passage  of  nervous  impulses 
along  them  when  portions  of  the 
central  nervous  system  or  peri- 
pheral nerves  are  stimulate<J 
(Horsley  and  Gotch). 

Deveiopment  of  the  Central 
Nervous  System.— Very  early  in 
development  (Fig.  315)  the  keel 
of  the  vertebrate  embryo  is  laid 
down  as  a  groove  or  gutter  in  the 
ectoderm  of  the  blastodermic  area 
(Chap.  XIX.).  The  walls  of  this 
'  medullary  '  or  '  neural  '  groove 
grow  inwards,  and  at  length  there 
is  formed,  by  their  coalescence,  the  '  neural  canal  '  (Fig.  316),  which 
expands  at  its  anterior  end  to  form  four  cerebral  vesicles  (Fig.  317). 
Thus  there  is  a  continuous  tunnel  from 
end  to  end  of  the  primary  cerebro-spinal 
axis;  and  this  persists  as  the  central 
canal  of  the  spinal  cord  and  the  ven- 
tricles of  the  brain,  whose  ciliated 
epithelium  represents  the  ectodermic 
lining  of  the  primitive  neural  canal.  In 
the  adult  portions  of  the  canal  may 
become  obliterated  from  an  overgrowth 
of  the  lining  cells,  and  the  cilia  are,  if 
present  at  aU,  less  distinct  than  in  the 
child,  and  far  less  distinct  than  in  the 
lower  animals.  From  the  wall  of  this 
canal  is  formed  the  cerebro-spinal  axis, 
in  which  developing  nerve-cells  or  neuro- 


Fig.  317. — Diagram  to  illustrate 
the  Formation  of  the  Cerebral 
Vesicles.  A.  i  indicates  the 
cavity  of  the  secondary  fore- 
brain,  which  eventually  becomes 
the  lateral  ventricles.  In  B  the 
secondary  fore-brain  has  grown 
backwards  so  as  to  overlap  the 
other  vesicles.  I,  first  cerebral 
vesicle  (primary  fore-brain  or 
'tween  brain);  II,  second  cerebral 
vesicle  (mid-brain);  III,  third 
cerebral  vesicle  (hind-brain);  IV. 
fourth  cerebral  vesicle  (after- 
brain). 


Fig.  316. — Neural  Canal  at  a  Later 
Stage  (Beard).  C,  neural  canal; 
G,  posterior  spinal  ganglion. 


blasts  soon  become  differentiated  from  the  supporting  cells  or  spongio- 
blasts, and  wander  outwards  from  the  neighbourhood  of  the  central  canal 
(Fig.  328)  till  their  further  progress  is  checked  by  the  barrier  of  the  mar- 


822  THE  CENTRAL  NERVOUS  SYSTEM 

ginal  veil,  a  closely-woven  network  or  thicket,  into  which  the  processes  of 
the  spongioblasts  break  up  at  the  outside  of  the  primitive  cerebro-spinal 
axis.  Although  the  neuroblasts  themselves  are  unable  to  penetrate 
the  marginal  veil,  the  axis-cylinder  processes  of  some  of  them  do  so, 
and  form  the  motor  roots  of  the  spinal  nerves.  The  neuroblasts  from 
which  the  fibres  of  the  white  columns  of  the  cord  are  developed  are 
apparently  unable  to  send  their  axons  through  the  marginal  veil. 
They  are  accordingly  forced  to  assume  a  longitudinal  direction,  and 
in  this  way  the  central  grey  matter  becomes  covered  with  a  sheath  of 
longitudinal  white  fibres.  For  a  time  only  motor  nerve-cells  and  the 
fibres  connected  with  them  are  developed  in  the  cerebro-spinal  axis. 
The  ganglia  on  the  posterior  roots  arise  from  a  series  of  ectodermic 
thickenings  or  sprouts  from  the  neural  crest  which  runs  along  the  dorsal 
aspect  of  the  neural  canal.  These  sprouts  contain  the  neuroblasts 
which  develop  into  the  spinal  ganglion  cells  with  the  posterior  root- 
fibres.  From  each  pole  of  each  neuroblast  a  process  grows  out,  one 
towards  the  periphery,  which  forms  a  peripheral  nerve-fibre,  the  other 
centrally  to  connect  the  cell  with  the  cord.  From  the  after-brain  (or 
myelencephalon)  is  developed  the  medulla  oblongata  or  spinal  bulb, 
from  the  hind-brain  (or  metencephalon)  the  cerebellum  and  pons, 
from  the  mid-brain  (or  mesencephalon)  the  corpora  quadrigemina  and 
crura  cerebri.  The  fore-brain,  or  primary  fore-brain  (thalamencepha- 
lon),  gives  rise  of  itself  only  to  the  third  ventricle  and  optic  thalamus; 
but  a  secondary  fore-brain  (telencephalon)  buds  off  from  it  and  soon 
divides  into  two  chambers,  from  the  roof  of  which  the  cerebral  hemi- 
spheres, and  from  the  floor  the  corpora  striata,  are  derived.  Their 
cavities  persist  as  the  lateral  ventricles,  which  communicate  with  the 
third  ventricle  by  the  foramen  of  Monro.  The  olfactory  tracts  are 
formed  as  buds  from  the  secondary  fore-brain. 

To  complete  the  story  of  the  development  of  tlie  brain,  it  may  be 
added  that  the  retina  is  really  an  expansion  of  its  nervous  substance. 
A  hollow  process,  the  optic  vesicle,  buds  out  on  each  side  from  the 
primary  fore-brain.  A  button  of  ectoderm,  which  afterwards  becomes 
the  lens,  grows  against  the  vesicle  and  indents  it  so  that  it  becomes 
cup-shaped,  the  inner  concave  surface  of  the  cup  representing  the 
retina  proper,  the  outer  convex  surface  the  choroidal  epithelium.  The 
stalk  becomes  the  optic  nerve. 

Histological  Elements  of  the  Central  Nervous  System. — The  central 
nervous  system  is  built  up  (i)  of  true  nervous  elements,  (2)  of  sup- 
porting tissue.  The  nervous  elements  have* usually  been  described  as 
consisting  of  nerve-fibres  and  nerve-cells,  but  the  antithesis  of  a  time- 
honoured  distinction  must  not  lead  us  to  forget  that  the  essential 
part  of  a  nerve-fibre,  the  axis-cylinder,  is  a  process  of  a  nerve-cell, 
and  the  medullary  sheath  a  structure  whose  integrity  is  intimately 
related  to  that  of  the  axis-cylinder.*  In  strictness,  the  term  '  nerve- 
cell  '  ought  to  include  not  only  the  cell-body,  but  all  its  processes,  out 
to  their  last  ramifications.  But  the  habit  of  speaking  of  the  position 
of  the  cell-bodyf  as  that  of  the  nerve-cell  is  so  ingrained,  that  it  seems 
better  to  continue  the  use  of  the  latter  term  in  its  old  signification,  and 
to  speak  of  the  cell  and  branches  together  as  a  neuron  (also  spelled 
neurone). 

*  While  the  medullary  sheath,  like  the  axis-cyhnder,  seems  to  be  as  regards 
its  nutrition  under  the  control  of  the  nerve-cell,  and  must  therefore  be  looked 
upon  as  an  integral  portion  of  the  neuron,  although  not  essential  for  its  de- 
velopment, the  neurilemma  in  respect  both  of  its  nutrition  and  i«ts  develop- 
ment appears  to  be  an  independent  structure. 

•f  Foster  and  Sherrington  call  the  cell-body  the  perikaryon. 


HISTOLOGICAL  ELEMENTS 


823 


The  Neurons. — A  typical  nerve-cell  (Figs.  318,  320,  322)  is  a  knot  of 
granular  protoplasm,  containing  a  large  nucleus,  inside  of  which  lies 
a  highly  refractive  nucleolus.  A  centrosome  and  attraction  sphere 
(p.  5)  have  also  been  found  in  some  nerve-cells,  though  not  as  yet 
demonstrated  in  all.  Pigment  may  also  be  present,  especially  in  old 
age.  By  certain  methods  of  staining  it  may  be  shown  that  fibrils 
(neuro-fibril.s)  run  thnnigh  the  protoplasm  of  the  cell,  forming  a  felt- 
work  in  it,  and  entering  the  dendrites  on  the  one  hand  and  the  axis- 
cylinder  process  on  the  other  (Figs.  318,  321,  325).  In  the  axis- 
cylinders  of  nerve-fibres  the  fibrils  (Fig.  319)  appear  to  preserve  their 

identity  down  to  the  distribution  of 
the  fibre.  In  the  ground  substance 
between  the  fibrils  lie  round,  an- 
gular, or  spindle-shaped  bodies 
(Nissl's  bodies)  which  stain  with 
-  "  basic  dyes  (Fig.  330).*  These  bodies 

vary    in   appearance    in    different 
,.  ,^  kinds   of  nerve-cells,   and   in   the 

same  nerve-cell  under  different  con- 

-^ ,  ditions.     According  to  Macallum. 

they  contain  organically  combined 
iron.  In  a  multipolar  cell,  like  those 


/?"/:' 


■yi^ 


Fig.  318. — Anterior  Horn  Cell  from  Man 
showing  Fibrils  (Bcthe). 


Fig.  319.  —  MeduUated  Nerve- 
Fibre  showing  Fibrils  of  .\.\is- 
Cylinder  (Bethe).  The  fibrils  are 
seen  passing,  without  interrup- 
tion, across  a  node  of  Ranvier. 


in  the  anterior  horn  of  the  spinal  cord,  several  processes — it  may  be  five 
or  six,  or  even  more — pass  off  from  the  cell-body  (Frontispiece).  The 
most  complete  pictures  of  them  are  given  by  preparations  impregnated 
according  to  the  method  of  Golgif  (Figs.  320,  323).     One  of  the  pro- 

♦  In  Nissl's  method  the  sections  are  stained  in  a  solution  of  methylene  blue, 
and  decolourized  in  anilin-alcohol. 

•f  The  method  depends  upon  the  deposition  of  mercury,  or  silver,  in  or 
around  the  cell-bodies  and  their  processes  in  tissues  which  have  been  hartlened 
in  bichromate  of  potassium  and  then  soaked  in  a  solution  of  mercuric  chloride 
or  silver  nitrate.  In  Pal's  improvement  of  Golfii's  method  a  solution  of  sodic 
sulphide  follows  the  mercuric  chloride. 


824 


THE  CENTRAL  NERVOUS  SYSTEM 


cesses  of  most  nerve-cells  is  distinguished  from  the  rest  by  the  fact 
that  it  maintains  its  original  diameter  for  a  comparatively  great 
distance  from  the  cell,  and  gives  off  comparatively  few  branches. 
This  process,  which  in  favourable  preparations  can  be  traced  on  till  it 
becomes  the  axis-cylinder  of  a  nerve-fibre,  is  called  the  axis-cylinder 
process,  or  more  shortly  the  axon.  The  few  slender  brai  ches  that  come 
off  from  it,  usually  at  right  angles,  are  called  collaterals.  The  collaterals 
consist  essentially  of  one  or  more  fibrils  of  the  axon.  Both  the  main 
thread  of  the  axon  and  the  collaterals  end  by  breaking  up  into  an 
arborescent  system  of  fibrils  or  telodendrion.  The  telodendrions  vary 
greatly  in  appearance  from  simple  end -brushes  to  far-branching 
thickets,  or  such  special  end-organs  as  motor  plates  (Fig.  325)  or 
muscular  spindles.  The  rest  of  the  processes  of  the  cell,  which  are 
termed  dendrites  or  protoplasmic  processes,  very  rapidly  diminish  in 
diameter,    as   they    pass  away   from  the  cell     by   breaking    up    into 


Fig.  320. — Multipolar  Nerve-Cell:  Golgi  Preparation  (Barker,  after  Kolliker). 
n,  axon;  c,  collaterals. 


fibrils  like  the  branches  of  a  tree.  The  Nissl  bodies  extend  for  some 
distance  into  the  dendrites,  but  not  into  the  axon.  The  dendrites 
of  some  cells,  especially  the  pyramidal  cells  of  the  cerebral,  and 
the  Purkinje's  cells  of  the  cerebellar  cortex,  have  small  swellings, 
the  so-called  lateral  buds  or  gemmtiles,  on  their  course.  Their  signifi- 
cance is  unknown.  The  dendrites  terminate  at  a  little  distance  from 
the  cell,  where  they  come  into  relation  with  the  end-arborizations  of 
the  axons  of  other  neurons.  In  this  way  two  or  more  neurons  are 
linked  together  to  form  a  nervous  path.  According  to  the  view  most 
commonly  held  (neuron  hypothesis),  the  relation  is  not  one  of  actual 
anatomical  continuity,  but  the  processes  come  so  close  together  that 
nerve  impulses  are  able  to  pass  across  from  the  terminal  brush  of  the 
axon  of  one  nervous  element  to  the  dendrites  or  cell- body  of  another. 
This  kind  of  junction  is  called  a  synapse. 

It  has  been  suggested  that  the  contact  may  be  rendered  more  or  less 
close  through  amoeboid  movements  of  the  dendrites,  ^.nd  that  in  thi?? 


HISTOLOGICAL  ELEMENTS 


825 


way  the  nervous  impulse  may  be  switched  like  a  railway-train  from 
one  path  to  another.  But  there  is  no  experimental  basis  for  this  some- 
what crude,  if  fascinating,  hypothesis.  Sherrington  has  suggested 
that  the  presence  of  a  '  membrane  '  at  the  synapse  may  limit  the  con- 
duction and  determine  its  direction.  Some  membranes,  such  as  frog's 
skin,  are  known  to  possess  a  so-called  irreciprocal  permeability  for 
certain  substances,  permitting  them  to  pass  more  easily  in  one  direc- 
tion than  the  other,  and  it  is  conceivable  that  a  membrane  at  the 
synapse  might  have  a  similar  action  in  respect  to  the  movement  of  ions 
concerned  in  the  propagation  of  the  nervous  excitation.     Whatever 


Fig.  321. — Nerve-Cells  of  Hirudo  (Schafer, 
after  Apithy).  A,  unipolar  motor  cell; 
a,  network  of  neuro-fibrils  near  the  sur- 
face of  the  cell;  6,  near  the  nucleus  n / 
c,  afferent,  d,  efferent  neuro-fibril.  B,  bi- 
polar sensory  cell  a  with  its  nucleus  n  ; 
CM,  cuticle;  ep,  epidermis  cells  between 
which  a  neuro-fibril  passes  up  from  its 
branched  ending  near  the  surface  of  the 
skin  to  the  nerve-cell,  where  it  forms  a 
network,  which  gives  off  a  fibril  passing 
towards  the  central  nervous  system. 


Fig.  322. — Large  Pyramidal  Cell  of 
Cerebral  Cortex  (Barker,  after  Bech- 
terew).     a,  axon;  b,  dendrite. 


the  nature  of  the  relation  between  two  superposed  neurons  may  be,  it 
does  not  permit  the  conduction  of  nerve-impulses  indiscriminately  in 
both  directions.  For  instance,  stimulation  of  the  central  end  of  the 
posterior  root  of  a  spinal  nerve  causes  an  electrical  response  (p.  797) 
in  the  anterior  root  of  the  same  segment,  while  no  electrical  change  is 
produced  in  the  posterior  root  by  stimulation  of  the  anterior.  We  shall 
see  later  on  (p.  844)  that  some  of  the  fibres  of  the  posterior  root  and 
their  collaterals  end  by  arborizing  arqund  the  dendrites  of  the  cells  ol 
the  anterior  horn.      Tlic  excitation  is,  therefore,  able  to  pass  from  the 


826 


THE  CEXTRAL  NERVOUS  SYSTEM 


telodendrions  of  the  posterior  root-fibres  through  the  dendrites  of  the 
anterior  horn  cells  towards  their  cell-bodies,  but  not  in  the  opposite 


Fig.  323. — a — e  shows  the  development  of  the  pyramidal  ner\'e-cells  of  the  cerebral 
cortex  in  a  t\-pical  mammal;  a,  neuroblast  with  commencing  axon;  b,  dendrites 
appearing;  d,  commencing  collaterals.  A — D  shows  the  different  degree  of  com- 
ple.xity  in  the  fully-developed  p\Tamidal  cells  in  different  vertebrates:  A,  frog; 
B,  lizard;  C,  rat;  D,  man  (Donaldson,  after  Ramon  y  Cajal). 

direction,  and  in  general  the  direction  of  conduction  is  from  the  den- 
drites towards  the  cell-body. 

Some   investigators   believe  that   the   fibrils   already   spoken   of  as 
forming  a  felt-work  in  the  protoplasm  of  the  nerve-cell  may  run  right 


Fig.  324. — Cells  from  the  Gasserian  Ganglion  of  a  Developing  Guinea-Pig.  The 
originally  bipolar  cells  are  seen  changing  into  cells  apparently  unipolar.  The 
same  process  occurs  in  the  cells  of  the  spinal  ganglia  (Van  Gehuchten). 

through  from  one  cell  to  another,  thus  constituting  an  actual  anatomical 
connection  between  the  neurons,  and  that  such  a  connection  may  be 
established  also  by  fibrils  which ^o  not  enter  the  cells  at  all,  but  run  in 
the  intercellular  substance  of  the  grey  matter.     Such  a  continuity  of 


HISTOLOGICAL  ELEMENTS 


827 


fibrils  from  cell  to  cell  has 
been  demonstrated  in  some 
of  the  invertebrates  —  e.g., 
in  annelids  (Fig.  321) — 
where  previously  the  best 
examples  of  strictly  iso- 
lated neurons  were  sup- 
posed to  be  found  (Apathy). 
The  supporters  of  the 
theory  of  continuity  look 
upon  the  cell-body  as 
merely  necessary  for  the 
nutrition  of  the  nerve-net, 
but  deny  that  it  is  neces- 
sary for  the  conduction  of 
nerve-impulses.  If  this  is 
the  case,  it  is  obvious  that 
the  neurons  can  no  longer 
be  considered  as  functional 
units  in  which  the  law  of 
isolated  conduction  of 
nerve-impulses  (p.  767) 
holds  good.  Nor  is  it  by 
any  means  so  easy  to  un- 
derstand as  on  the  neuron 
hypothesis  such  facts  as  the 
strict  limitation  of  Wal- 
lerian  degeneration  to  the 
boundaries  of  the  neurons 
directly  affected,  or  the 
strict  limitation  of  the 
silver  reduction  in  Golgi 
preparations  to  single  neu- 
rons. It  is,  of  course,  true 
that  the  simplicity  and 
order  introduced  by  the 
neuron  hypothesis  into  our 
conceptions  of  the  nervous 
conduction  paths  by  no 
means  prove  its  accuracy. 
Yet  they  are  reasons  for 
not  lightly  abandoning  it, 
and  it  has  recently  been 
corroborated  by  important 
new  evidence  on  the  growth 
of  nerve-cells  on  artificial 
media  outside  of  the  body 
(p.  776;  Fig.  327,  p.  829). 
Varieties  of  Neurons. — 
Nearly  all  the  nerve-ccUs 
of  the  cerebro-spinal  axis 
agree  with  the  cells  of  the 
anterior  horn  in  the  posses- 
sion of  an  axon  and  one  or 
more  dendrites,  although 
sometimes  the  dendrites 
are  scanty  in  number  and 


Fig.  325. — Scheme  of  Lower  Motor  Neuron 
(Barker),  a,  h,  axon-hillock  (the  portion  of  the 
cell  from  which  the  axon  comes  off),  containing 
no  Nissl  bodies,  and  showing  fibrillation;  ax. 
axis-cylinder  or  axon;  m,  medullary  sheath, 
outside  of  which  is  the  neurilemma;  c,  cell- 
substance  (cytoplasm),  showing  Nissl  bodies  in 
a  lighter  ground  substance;  d,  protoplasmic 
processes  or  dendrites  containing  Nissl  bodies; 
n,  nucleus;  n',  nucleolus;  n,  R,  node  of  Ranvier; 
s.f.  side  fibril ;  n  of  w,  nucleus  of  the  neurilemma; 
tel..  motor  end-plate;  m',  striped  muscle-fibre; 
s,  1.,  incisure. 


828 


THE  CENTRAL  NERVOUS  SYSTEJVl 


insignificant  in  size.  In  the  cerebral  cortex  the  typical  cells  are  of 
pyramidal  shape.  From  the  base  comes  oflf  the  axon,  and  from  the 
angles  dendritic  processes,  a  particularly  massive  dendrite  proceeding 
from  the  apex  of  the  pj-ramid  towards  the  surface  of  the  brain. 

Sometiines  an  axon,  instead  of  ending  in  an  arborization  which 
comes  into  relation  with  the  dendrites  of  another  nerve-cell,  or,  as  is 
more  frequently  the  case,  with  the  dendrites  of  more  than  one  cell, 
breaks  up  into  a  sort  of  basket-work  of  fibrils  surrounding  the  cell- 
body.  The  cells  of  Purkinje,  for  instance,  in  the  cerebellum  are  sur- 
i"ounded  by  such  pericellular  baskets  (Fig.  326).  The  cells  of  the  spinal 
ganglia  have  two  axons,  which  in  the  embryo  arise  one  from  each  end 
of  the  bipolar  cell,  but  in  the  adult,  in  all  vertebrates  except  some 
fishes,  are  connected  to  the  cell  by  a  single  process  (Fig.  324).  It  has 
been  commonly  held  that  the   unipolar  cell  with  a  single  T-shaped 

process  is  developed  from  a  bipolar  cell, 
which  grows  towards  one  side,  so  that  the 
two  processes  come  together  and  fuse. 
Such  observations  as  that  of  Harrison  on 
the  bifurcation  of  the  growing  end  of  the 
main  process  of  isolated  nerve-cells  culti- 
vated in  vitro  suggest  an  alternative  and 
a  simpler  explanation  —  viz.,  that  the 
T-shaped  process  is  derived  from  the 
splitting  of  a  single  chief  process.  If  this 
be  the  case,  one  of  the  original  processes 
at  the  poles  probably  undergoes  a  retarded 
development  or  disappears,  since  the  great 
majority  of  the  spinal  ganglion  cells  with 
the  T-shaped  process  appear  to  have  no 
dendrites.  Another  kind  of  cell  which 
seems  undoubtedly  to  be  of  nervous  nature 
is  the  '  granule-cell.'  Granule-cells  are 
much  smaller  than  the  nerve-cells  we  have 
been  describing.  Their  processes  are  much 
less  easily  followed,  but  all  appear  to  give 
off  an  axon  and  several  dendrites.  They 
contain  a  relatively  large  nucleus  (5  to  8  yu 
in  diameter),  with  only  a  mere  fringe  of 
cell-substance.  The  nucleus,  unlike  that 
of  a  large  nerve-cell,  stains  deeply  with 
haematoxylin.  Some  parts  of  the  grey 
matter  are  crowded  with  these  granule-cells — e.g.,  the  nuclear  layer 
of  the  cerebellum  and  the  substantia  gelatinosa,  or  substance  of 
Rolando,  which  caps  the  posterior  horn  in  the  cord.  In  other  parts 
they  are  more  thinly  scattered,  but  probably  they  are  as  widely  diffused 
as  the  large  nerve-cells  proper,  and  no  extensive  area  of  the  grey  matter 
is  wholly  without  them. 

Although  there  are  several  varieties  of  granules  (Hill),  they  all 
agree  in  this,  that  their  axons  run  a  comparatively  short  course,  and 
never,  or  rarely,  pass  beyond  the  grey  matter.  Another  kind  of  neuron 
which  is  also  confined  to  the  grey  matter,  and  is  typically  seen  in  the 
cortex  of  the  cerebrum  and  cerebellum,  presents  the  peculiarity  of  an 
axon  which  branches  into  an  intricate  network  immediately  after 
coming  off  from  the  cell  (cell  of  Golgi's  second  type).  Unlike  the  long 
axon  of  the  typical  large  nerve-cell,  the  axis-cylinder  process  of  this 
Golgi  cell  remains  unmeduUated. 

The  sympathetic  ganglion  cells  are  developed  from  immature  neuro- 


Fig.  326. — Pericellular  Baskets 
(Schafer,  after  Cajal).  Two 
cells  of  Purkinje  from  the 
cerebellum  are  seen  sur- 
rounded by  end  ramifications 
forming  a  basket-work,  b,  de- 
rived from  the  branching  of 
axons  of  small  nerve -cells  in 
the  molecular  layer;  a,  axon. 


HlbTuLOGlCAL  ELEMENTS 


829 


blasts  that  migrate,  in  the  course  of  development,  from  the  rudiments 
of  the  spinal  ganglia,  and  gathering  in  clumps  form  the  ganglia  of  the 
sympathetic  chain  (His).  They  agree  in  general  with  the  cells  of  the 
cerebro-spinal  axis  in  possessing  an  axon  and  one  or  more,  commonly 
several,  dendrites,  although  a  few  of  them  are  devoid  of  dendrites. 
The  great  majority  of  the  axons  remain  unmeduUated,  but  a  few 
acquire  a  very  fine  medullary  sheath. 

The  epithelium  lining  the  central  canal  of  the  cord  and  the  ventricles 
of  the  brain  has  also  been  considered  by  some  as  of  nervous  nature. 
The  fact  that  the  deep  ends  of  the  cells  are  continued  into  processes 
which  pierce  far  into  the  grey  substance  has  been  supposed  to  lend 
weight  to  this  opinion,  but  there  is  no  good  ground  for  it. 

Growth  of  Neurons. — The  growth  of  a  neuron  from  origin  to  com- 
pletion is  a  comparatively  slow  process  in  the  higher  animals.  Early 
in  foetal  life  (about  the  third  or  fourth  week  in  man)  certain  round 
germinal  cells  make  their  appearance  amid  the  columnar  ectodermic 
cells  surrounding  the  neural  canal.  From  their  division  are  formed, 
in  the  first  months  of  embryonic  life,  the  primitive  nerve-cells  or 
neuroblasts.     These  soon  elongate  and  push  out  processes,   first  the 


Fig.  327. — Isolated  nerve-cells  from  the  spinal  cord  of  a  tadpole  growing  in  clotted 
Ivmpli.  A,  B,  C,  are  cells  in  different  stages  of  growth.  The  lower  view  of  C 
was  drawn  under  the  microscope  4 J  hours  later  than  the  upper  (Harrison). 


axon  or  axons,  and  then  the  dendrites  (Fig.  323).  The  formation  of 
the  axons  from  the  nerve-cell  is  most  clearly  followed  in  isolated 
cultures  (Fig.  327).  As  development  goes  on,  the  cell-body  grows 
larger,  and  the  processes  longer  and  more  richly  branched.  The  axon 
and  its  collaterals,  when  it  has  any.  in  the  case  of  the  great  majority  of 
the  nervous  elements  of  the  brain  and  cord,  ultimately  acquire  a 
medullary  sheath,  although,  as  we  have  said,  the  time  at  which  medul- 
lation  is  completed  varies  in  different  groups  of  elements,  and  in  some 
nervous  tracts  it  is  even  wanting  at  birth.  At  birth,  too,  the  branches 
of  many  of  the  cells  are  less  numerous,  and  the  connections  between 
different  nervous  elements  therefore  less  intimate  than  they  will  after- 
wards become.  For  many  years  the  processes,  and  particularly  the 
axons,  continue  not  only  to  grow  longer,  but  to  grow  tliicker  as  well. 
The  cell-body  also  enlarges,  and  the  quantity  of  material  in  it  that 
stains  with  basic  dyes  increases.  In  the  growing  (lumbar)  spinal 
ganglia  of  the  white  rat  the  increase  in  volume  of  the  largest  cell- 
bodies  is  very  closely  correlated  with  tlic  increase  in  area  of  the  cross- 
section  of  the  nerve-fibres  growing  out  of  them.  The  cross-section 
of  the  axis-cylinder  is,  and  remains,  almost  exactly  equal  to  the  area 


830 


THE  CENTRAL  NERVOUS  SYSTEM 


of  the  medullary  sheath  (Donaldson).  Even  after  puberty  is  reached 
the  anatomical  organization  of  the  nervous  system  may  still  continue 
to  advance,  although  at  an  ever-slackening  rate,  and  the  finishing 
touches  may  only  be  given  to  its  architecture  in  adult  life.  In  old 
age  the  nervous  elements  decay  as  the  body  does.  The  cell- 
body  diminishes  in  size;  the  stainable  material  lessens  in  amount; 
vacuoles  form  in  the  protoplasm  and  pigment  accumulates ;  the  nucleus 
shrinks;  the  nucleolus  is  obscured  or  may  disappear  altogether.  At 
the  same  time  the  processes  of  the  cell,  and  especially  the  dendrites, 
tend  to  atrophy  (Fig.  329). 

Nutrition  of  the  Neuron. — We  have  already  seen  that  when  an  axon 
is  cut  off  from  its  cell-body,  it  and  its  medullary  sheath,  when  it 
possesses  one,  undergo  a  rapid  degeneration.     It  was  long  supposed 


Fig.  328.  —  Section 
through  Half  of  Neural 
Tube  (Barker,  after 
His).  The  pear- 
shaped  neuroblasts  are 
seen  migrating  out- 
wards. The  axons  of 
Some  of  them  are  seen 
pushing  their  way  out 
through  the  marginal 
veil  as  the  anterior 
root  of  a  spinal  nerve. 


3.^ 


Fig.  329. — 1,  spinal  gaaglion  cells  of  a  still-bom  male 
child;  2,  of  a  man  ninety-two  years  old  (  X  250) 
— N,  nuclei;  3,  nerve-cells  from  the  antennary 
ganglion  of  a  honey-bee  just  emerged  in  the  per- 
fect form;  4,  of  an  old  honey-bee.  The  nucleus  is 
black  in  the  figure.  In  3  it  is  very  large,  in  4  it 
is  shrunken  and  the  cell-substance  contains 
vacuoles  (Hodge). 


that  no  change  took  place  in  the  nerve-cell.  The  researches  of  recent 
years  have  shown  that  not  only  does  loss  of  the  specific  function  and 
trophic  influence  of  the  cell-body  affect  the  nutrition  of  the  axon,  but 
loss  of  function  of  the  axon  reacts  on  the  cell-body.  In  many  cases 
at  least,  when  a  nerve-fibre  is  divided  from  its  cell,  characteristic 
changes  are  produced  in  the  latter  and  in  its  dendritic  processes,  and 
they  are  scarcely  less  rapid,  although  usually  less  profound,  and  far 
more  transient  than  the  degeneration  in  the  peripheral  portion  of  the 
nerve-fibre.  The  cell-body  and  the  nucleus  swell.  Many  of  the  Nissl 
bodies  (Fig.  330)  disintegrate,  and  arc  reduced  to  a  finely  granular 
condition.  After  a  time  much  of  the  disintegrated  chromatic  sub- 
stance disappears  altogether.     The  nucleus  may  be  displaced  to  one. 


HISTOLOGICAL  ELEMENTS 


831 


side  of  the  cell.  Certain  changes  in  the  neurofibrils  of  the  cell  may 
accompany  the  changes  in  the  chromatin.  In  rabbits  after  division 
of  the  facial  nerve  the  alterations  in  its  nucleus  of  origin  have  been 
found  to  reach  a  maximum  in  about  three  weeks,  after  which  there  is  a 
tendency  to  recovery  on  the  part  of  the  majority  of  the  cells,  even  when 
regeneration  of  the  nerve  has  been  prevented  by  cutting  out  a  portion 
of  it.  Some  of  the  cells  may  completely  atrophy  and  disappear. 
Similar  changes  have  been  found  by  Warrington  in  the  motor  cells  ol 
the  anterior  horn  after  section  of  the  posterior  (dorsal)  spinal  roots. 
Since  in  this  case  no  anatomical  injury  has  been  inflicted  on  the  motor 
neurons,  it  has  been  surmised  that  the  cause  of  the  alterations  is  the 
loss  of  impulses  which  normally  reach  them  along  their  dendrites.  In 
short,  we  may  say,  with  Marinesco,  that  the  functional  and  anatomical 
integrity  of  the  neuron  depends  on  the  integrity  of  all  its  constituent 
parts,  and  of  the  neurons  which  carry  to  it  functional  excitations — i.e., 
excitations  connected  with  its  proper  physiological  work.  The  neuron, 
in  fact,  lives  by  its  function,  or,  in  common  language,  by  doing  its 
work.     Yet  the  anatomical  tokens  of  mere  disuse,  as  in  the  motor  cells 


Fig.  330. — Cells  from  the  Nuclei  of  the  Oculo-Motor  Nerves  of  the  Cat  Thirteen  Days 
after  Division  of  the  Root-Fibres  on  one  Side:  Nissl's  Stain  (Barker,  after  Flatau). 
a,  normal  cell  from  side  on  which  the  roots  were  not  cut ;  b,  cell  from  side  operated 
upon.  Only  a  few  Nissl  bodies  are  present  in  b,  and  the  nucleus  is  displaced  to 
one  side  of  the  cell. 


of  the  anterior  horn  after  division  of  the  cord  at  a  higher  level,  are  less 
distinct  than  those  which  follow  section  of  the  axon.  Therefore  it 
must  be  concluded  that  the  latter,  although  not  indispensable  for  the 
nutrition  of  the  cell  as  the  cell  is  for  the  axon,  exerts  an  influence  upon 
it.  Similar  changes  in  the  chromatin  may  also  be  produced  in  nerve- 
cells  by  a  period  of  anaemia,  in  extensive  superficial  burns,  in  tetanus 
caused  by  the  injection  of  bacterial  cultures,  in  acute  alcoholic  poisoning, 
in  fatigue,  and  in  other  ways.  According  to  Wright,  the  inhalation 
of  ether  or  chloroform  (in  dogs)  so  alters  the  chromatic  substance 
that  it  loses  its  affinity  for  aniline  dyes.  In  long-continued  anaesthesia 
the  nucleus  is  also  affected,  while  the  nucleolus  is  the  last  part  of  the 
cell  to  suffer.  A  greater  alteration  occurs  in  the  cells  in  the  three  hours 
between  the  sixth  and  ninth  hours  of  anaesthesia  than  in  the  five  hours 
between  the  first  and  sixth.  Although  the  changes  are  tran<;itory,  the 
cells,  after  a  narcosis  of  nine  hours,  being  practically  normal  in  forty- 
eight  hours,  they  indicate  that  the  duration  of  safe  surgical  anaesthesia 
has  a  limit  measured  by  hours. 

It  is  prob  ble  that  the  alterations  in  the  chromatic  substance  should 


8,32 


THE  CENTRAL  NERVOUS  SYSTEM 


not  be  looked  upon  as  the  token  of  any  specific  lesion;  they  are  the 
common  structural  response  of  the  cell  to  injurious  influences  of  the 
most  varied  nature. 

Grey  and  White  Matter. — Nerve-cells  are  the  most  distinctive  his- 
tological feature  of  the  grey  nervous  substance.  Sown  thickly  in  the 
cerebral  cortex,  the  basal  ganglia,  the  floor  of  the  fourth  ventricle,  and 
the  cervical  and  lumbar  enlargements  of  the  cord,  they  are  scattered 
more  sparingly  wherever  the  grey  matter  extends.  They  also  occur 
in  the  spinal  ganglia,  and  their  cerebral  homologues  (such  as  the  Gas- 
serian  ganglion),  in  the  ganglia  of  the  sympathetic  system,  and  the 
sporadic  ganglia  in  general.  But  wide  as  is  their  distribution,  and 
great  as  is  the  size  of  the  individual  cells,  some  of  which  have  a  diameter 
of  140/i,  or  even  more,  they  yet  make  up  but  a  small  portion  of  the  whole 
of  the  central  nervous  substance,  the  total  weight  of  the  9,000  millions  of 
nerve-cell  bodies  in  the  human  brain  being  less  than  27  grammes 
(Donaldson).  And  although  it  is  not  to  be  wondered  at  that  objects 
so  notable  when  viewed  under  the  microscope  should  have  struck  the 

imagination  of  physiologists,  it  is  probable 
that  the  very  high  powers  which  it  is  so 
common  to  attribute  exclusively  to  them 
are,  in  part  at  least,  shared  with  the  network 
or  feltwork  formed  by  their  processes. 

The  grey  matter,  in  addition  to  this  ex- 
ceeding!}'delicate  feltwork  of  non-medullated 
fibres  and  filaments  representing  the  den- 
drites and  such  axons  and  collaterals  as 
terminate  within  itself,  contains  also,  as  may 
be  seen  in  preparations  stained  by  Weigert's 
method,*  great  numbers  of  exceedingly  fine 
medullated  fibres,  many  of  which  are  the 
collaterals  of  fibres  that  are  passing  out  to  the 
white  matter. 

Only  medullated  nerve-fibres  are  met  with 
in  the  white  matter  of  the  cerebro-spinal  axis. 
They  are  commonly  stated  to  be  devoid  of  a 
neurilemma  (or  neurolemma) ,  and  in  the  sense 
that  there  is  no  continuous  separate  mem- 
branous sheath  corresponding  to  the  sheath 
of  Schwann  of  the  peripheral  medullated 
fibres  this  is  correct.  Sheath  cells,  however, 
are  present,  and  form  a  reticulum  around  each  fibre  in  the  meshes 
of  which  myelin  is  contained.  In  diameter  the  medullated  fibres  of 
the  white  matter  vary  from  2  /i  to  20  /j,.  In  Malapterurus  electricus 
the  fibre  in  the  cord  which  supplies  the  electrical  organ  is  of  immense 
size;  and  in  the  anterior  column  of  many  fishes  may  also  be  seen  a 
single  gigantic  fibre  on  each  side  with  a  diameter  of  nearly  100  /x.  It 
cannot  be  said  that  any  relation  between  the  functions  of  neurons 
and  the  calibre  of  their  axons  has  been  definitely  established.  Many 
afferent  fibres,  it  is  true,  are  small — this  is  notably  the  case  with  the 
fibres  of  the  posterior  column,  and  many  motor  fibres  are  large.  But 
the  distinction  can  by  no  means  be  generalized,  for  the  fibres  of  the 
direct  cerebellar  tract  (p.  838),  which  certainly  are  afferent,  are  amongst 
the  largest  in  the  spinal  cord ;  and  the  vaso-motor  fibres,  which  pass  from 
the  cord  by  the  anterior  (ventral)  roots  (Fig.  331)  into  the  sympathetic, 
are  smaller  than  the  fibres  of  the  posterior  column.     Even  the  motor 

*  Weigert's  is  a  special  method  of  staining  the  medullary  sheatii  with 
haematoxylin. 


Fig.  331. — Transverse  Section 
of  a  Bundle  of  Nerve- 
Fibres  from  the  Anterior 
(Ventral)  Root  of  the  First 
Coccygeal  Nerve  of  the  Cat 
(Dale).  The  great  differ- 
ence in  the  diameter  of  the 
fibres  is  well  shown.  The 
small  fibres  are  vaso-motor. 


HISTOLOGICAL  LLEMENTS  833 

nerve-fibres  of  striated  muscles  vary  considerably  in  diameter,  those  of 
the  tongue,  e.g.,  being  smaller  than  those  of  the  muscles  of  the  limbs. 
Further,  the  mcdullated  fibres  of  the  brain  are,  without  reference  to 
function,  in  general  finer  than  the  fibres  of  the  cord.  As  a  rule  the 
fibres  whose  course  is  the  longest  arc  the  thickest,  but  the  rule  is  often 
broken.  For  example,  the  average  diameter  of  the  fibres  going  to  the 
thigh  of  the  frog  is  greater  than  that  of  the  fibres  going  to  the  lower 
part  of  the  limb  (Dunn).  The  cause  of  these  differences  in  the  size  of 
nerve-fibres  is  quite  unknown.  It  is  more  likely  to  be  morphological 
than  ph^-siological. 

Supporting  Tissue. — The  protective  membranes  of  the  central  nervous 
system  consist  of  ordinary  connective  tissue  derived  from  the  meso- 
derm. The  supporting  framework  which  interpenetrates  the  nervous 
substance  consists  of  a  peculiar  form  of  tissue  derived  from  the  ecto- 
derm, and  called  neuroglia.  The  whole  cerebro-spinal  axis  is  wrapped 
in  four  concentric  sheaths.  Next  the  walls  of  the  bony  hollow  in  which 
it  lies  is  the  dura  mater.  Next  the  nervous  substance  itself,  following 
the  convolutions  of  the  brain  and  the  fissures  of  the  cord,  and  giving 
off  bloodvessels  to  both,  is  the  pia  mater.  Between  the  dura  and 
the  pia,  separated  from  the  latter  by  a  jacket  of  cerebro-spinal  fluid, 
is  the  double  layer  of  the  arachnoid.  The  comparatively  coarse  septa 
that  run  into  the  nervous  substance  as  if  coming  off  from  the  pia  mater 
are  the  main  beams  in  the  scaffolding  of  non-nervous  material  with 
which  that  substance  is  interwoven,  and  by  which  it  is  supported. 
The  interstices  are  filled  in  by  a  thick-set  feltwork  of  interlacing  neurog- 
lia fibres,  which  lie  close  against  the  small  glia  cells.  In  preparations 
impregnated  by  the  Golgi  method  many  of  the  neuroglia  fibres  appear 
to  be  processes  running  out  from  the  attenuated  cell-body  like  the 
arms  of  a  microscopic  crab  or  spider.  But  this  is  a  deceptive  appear- 
ance, as  has  been  shown  by  means  of  special  methods  in  which  the 
neuroglia  fibres  are  alone  stained  (Weigert,  Huber,  etc.).  They 
generally  lie  in  close  contact  with,  or  embedded  in,  the  protoplasm 
of  the  neuroglia  cells,  from  which  they  have  become  differentiated 
structurally  and  chemically,  but  sometimes  they  may  detach  themselv^es 
entirely  from  the  cells  and  lie  free  in  the  intervening  tissue.  The 
neuroglia  is  present  in  greatest  abundance  in  the  grey  matter  immedi- 
ately surrounding  the  central  canal  of  the  cord  and  the  ventricles  of 
the  brain  (the  ependyma,  as  it  is  called),  from  which  long  neuroglia 
fibres  pass  out  radially,  giving  off  branches  on  their  course,  and  ending 
in  little  knobs  or  enlargements  attached  to  the  pia  mater. 


Section  II.— General  Arrangement  of  the  Grey  and  White 
Matter  in  the  Central  Nervous  System. 

(i)  Around  the  central  canal,  as  we  have  seen,  a  tube  of  grey 
matter  sheathed  with  white  fibres  is  developed.  This  tube,  from 
optic  thalamus  to  conus  medullaris,  may  be  conveniently  referred  to 
as  the  central  grey  axis  or  stem,  which,  in  the  lowest  vertebrates — e.g., 
fishes — is  much  the  most  ini})ortant  part  of  the  central  nervous 
system. 

(2)  On  the  outer  surface  of  the  anterior  portion  of  the  neural 
axis,  but  not  in  the  part  corresponding  to  the  spinal  cord,  is  laid 
down  a  second  sheet  or  mantle  of  cortical  grey  matter.     Between 

53 


834  ^^^  CENTRAL  NERVOUS  SYSTEM 

tliis  and  the  primitive  grey  stem  are  interposed  {a)  the  sheath  of 
white  fibres  that  clothes  the  latter,  and  connects  its  various  parts, 
and  {b)  a  new  development  of  white  matter  (corona  radiata,  cere- 
bellar peduncles),  which  serves  to  bring  the  cortex  into  relation 
with  the  primitive  axis,  and  through  it  with  the  rest  of  the  body. 

Although  there  are  histological  and  developmental  differences 
between  the  cerebral  and  the  cerebellar  cortex,  we  may,  for  some 
purposes,  classify  them  together  as  cortical  formations.  And  we 
may  also  include  under  this  head  the  corpora  striata,  which,  although 
for  descriptive  purposes  generally  grouped  with  the  optic  thalami 
and  the  other  clumps  of  grey  matter  at  the  base  of  the  brain,  as  the 
basal  ganglia,  are  to  be  regarded  as  cortical  in  character.  As  we 
mount  in  the  vertebrate  scale  the  cortex  formation  of  the  secondary 
fore-brain  and  hind-brain  acquires  prominence. 

In  other  words,  the  grey  matter  developed  in  the  roof  of  the  cerebral 
vesicles  I.  and  III.  (Fig.  317)  (the  grey  matter  of  the  cerebral  and  cere- 
bellar cortex)  comes  to  overshadow  the  superficial  grey  matter  hitherto 
present  only  in  the  roof  of  vesicle  II.  (in  the  corpora  bigemina).  And 
this  cortex  formation  becomes  larger  in  amount,  and,  in  the  case  of 
the  cerebral  grey  matter,  more  richly  convoluted,  the  higher  we  ascend, 
until  it  reaches  its  culmination  in  man.  As  the  anterior  cerebral 
vesicles  develop,  they  spread  continually  backward,  until  at  length  the 
cerebral  hemispheres  cover  over,  and  almost  completely  surround,  the 
primary  fore-brain  and  the  mid-  and  hind-brains,  so  that  the  anterior 
portion  of  the  primitive  stem  comes,  as  it  were,  to  be  invaginated  into 
the  second  wider  tube  of  cortical  grey  matter.  This  development  of 
the  cortical  grey  substance  is  accompanied  with  a  corresponding 
development  of  nerve-fibres,  for  an  isolated  nerve-cell  (apart,  of  course, 
from  possible  embryonic  rudiments  which  have  not  undergone  com- 
plete development)  is  no  more  conceivable  than  a  railwaj'-station  the 
track  from  which  leads  nowhere  in  particular,  or  a  harbour  on  the  top 
of  a  hill. 

But  it  is  to  be  particularly  observed  that  the  new  formation  does 
not  supplant  the  old,  but  works  through  and  directs  it.  The  neuro- 
blasts of  the  cortex  do  not  throw  out  their  axons  to  make  direct  junc- 
tion with  muscles  and  sensory  surfaces.  Such  junction  the  cortex 
finds  already  established  between  the  primitive  cerebro-spinal  axis  and 
the  periphery.  It  joints  itself  on  by  nerve-fibres  to  the  cells  of  the 
central  stem;  and  we  have  reason  to  believe  that  no  single  axon  in  an 
ordinary  spinal  or  cranial  nerve*  runs  all  the  way  from  the  periphery 
to  the  cortex,  and  no  axon  of  a  cortical  nerve-cell  all  the  way  from  the 
cortex  to  the  periphery,  but  that  the  connection  is  made  by  a  chain 
of  at  least  two  neurons,  the  cell-body  of  one  of  which  is  situate  in  this 
primitive  grey  tube. 

The  fibres  from  the  cortex  of  each  cerebral  hemisphere  (corona 
radiata),  radiating  out  like  a  fan  below  the  grey  matter,  are  gathered 
together  into  a  compact  leash  as  they  sweep  down  through  the  isthmus 
of  the  brain  in  the  internal  capsule,  to  join  the  crura  cerebri.  The 
cortex  of  each  cerebellar  hemisphere,  and  the  ribbed  pouch  of  grey 

*  The  olfactory  and  possibly  to  some  extent  the  optic  nerves  are  exceptions 
to  this  statement.  Their  relation  to  the  cortex,  as  is  easily  understood  from 
the  manner  of  their  development  (p.  822),  is  different  from  that  of  the  other 
nerves 


GREY  AND  WHITE  MATTER  IN  THE  SPINAL  CORD       835 

matter,  known  as  the  corpus  dentatum,  which  is  buried  in  its  white 
core,  are  also  connected  by  strands  of  fibres  with  tlic  central  stem  and 
the  cerebral  mantle.  The  rcstiform  body  or  inferior  peduncle  brings 
the  cerebellum  into  communii  ation  with  the  spinal  cord.  The  superior 
peduncle  by  one  path,  and  the  middle  peduncle  by  another,  connect  it 
with  the  cerebral  cortex.  A  great  transverse  commissure,  the  corpus 
callosum,  unites  the  cerebral  hemispheres  across  the  middle  line,  while 
transverse  fibres,  that  break  through  the  middle  lobe  or  worm,  form 
a  similar  though  far  less  massive  junction  between  the  two  hemispheres 
of  the  cerebellum. 

The  fibres  of  the  nervous  system  may  be  divided  into  (i)  fibres 
connecting  the  peripheral  organs  with  nerve-cells  in  the  central  grey 
axis;  (2)  fibres  connecting  nerve-cells  in  this  central  axis  with  cells 
in  the  external  or  cortical  grey  tube;  and  (3)  fibres  linking  cortex 
with  cortex,  or  central  ganglia  with  each  other.  In  the  third  group 
are  included  [a)  fibres  which  connect  portions  of  the  cortex  on  the 
same  side  (association  fibres) ;  (b)  fibres  which  connect  portions  on 
opposite  sides  of  the  middle  line  (commissural  fibres) ;  (c)  fibres  which 
connect  the  central  grey  matter  at  different  levels — e.g.,  the  proprio- 
spinal  or  endogenous  fibres  of  the  cord.  Our  first  task  is,  therefore, 
to  trace  the  peripheral  nerves  to  their  cells  of  origin  or  centres  of 
reception*  in  the  nervous  stem.  And  although  there  is  reason  to 
believe  that  the  whole  of  the  peripheral  nerves,  cerebral  and  spinal 
(with  the  exception  of  the  olfactory  and  optic,  which  are  rather 
portions  of  the  brain  than  true  peripheral  nerves),  form  a  morpho- 
logical series,  it  will  be  well  to  begin  with  the  spinal  nerves,  since 
their  motor  and  sensory  fibres  are  gathered  into  different  and  definite 
roots,  whose  course  within  the  cord  is,  in  general,  more  easily  traced 
than  the  course  of  the  cerebral  root-bundles  within  the  brain. 

Section  III. — ^Arrangement  of  the  Grey  and  White  Matter 
IN  the  Spinal  Cord. 

The  grey  matter  of  the  spinal  cord  is  arranged  on  each  side  in  a 
great  unbroken  column  of  roughly  cresccntic  section,  joined  with 
its  fellow  across  the  middle  line  by  a  grey,  bar  or  bridge,  which 
springs  from  the  convexity  of  the  crescent,  and  is  pierced  from  end 
to  end  by  the  central  canal.  The  anterior  horn  of  the  crescent, 
although  it  varies  in  shape  at  different  levels  of  the  cord,  is,  in 
general,  broad  and  massive,  in  comparison  with  the  slender  and 
tapering  posterior  horn.  In  the  lower  cervical  and  upper  dorsal 
region  a  moulding  or  projection,  forming  a  lateral  horn,  springs 
from  the  fluted  outer  side  of  the  grey  substance.  Within  the  grey 
matter  nerve-cells  are  found,  sometimes  so  regularly  arranged  that 
they  form  veritable  cellular  or  vesicular  strands.     Of  these  the  best 

♦  The  centre  or  nucleus  of  reception  of  a  nerve  contains  the  nerve-cells 
around  which  its  axons  terminate;  the  nucleus  of  origin  of  a  nerve  contains 
the  cells  from  which  its  axons  arise. 


836 


THE  CENTRAL  NERVOUS  SYSTEM 


marked  are— (i)  The  tract  or  tracts  made  up  by  the  cells  of  the 
anterior  horn  (Fig.  332),  which  practically  run  from  end  to  end  of  the 
cord,  swell  out  in  the  cervical  and  lumbar  enlargements,  where  the 
cells  are  very  numerous  and  of  great  size  (70  /n  to  140  /n  in  diameter), 
and  contract  to  a  thin  thread  in  the  thoracic  region,  where  they  are 
relatively  few,  scattered,  and  small.  In  the  enlargements  there 
are  several  groups  of  these  cells  corresponding  with  the  segments 

of  the  limbs,  the  movements 
of  the  hand,  forearm,  and 
upper  arm  being  each  repre- 
sented by  a  group  in  the 
cervical,  and  those  of  the  foot, 
leg,  and  thigh  by  groups  in 
the  lumbar  swelling.  In  the 
rest  of  the  cord  only  two 
well-marked  groups  of  cells 
are  present  in  the  anterior 
horn,  a  mesial  and  a  lateral. 
(2)  Clarke's  column,  whose 
cells,  mostly  of  good  size  and 
somewhat  rounded  in  outline, 
are  situated  at  the  inner  side 
of  the  root  of  the  posterior 
horn  just  where  it  joins  on  to 
the  grey  cross-bar.  It  gradu- 
ally increases  in  size  from 
above  downwards,  usually 
appearing  first  at  the  level  of 
the  seventh  or  eighth  cervical 
nerve,  attaining  its  maximum 
development  at  the  eleventh 
or  twelfth  dorsal  and  dis- 
appearing altogether,  as  a 
continuous  strand,  at  the  level 
of  the  second  or  third  lumbar 
nerves.  Scattered  nerve-cells, 
however,  constituting  the  so- 
called  cervical  and  sacral  nuclei  of  Stilling,  are  frequently  found 
occupying  the  same  position  towards  the  upper  and  lower  ends  of 
the  cord,  and  may  be  looked  upon  as  isolated  portions  of  Clarke's 
column.  (3)  A  tract  of  small  cells  called  the  intermedio-lateral 
tract,  lateral  cell  column,  or  lateral  horn,  situated  at  the  outer  edge 
of  the  grey  matter,  about  midway  between  the  anterior  and  pos- 
terior horns.  It  is  best  marked  in  the  thoracic  region,  up  to  about 
the  second  thoracic  segment,  although  in  the  corresponding  situa- 
tion there  are  scattered  cells  in  the  lumbar  swelling  and  the  cervical 


Siillings  Cervical 
'nucleus 
CeruLCoi 
Lnlargemevt 


Idteml  CsJl-cohimrx 
Ccolumn  Of- 1he  inter- 
niedio-iaCeral  tract) 

Stillinp's  dorsal 

nucleus  orChrk&5 
Column 

Cells  oi  1he,  anhriot 
Cornu 


Scattered  cells  erf 
intermedio-lcitwaf 
tract 
lumhdrErjlar^merit 

StiUinQS  'Sacral 
nu.e2&u3 


Fig.  332. — Diagram  of  Grey  Tracts  of  Cord. 


GREY  AND  WHITE  MATTER  IN  THE  SPINAL  CORD        837 

cord.  There  is  reason  to  believe  that  the  axons  of  cells  of  the  inter- 
medio-lateral  tract,  which  pass  out  as  small  medullated  fibres  in 
the  anterior  roots,  form  the  preganglionic  segments  of  the  efferent 
vascular  and  visceral  nerves  (p.  183).  (4)  The  cells  of  the  posterior 
horn,  which,  although  numerous,  are  smaller  than  those  of  the 
anterior  horn.  Throughout  the  whole  cord,  however,  two  small 
groups  of  cells  may  be  distinguished,  one  on  the  lateral  side  of  the 
horn,  about  its  middle,  and  the  other  on  the  mesial  side,  a  little 
in  front  of — i.e.,  ventral  to — the  edges  of  the  substance  of  Rolando. 
Both  of  these  groups  are  broken  up  by  the  passage  through  them 
of  bundles  of  fibres  which  form  a  network,  and  they  are  therefore 
called  respectively  the  group  of  the  lateral  and  the  group  of  the 
posterior  reticular  formation. 

The  white  matter  of  the  cord  is  anatomically  divided  by  the 
position  of  the  nerve-roots  and  the  anterior  and  posterior  fissures 


Fig.  333. — Diagrammatic  Section  of  the  Spinal  Cord  in  the  Cervical  and  Lumbar 
Enlargements,  to  show  Tracts  of  Fibres  (Starr),  i,  antero-median  colmnn; 
2,  antero-lateral  column;  3,  ascending  antero-lateral  or  Gowers'  tract;  4,  mar- 
ginal tract  (ground  bundle,  consisting  of  short  endogenous  fibres);  5,  lateral  or 
crossed  p>Tamidal  tract;  6,  direct  cerebellar  tract;  7,  tract  of  Lissauer;  8,  ex- 
ternal portion,  and  9,  root  zone,  of  Burdach's  column;  10,  comma  tract;  11,  pos- 
terior commissural  tract;  12,  Goll's  column;  13,  septo-marginal  tract. 

into  three  columns  on  each  side:  the  anterior,  lateral,  and  posterior 
columns.  The  first  two,  since  they  are  not  separated  by  a  perfectly 
definite  boundary,  are  often  grouped  together  as  the  antero-lateral 
column.  In  the  cervical  region  it  may  be  seen  with  the  microscope 
that  the  posterior  white  column  is  almost  bisected  by  a  septum 
running  in  from  the  pia  mater  towards  the  grey  commissure.  The 
inner  half  is  called  the  postero-median  column,  or  column  of  GoU; 
the  outer  half  the  postero-external  column,  or  column  of  Burdach 
(Fig.  333)-  No  localization  of  any  of  the  other  conducting  paths 
in  the  cord  is  possible  by  gross  anatomical  examination;  but  by 
means  of  the  developmental  method  and  the  method  of  degenera- 
tion the  columns  of  Goll  and  Burdach  can  be  followed  throughout 
the  cord,  and  several  similar  areas  can  be  mapped  out.  We  shall 
only  mention  those  that  are  physiologically  the  most  important. 


838  THE  CENTRAL  NERVOUS  SYSTEM 

When  the  spinal  cord  is  divided,  and  the  animal  allowed  to  survive 
for  a  time,  certain  tracts  are  picked  out  by  the  degeneration  of  their 
fibres,  although  in  every  degenerated  tract  some  fibres  remam  un- 
affected. We  may  distinguish  the  tracts  that  degenerate  above 
the  lesion  (ascending  degeneration)  from  those  that  degenerate 
below  the  lesion  (descending  degeneration). 

Ascending  Tracts. — ^Above  the  lesion  degeneration  is  found  both 
in  the  posterior  and  the  antero-lateral  columns.  Immediately 
above  the  section  nearly  the  whole  of  the  posterior  column  is  in- 
volved. Higher  up  the  degeneration  clears  away  from  Burdach's 
tract,  and,  shifting  inwards,  comes  to  occupy  a  position  in  the 
column  of  Goll.  In  the  antero-lateral  column  two  degenerated 
regions  are  seen,  both  at  the  surface  of  the  cord,  one  a  compact, 
sickle-shaped  area  extending  forwards  from  the  neighbourhood  of 
the  line  of  entrance  of  the  posterior  roots,  and  the  other  an  area  of 
scattered  degeneration,  embracing  many  intact  fibres,  and  complet- 
ing the  outer  boundary  of  the  column  almost  to  the  anterior  median 
fissure.  The  compact  area  is  called  the  dorsal  or  direct  cerebellar 
tract,  or  tract  of  Flechsig  (or  the  fasciculus  cerehello-spinalis) ,  the  diffuse 
area  the  antero-lateral  ascending  tract,  or  tract  of  Gowers,  or  ventral 
cerebellar  tract  (or  the  fasciculus  antero-lateralis  superficialis).*  The 
dorsal  cerebellar  tract  is  distinguished  by  the  large  size  of  its  fibres. 
It  is  only  distinct  in  the  dorsal  and  cervical  regions  of  the  cord.  The 
tract  of  Lissauer,  or  posterior  marginal  zone,  is  another  small  ascend- 
ing tract  at  the  outer  side  of  the  tip  of  the  posterior  horn.  It  is 
made  up  of  fine  fibres  from  the  posterior  roots  which  soon  pass  into 
the  posterior  column. 

Descending  Tracts. — When  the  cord  is  divided,  say,  in  the  upper 
dorsal  or  cervical  region,  the  following  tracts  degenerate  below  the 
lesion : 

(i)  A  small  group  of  fibres  close  to  the  antero-median  fissure, 
which  has  received  the  name  of  the  direct  pyramidal  tract — pyramidal 
because  higher  up  in  the  medulla  oblongata  it  forms  part  of  the 
pyramid ;  direct,  because  it  does  not  cross  over  at  the  decussation  of 
the  pyramids,  but  continues  down  on  the  same  side.  In  the  stan- 
dard anatomical  nomenclature  it  is  termed  the  fasciculus  cerebro- 
spinalis  anterior.  The  direct  pyramidal  tract  is  only  present  in  man 
and  the  higher  apes. 

(2)  A  tract  of  degenerated  fibres  in  the  posterior  part  of  the 
lateral  column.  This  is  the  lateral  or  crossed  pyramidal  tract  (or  the 
fasciculus  cerebro-spinalis  lateralis) ,  and  is  much  larger  than  the  direct. 
In  the  medulla  it  also  lies  within  the  pyramid,  but,  unlike  the  direct 
pyramidal  tract,  it  crosses  to  the  opposite  side  of  the  cord  at  the 
decussation.  The  pyramidal  tracts  are  also  called  corticospinal  to 
indicate  their  origin  and  termination. 

*  Some  writers  employ  the  terms  dorsal  and  ventral  s/>mo- cerebellar 
tracts. 


GREY  AND  WHITE  MATTER  IN  THE  SPINAL  CORD        839 


(3)  A  tract  of  sc.itlerod  degeneration  l3inp^  along  the  margin  of  the 
cord  in  the  anterior  portion  of  the  antero-lateral  column,  and  partly 
overlapping  the  tract  of  Gowers.  It  is  called  the  antero-lateral 
descending  tract,  or  tract  of  Loewenthal,  or  the  vestibulospinal  tract. 

(4)  The  prepyramidal  (or  rubrospinal)  tract,  or  Monakorv's  tract 
(also  called  the  fasciculus  intermedio-latcralis),  lying  immediately  in 
front  of  the  crossed  pjTamidal  tract. 

(5)  A  small,  comma-shaped  island  of  degeneration  (comma  tract) 
can  be  followed  downwards  for  a  short  distance  in  the  middle  of 
Burdach's  column.    It  is  only 


and 


DC 


D.P 


V.B 


seen    in    the    cervical 
upper  thoracic  regions. 

Less  well  Icnown  descending 
tracts  are — 

(6)  The  olive  -  spinal  and 
thalamico  -  spinal  tracts  (or 
Helweg's  bundle)  in  the  antero- 
lateral column  opposite  the 
head  of  the  anterior  horn. 
This  tract  does  not  pass  down 
beyond  the  lower  cervical  re- 
gion. The  olivo-spinal  tract 
appears  to  consist  of  fibres 
running  down  from  the  olivary 
body  into  the  cord,  while  the 
thalamico-spinal  tract  is  made 
up  of  descending  fibres  origina- 
ting in  the  optic  thalamus. 
This  is  an  important  tract  in 
the  lower  vertebrates,  but  not 
in  man. 

(7)  The  tract  of  Marie  in  the 
anterior  column  is  chiefly  a 
continuation  into  the  cord  of 
the  posterior  longitudinal  bundle,  one  of  the  conspicuous  tracts  of  the 
brain-stem  or  upper  portion  of  the  cercbro-spinal  axis  (p.  857).  It 
contains  both  ascending  and  descending  fibres. 

When  we  have  deducted  the  long  ascending  and  descending  tracts 
which  have  been  described,  there  still  remains  in  the  antero-lateral 
column  a  balance  of  white  matter  unaccounted  for.  This  white 
substance,  which  does  not  degenerate  for  any  great  distance  either 
above  or  below  a  lesion,  is  called  the  antero-lateral  ground-bundle, 
and  lies  chiefly  in  the  form  of  an  incomplete  ring  around  the  grey 
matter.  For  descriptive  purposes  it  is  sometimes  distinguished  as 
the  anterior  ground-bundle  (or  fasciculus  anterior  proprius)  in  the 
anterior  column,  and  the  lateral  ground-bundle  (or  fasciculus  lateralis 
propritcs)  in  the  lateral  column.  It  is  believed  to  consist  of  fibres 
(endogenous  or  proprio-spinal  fibres)  which  run  only  a  comparatively 
short  course  in  the  cord,  and  serve  to  connect  nerve-cells  at  different 
levels.     Some   of  these  endogenous   fibres  are  ascending,   others 


Fig.  334. — Scheme  of  Cross-Section  of  Spinal 
Cord  (Donaldson,  after  Lenhossek).  On  the 
left  side  only  the  afferent  fibres  are  shown; 
the  efferent  fibres  and  the  spinal  cells  on  the 
right  side.  D.R.,  posterior  (dorsal)  root; 
V.R.,  anterior  (ventral)  root;  C.P.,  crossed 
pyramidal  fibres;  C,  direct  cerebellar  tract; 
A.L.,  antero-lateral  tract;  D.C.,  posterior 
columns. 


THE  CENTRAL  NERVOUS  SYSTEM 


descending.     The  septo-marginal  bundle  consists  also  largely  of  fibres 
which  begin  and  end  in  the  cord  (proprio-spinal  fibres).  Some  endog- 


Fig.  335. — Medulla  Oblongata,  Pons  and 
Corpora  Quadrigemina  (Dorsal  or  Pos- 
terior View)  (Sappey).  i,  corpora 
quadrigemina;  2,  nates;  3,  testes; 
4,  anterior  brachium  uniting  the  nates 
to  the  lateral  geniculate  body;  5,  pos- 
terior brachium  uniting  the  testes  to 
the  internal  geniculate  body  6;  7,  pos- 
terior commissure;  8,  pineal  gland 
pulled  forward  to  show  nates;  9,  su- 
perior peduncle  of  the  cerebellum;  10, 
II.  12,  valve  of  Vieussens;  13,  troch- 
lear nerve;  14,  lateral  sulcus;  15,  fillet; 
16,  superior,  17,  middle,  and  18,  in- 
ferior, peduncle  of  the  cerebellum; 
19,  floor  of  fourth  ventricle;  20,  audi- 
tory nerve;  21,  spinal  cord;  22,  postero- 
median column,  continued  in  the  me- 
dulla as  the  funiculus  gracilis;  23,  the 
clava,  the  continuation  of  the  funiculus 
gracilis. 


Fig.  336. — Medulla  Oblongata,  Pons 
and  Crura  Cerebri  (Ventral  or  An- 
terior View).  I,  infundibulum ; 
2,  tuber  cinereum;  3,  corpus  mam- 
millare;  4,  cerebral  peduncle  or  crus 
cerebri;  5,  pons;  6.  middle  peduncle 
of  cerebellum;  7,  pyramid;  8,  decus- 
sation of  pyramids;  9,  olive;  10,  tu- 
bercle of  Rolando  ;  11,  external 
arcuate  fibres ;  12,  upper  end  of  cord ; 
13,  ligamenlum  deuticulatum;  14, 
dura  mater  of  cord;  15,  optic  tract; 
16,  chiasma;  17,  third  nerve;  18, 
fourth  nerve;  19,  fifth  nerve;  20, 
sixth  nerve;  21,  seventh  nerve;  22. 
eighth  nerve;  23,  nerve  of  VVrisberg 
(portio  intermedia),  which  unites 
with  the  facial;  24,  glosso-pharyn- 
geal  nerve;  25,  vagus;  '26,  spinal 
accessory;  27,  hypoglossal;  28,  29, 
30,  first,  second,  and  third  pairs  of 
cervical  spinal  nerves. 


enous  fibres  may  also  be  intermingled  with  the  fibres  of  certain  of 
the  long  tracts,  both  in  the  antero-lateral  and  posterior  columns,  and 


GREY  AND  WHITE  MATTER  IN  CEREBROSPINAL  AXIS      841 

Sherrington  has  shown  (in  the  dog)  that  long  proprio-spinal  fibres 
passing  down  in  the  lateral  column  connect  the  upper  with  the  lower 
parts  of  the  cord  (p.  880). 

The  next  question  which  arises  is:  How  are  the  long  tracts  con- 
nected below — i.e.,  with  the  periphery — and  above — i.e.,  with  the 
higher  parts  of  the  central  nervous  system  ?  The  answer  to  this 
question,  partly  derived  from  clinical  records  and  partly  from 
experimental  results,  is  in  the  case  of  some  of  the  tracts  unexpectedly 
full  and  minute,  though  meagre  in  regard  to  others.  But  to  render 
it  intelligible  it  is  necessary,  first  of  all,  to  describe  briefly — 


Section  IV.— Arrangement  of  Grey  and  White  Matter 
IN  THE  Upper  Portion  of  the  Cerebro-Spinal  Axis. 

In  the  medulla  oblongata  the  grey  and  white  matter  of  the  spinal 
cord  is  rearranged,  and,  in  addition,  new  strands  of  fibres  and  new 
nuclei  of  grey  substance  make  their  appearance.  Of  these  nuclei  the 
most  conspicuous  is  the 
dentate  nucleus  of  the  in- 
ferior olive,  which,  covered 
by  a  crust  of  white  fibres, 
appears  as  a  projection  on 
the  antero-lateral  surface 
of  the  medulla.  In  front 
of  the  olive,  between  it 
and  the  continuation  of 
the  anterior  median  fis- 
sure, is  another  projec- 
tion, the  pyramid,  which 
looks  like  a  prolongation 
of  the  anterior  column  of 
the  cord,  but  is  made  up 
of  very  different  consti- 
tuents. Dorsal  to  the 
olive  is  the  restiform  body 
or  inferior  peduncle  of  the 
cerebellum,  and  behind 
the  restiform  body  lie  two 
thin  columns,  the  funicu- 
lus cuneatus,  which  con- 
tinues the  postero-extcr- 
nal  column  of  the  cord, 
and  the  funiculus  gracilis. 
which  continues  the  pos- 
tero-internal  column.  In 
these  funiculi  are  contained  collections  of  small  or  medium-sized  nerve- 
cells  termed  respectively  the  nucleus  cuneatus  and  the  nucleus  gracilis. 
The  rearrangement  of  the  constituents  of  the  cord  is  due  mainly  to  two 
causes:  (i)  The  opening  up  of  the  central  canal  to  form  the  fourth 
ventricle,  and  the  folding  out,  on  either  side,  of  the  grey  matter  which 
lies  posterior  to  it  in  the  cord;  (2)  the  breaking  up  of  the  grey  matter 
of  the  anterior  horn  by  strands  of  fibres  as  they  sweep  through  it  from 
the  lateral  pyramidal  tract  to  take  up  a  position  in  the  pyramid  of  the 
opposite  side  (decussation  of  the  pyramids),  and  a  little  higher  up  by 


Fig.  337. — Medulla  Oblongata  and  Cerebellum,  with 
Fourth  Ventricle  (Hirschfeld).  i,  mesial  groove 
of  floor  of  ventricle  running  down  to  the  calamus 
scriptorius;  2,  striae  acusticae;  3,  inferior  peduncle 
of  the  cerebellum;  4,  clava;  5,  superior  peduncle 
crossing  the-  inferior  and  passing  to  its  internal 
side;  7,  7,  lateral  sulcus;  8,  corpora  quadrigemina. 


842  THE  CENTRAL  NERVOUS  SYSTEM 

fibres  passing  across  the  middle  line  from  the  gracile  and  cimcate  nuclei 
(sensory  decussation  or  decussation  of  the  fillet).  The  mosaic  of  grey 
and  white  matter  formed  in  the  medulla  by  the  interlacing  of  longi- 
tudinal and  transverse  fibres  with  each  other  and  with  the  relics  of  the 
anterior  horn,  is  called  the  reticular  formation  {formatio  reticularis). 
It  occupies  the  anterior  and  lateral  portions  of  the  bulb  behind  the 
pyramids  and  olivary  bodies,  and  is  continued  upwards  in  the  dorsal 
portion  of  the  pons  and  crura  cerebri,  and  downwards  for  a  little  way 
into  the  upper  part  of  the  cervical  cord. 

The  cerebro-spinal  axis  passes  up  from  the  medulla  through  the  pons, 
encircled  and  traversed  by  the  transverse  pontine  fibres  derived  from 
the  middle  cerebellar  peduncle  or  commissure,  which  enclose  every- 
where between  them  numerous  collections  of  nerve-cells  [nuclei  pontis). 
Enlarged  by  the  accession  of  many  of  these  fibres  which  come  from  the 
cortex  of  the  cerebellum  on  the  opposite  side,  as  well  as  of  fibres  from  the 
nuclei  of  the  cranial  nerves  that  take  origin  in  this  neighbourhood  (fifth 
and  eighth),  the  central  nervous  stem  bifurcates  above  the  pons  into  the 
two  divergent  crura  cerebri.  From  each  crus  a  great  sheet  of  fibres 
passes  up  between  the  optic  thalamus  and  the  caudate  nucleus  of  the 
corpus  striatum  on  the  one  hand,  and  the  globus  pallidus  of  the  lenticular 
nucleus  on  the  other,  as  the  internal  capsule,  from  which  they  are  dis- 
persed, in  the  corona  radiata,  to  the  cerebral  cortex.  Both  in  the  upper 
part  of  the  pons  and  in  the  crus  a  ventral  portion,  or  crusta,  containing 
the  fibres  of  the  pyramidal  tract,  and  a  dorsal  portion,  or  tegmentum, 
can  be  distinguished,  the  line  of  separation  being  marked  in  the  crus  by 
a  collection  of  grej^  matter,  called  from  its  usual,  though  not  invariable, 
colour  the  substantia  nigra  (Fig.  342).  A  portion  of  the  tegmentum  is 
continued  below  the  optic  thalamus. 


Section  V. — Connections  of  the  Long  Paths  of  the  Cord. 

Coming  back  now  to  our  question  as  to  the  connections  of  the  long 
tracts  of  the  cord,  let  us  consider,  first  of  all. 

The  Connections  of  the  Postero-Median  and  Postero-External 
Columns. — When  a  single  posterior  root  is  divided,  say,  in  the  dorsal 
region,  between  the  cord  and  the  ganglion,  its  fibres,  as  we  have 
already  seen  (p.  771),  degenerate  above  the  section.  Since  the  cell- 
bodies  of  these  neurons  lie  in  the  ganglion,  if  a  series  of  microscopic 
sections  of  the  spinal  cord  be  made,  well-marked  degeneration  will 
be  found  at  the  level  of  entrance  of  the  root  on  the  same  side  of  the 
cord,  while  below  that  level  there  will  be  only  a  few  degenerated 
fibres  in  the  comma  tract.  Immediately  above  the  plane  of  the 
divided  root  the  degeneration  will  be  confined  to  Burdach's  column 
and  to  its  external  border.  Higher  up  it  will  be  found  in  the  internal 
portion  of  Burdach's  and  the  external  rim  of  Goll's  column.  Still 
higher  up  the  degenerated  fibres  will  be  confined  to  the  postero- 
median column;  the  postero-external  will  be  free  from  degeneration. 

When  a  number  of  consecutive  posterior  roots  are  cut,  the  whole 
of  the  postero-external  column  in  the  sections  immediately  above 
the  highest  of  the  divided  roots  will  be  found  occupied  by  degene- 
rated fibres,  while  Goll's  column  may  be  free  from  degeneration,  or 


tr^r^ 


CONNECTIONS  OF  THE  LONG  PATHS  OF  THE  CORD         843 

degenerated  only  at  its  outer  border.  Higher  up  degeneration  will 
be  found  to  have  involved  the  whole  of  the  postero-median  column, 
and  to  have  cleared  away  altogether  from  the  postero-exti-rnal. 
The  degeneration  in  the  column  of  GoU  may  be  traced  along  the 
whole  length  of  the  cord  to  the  medulla,  although  the  number  of 
degenerated  fibres  diminishes  as  we  pass  upward.  The  explanation 
of  these  appearances  is  as  follows:  It  may  be 
seen  in  preparations  of  the  cord  impregnated  by 
Golgi's  method  that  the  fibres  of  the  posterior 
roots  soon  after  their  entrance  into  the  cord 
divide  into  two  processes,  one  of  which  runs  up 
and  the  other  down  in  the  posterior  column,  or 
in  the  adjoining  portion  of  the  posterior  horn. 
From  both  of  these  collaterals  are  given  off  at 
intervals  to  the  grey  matter.  The  descending 
branches  run  downwards  only  for  a  short  dis- 
tance, and  the  degeneration  in  the  comma  tract 
seen  after  section 
of  the  cord  is  due 
to  the  division  of 
these  branches. 
Many  of  the  as- 
cending branches 
pass  up  for  a  short 
distance  in  the 
postero-external 
column,  sweeping 
obliquely  through 
it  to  gain  the  tract 
of  Goll.  In  this 
tract  some  of  them 
run  right  on  to 
the  medulla  ob- 
longata, to  end  by 
arborizing  among 
the  cells  of  the 
nucleus  gracilis. 
Other  fibres,  both 
of  Goll's  and  of 
Burdach's  tract, 
end  at  various 
levels  in  the  cord, 
their  collaterals,  and  ultimately  the  main  branches  themselves, 
coming  into  relation  with  nerve-cells  in  the  grey  matter.  When  the 
cervical  posterior  roots  are  cut,  many  of  the  degenerated  fibres 
remain  in  Burdach's  column  up  to  the  medulla,  where  they  terminate 


Fig.  338.— Diagrams 
of  Degeneration  at 
Different  Levels  in 
the  Cord  after  Sec- 
tion of  a  Number  of 
Posterior  Roots  of 
Nerves  forming  the 
Lumbo-Sacral  Plex- 
us (Mott). 


Pig-  339- — Branrhing  of  Posterior 
Koot-Fibres  in  Cord  (Donald- 
son, after  Cajal).  Collaterals, 
Col,  are  seen  coming  oft  from 
the  two  main  branches  of  the 
root-fibres,  DR,  and  ending  in 
arborizations.  CC.  cells  in  the 
grey  matter  of  the  cord,  whose 
axons  also  give  off  collaterals. 


844  2^^"^  CENTRAL  NERVOUS  SYSTEM 

in  the  nucleus  cuneatus.  In  the  posterior  column,  then,  the 
numerous  fibres  of  the  posterior  roots  which  do  not  end  in  the  spinal 
cord  are  arranged  in  layers,  the  fibres  from  the  lower  roots  being 
nearest  the  median  fissure  (in  the  postero-median  column),  and  those 
from  the  higher  roots  farthest  away  from  it  (in  the  postero-extemal 
column.  Thus,  in  a  section  through  the  upper  cervical  region  GoU's 
column  is  almost  entirely  composed  of  fibres  from  the  posterior  limb, 
while  the  column  of  Burdach  consists  of  fibres  from  the  anterior 
limb.  Other  collaterals  from  the  posterior  root-fibres,  and  many 
of  the  main  root-fibres  themselves,  run  into  the  anterior  horn  and 
terminate  in  arborizations  around  its  cells;  some  pass  into  the 
posterior  horn,  and  doubtless  come  into  relation  with  its  scattered 
cells  and,  in  the  dorsal  region,  with  the  cells  of  Clarke's  column. 
Some  of  the  posterior  root-fibres  and  their  collaterals  also  form 
synapses  .with  the  cells  of  the  intermedio-lateral  tract.  Other 
collaterals  and  probably  some  axons  cross  the  middle  line  in  the 
anterior  and  posterior  commissures  and  end  in  the  grey  matter  of  the 
opposite  side. 

Connections  of  the  Direct  or  Dorsal  Cerebellar  Tract. — Since  the 
dorsal  or  direct  cerebellar  tract  does  not  degenerate  after  section  of 
the  posterior  nerve-roots,  but  does  degenerate  above  the  level  of  the 
lesion  after  section  of  the  spinal  cord,  the  nerve-cells  from  which  its 
axons  arise  must  be  situated  somewhere  or  other  in  the  cord.  Now, 
it  has  been  observed  that  the  vesicular  column  of  Clarke  first  becomes 
prominent  in  the  lower  dorsal  region,  and  that  in  this  same  region 
the  direct  cerebellar  tract  begins.  Atrophy  of  the  cells  of  Clarke's 
column  has  sometimes  in  disease  been  shown  to  accompany  de- 
generation of  the  direct  cerebellar  fibres.  After  an  experimental 
lesion  of  these  fibres  in  animals,  some  of  the  cells  of  the  vesicular 
column  show  the  changes  in  the  Nissl  bodies  and  the  other  changes 
which  we  have  already  described  as  occurring  in  nerve-cells  whose 
axons  have  been  cut.  After  two  or  three  months  these  cells  may 
be  found  almost  completely  atrophied  (Schafer).  Finally,  axis- 
cylinder  processes  have  been  seen  sweeping  out  from  Clarke's 
column  into  the  direct  cerebellar  tract  (Mott).  The  evidence,  then, 
is  complete  that  the  cells  of  origin  of  this  tract  are  in  Clarke's  column. 
Clarke's  cells  are  surrounded  by  arborizations,  some  of  which,  as 
previously  stated,  represent  the  terminations  of  posterior  root-fibres 
and  of  their  collaterals.  The  neurons  whose  axons  run  in  the  dorsal 
cerebellar  tract  are  therefore  the  second  link  in  an  afferent  path. 
The  direct  cerebellar  tract  runs  right  up  to  the  cerebellum  through 
the  restiform  body,  without  crossing  and  without  being  further 
interrupted  by  nerve-cells.  The  restiform  body  ends  partly  in  the 
dentate  nucleus  of  the  cerebellum,  partly  in  the  vermis,  and  among 
the  fibres  which  end  in  the  vermis  are  those  of  the  direct  cerebellar 
tract.     In  the  dorsal  cerebellar  tract  there  is  a  definite  stratification 


CONNECTIONS  OF  THE  LONG  PATHS  OF  THE  CORD 


845 


of  the  fibres:  the  fibres  from  the  lowest  segments  of  the  cord  lie 
outermost;  beneath  these  come  fibres  from  the  lowest  thoracic  seg- 
ments, then  fibres  from  the  higher  thoracic  segments;  and,  internal 
to  all,  fibres  from  the  topmost  thoracic  and  lowest  cervical  segments. 

Connections  of  the  Antero-Lateral  Ascending  Tract. — According  to 
Schiifcr,  the  axons  of  this  tract  arc  probably  connected  with  cells 
situated  in  the  middle  and  posterior  parts  of  the  grey  crescent,  mainly 

nX'    t 


I'ig.  340. — Transverse  Section  of  Medulla 
Oblongata  at  the  Level  of  the  Decussa- 
tion of  the  Fillet  (Halliburton,  after 
Schwalbe).  a.m.f,  anterior,  and  p.m./, 
posterior,  median  fissure;  f.a  and  f.a^, 
external  arcuate  fibres;  f.a',  internal 
arcuate  fibres  becoming  external;  n.a.r, 
nuclei  of  arcuate  fibres;  py,  pyramid; 
o,  0',  lower  end  of  nucleus  of  olive ;  f.r, 
formatio  reticularis;  n.l,  lateral  nucleus; 
n.g,  nucleus  gracilis;  f.g,  funiculus  gra- 
cilis; n.c,  nucleus  cuneatus;  n.c',  external 
cuneate  nucleus; /.c,  funiculus  cuneatus; 
g,  substance  of  Rolando;  c.c,  central  canal 
surroundedby  grey  matter;  n.  AT/,  nucleus 
of  spinal  accessory;  n.XII,  of  hypoglos- 
sal; a.V,  ascending  root  of  fifth  nerve; 
s.d,  the  decussation  of  the  fillet,  or 
superior  decussation. 


Fig.  341. — Transverse  Section  of  Medulla 
Oblongata  at  about  the  Middle  of  the 
Olive  (Schwalbe).  f.l.a,  anterior  median 
fissure;  n.a.r,  arcuate  nucleus;  p.,  pyra- 
mid; n.XII,  hypoglossal  nucleus;  XII, 
root  bundle  of  hypoglossal  nerve  coming 
off  from  the  surface ;  at  6  it  runs  between 
the  pyramid  and  the  dentate  nucleus  of 
the  olive,  0;  f.a.e,  external  arcuate  fibres; 
n.l,  lateral  nucleus;  a,  arcuate  fibres  going 
to  restiform  body  c.r,  partly  through  the 
substantia  gelatinosa  g,  partly  superficial 
to  the  ascending  root  of  the  fifth  nerve 
a.V ;  X,  root-bundle  of  vagus;  fi..V.  n.X', 
two  portions  of  vagus  nucleus;  f.r,  for- 
matio reticularis;  n.g,  nucleus  gracilis; 
n.c,  nucleus  cuneatus;  n.t.  nucleus  of  the 
funiculus  teres;  n.atn,  nucleus  ambiguus; 
r,  raphe;  o',  o',  accessory  olivary  nucleus; 
p.o.l.  peduncle  of  the  olive. 


on  the  opposite  side  of  the  cord,  although  also  on  the  same  side.  None  of 
the  fibres  of  the  tract  can  come  directly  from  the  posterior  nerve-roots, 
since  no  degeneration  is  seen  in  it  on  section  of  the  roots  alone. 

The  antcro-lateral  ascending  tract  passes  up  through  the  medulla, 
where  some  of  its  fibres  perhaps  form  synapses  with  the  cells  of  the 


846 


THE  CENTRAL  NERVOUS  SYSTEM 


lateral  nucleus,  a  collection  of  grey  matter  in  the  lateral  portion  of  the 
spinal  bulb.  But  its  main  strand  runs  on  unbroken  through  the 
medulla,  in  front  of  the  restiform  body,  and  behind  the  olive,  and  after 
reaching  the  upper  part  of  the  pons  bends  back  over  and  in  company 
with  the  superior  peduncle  as  the  ventral  spino-cerebellar  bundle,  to 
end  in  the  worm  of  the  cerebellum  (Fig.  353). 

A  few  fibres  of  Gowers'  tract  may  pass  by  the  middle  peduncle  to  the 
opposite  cerebellar  hemisphere.  Some  of  its  fibres  do  not  go  to  the 
cerebellum  at  all.  One  group  can  be  followed  to  the  corpora  quadri- 
gemina  {spino-tectal  fibres),  and  another  by  way  of  the  tegmentum  of  the 
crus  cerebri  to  the  optic  thalamus  {spino-thalainic  fibres). 

Through  the  relay  of  the  gracile  and  cuneate  nuclei,  the  postero- 
internal and  postero-external  columns  of  the  cord  are  further  con- 
nected on  the  one  hand  with  the  cerebrum,  and  on  the  other  with  the 
cerebellum.  The  cells  of  the  nuclei  give  off  fibres  (internal  arcuate 
fibres)  which,  sweeping  in  wide  arches  across  the  mesial  raphe  to  the 

opposite  side,  take  up 
a  position  behind  the 
pyramid  in  the  tract  of 
the  fillet,  a  bundle  of 
fibres  which  becomes 
more  compact,  and 
therefore  more  distinct, 
as  it  passes  brainwards. 
Receiving  fibres  from 
other  sources  on  its 
way,  and  also  giving 
off  fibres,  it  runs  up- 
wards through  the  dor- 
sal or  tegmental  portion 
of  the  pons.  In  the  mid- 
brain it  divides  into 
two  portions,  the  lateral 
fillet,  also  called  the 
lower  fillet  or  fillet  of  Reil,  and  the  intermediate,  also  called  the  upper 
fillet.  The  lateral  fillet  contains  mainly  fibres  arising  in  the  cochlear 
nucleus  of  the  auditory  never,  and  ends  in  grey  matter  of  the  pos- 
terior corpus  quadrigeminum,  and  partly  in  the  mesial  geniculate 
body.  It  appears  to  be  a  path  for  the  conduction  of  auditory 
impulses.  The  intermediate  fillet  contains  chiefly  the  fibres  that 
come  off  from  the  gracile  and  cuneate  nuclei,  but  is  enlarged  by  the 
accession  of  fibres  from  the  sensory  nuclei  of  the  cranial  nerves.  It 
terminates  in  the  lateral  nucleus  of  the  optic  thalamus  by  forming 
synapses  with  nerve-cells,  whose  axons,  passing  through  the  posterior 
limb  of  the  internal  capsule  and  the  corona  radiata,  continue  the 
afferent  path  to  the  cerebral  cortex. 

Not  all  of  the  axons  from  the  cells  of  the  cranial  sensory  nuclei  run 


Fig.  342. — Diagrammatic  Transverse  Section  of 
Crura  Cerebri  and  Aqueduct  of  Sylvius,  a,  an- 
terior corpora  quadrigemina  h,  aqueduct;  c,  red 
nucleus;  d,  fillet;  e,  substantia  nigra;/,  pyramidal 
tract  in  the  crusta  of  the  crura  cerebri;  g,  fibres 
from  frontal  lobe  of  cerebrum;  h,  fibres  from  tem- 
poro-occipital  lobe ;  /',  posterior  longitudinal  bundle. 


CONNECTIONS  OF  THE  LONG  PATHS  OF  THE  CORD 


847 


in  the  fillet.  Many  of  them  occupy  a  position  in  the  reticular  forma- 
tion of  the  tegmentum  dorsal  to  the  fillet  as  they  pass  through  the 
pons  and  mid-brain  to  end  in  the  thalamus  and  the  region  below  it 
(sub-thalamic  region).  From  the  sensory  nucleus  of  the  fifth  nerve 
a  separate  bundle  ot  fibres  ascends  to  the  thalamus,  in  the  tegmen- 
tum of  the  mid-brain  lateral  to  the  posterior  longitudinal  bundle. 
-^  Connections  of  the  Pyramidal  Tracts. — When  the  cortex  in  and  in 
front  of  the  fissure  of  Rolando  is  destroyed  by  disease  in  man,  or 
removed  by  operation  in  animals,  it  is  found  that  in  a  short  time 
degeneration  has  taken  place  in  the  fibres  of  the  corona  radiata  which 
pass  off  from  this  area.  The  degeneration  can  be  followed  down 
through  the  genu  and  the  anterior  two-thirds  of  the  posterior  limb 
of  the  internal  capsule  r 

(Fig.  343)  and  the 
crusta  of  the  cerebral 
peduncle  of  the  corre- 
sponding side  into  the 
medulla  ojblongata. 
Below  the  decussation 
of  the  pyramids  it  is 
found  that  the  degene- 
ration has  involved  the 
two  pyramidal  tracts, 
and  only  these  —  the 
crossed  pyramidal 
tract  on  the  side  oppo- 
site the  cortical  lesion, 
the  direct  pyramidal 
tract  on  the  same  side 
— and  that  the  cross- 
section  of  the  two  de- 
generated tracts  goes 
on  continually  dimin- 
ishing as  we  pass  down  the  cord.  (We  overlook  for  the  moment,  in 
the  interest  of  simplicity  of  statement,  the  fact  that  some  degenerated 
fibres  are  found  in  the  crossed  pyramidal  tract  on  the  same  side  as  the 
lesion.)  This  is  proof  positive  that  the  cell-bodies  of  the  neurons  whose 
axons  run  in  these  tracts  are  situated  in  the  cerebral  cortex.  They 
have  indeed  been  identified  with  certain  of  the  large  pyramidal  cells 
(the  so-called  giant  cells  or  cells  of  Betz)  in  the  cortex  of  the  '  motor  ' 
region  in  front  of  the  Rolandic  fissure  (p.  918).  For  after  division 
of  the  motor  pyramidal  fibres  in  the  upper  cervical  region  of  the  cord 
(in  monkeys)  changes  in  the  chromatin  (so-called  chromatolysis)  and 
atrophy  of  these  large  cells  occur.  The  same  has  been  found  to  be 
true  in  man  in  cases  where  the  cord  was  injured  by  fracture  of  the 
spine  in  such  a  way  as  to  interrupt  the  tract  (as  well  as  other  tracts) 


CORD 


MID.  BRAIN 


Fig-  343. — Pyramidal  Path  (after  Gowers).  Degenera- 
tion after  destruction  of  the  '  motor  '  area  of  the 
right  cerebral  hemisphere.  The  degenerated  areas 
are  indicated  by  the  shading. 


848  THE  CENTRAL  NERVOUS  SYSTEM 

completely  and  permanently,  without  entailing  death  for  a  consider- 
able time  (Holmes  and  May).  The  fact  that  after  destruction  of  the 
cortex  or  the  path  in  its  course  the  degeneration  below  the  lesion  does 
not  spread  to  the  anterior  roots  shows  that  at  least  one  relay  of 
nerve-cells  intervenes  between  the  pyramidal  fibres  and  the  root- 
fibres.  The  results  both  of  normal  and  morbid  histology  enable  us 
to  identify  the  cells  of  the  anterior  horn  as  the  cells  of  origin  of  the 
axons  of  the  anterior  root-fibres.     For 

(i)  Axis-cylinder  processes  have  been  actually  observed  passing  out 
from  certain  of  the  so-called  motor  cells  of  the  anterior  horn  to  become 
the  axis-cylinders  of  the  anterior  root. 

(2)  In  the  pathological  condition  known  as  anterior  poliomyelitis, 
the  cells  of  the  anterior  horn  degenerate,  and  so  do  the  anterior  roots 
of  the  affected  region,  the  motor  fibres  of  the  spinal  nerves,  and  the 
muscles  supplied  by  them. 

(3)  As  already  mentioned  (p.  830),  comparatively  transient  but 
decided  changes  occur  in  the  anterior  horn  cells  on  section  of  the  corre- 
sponding anterior  roots. 

(4)  An  enumeration*  has  been  made  in  a  small  animal  (frog)  of  the 
cells  of  the  anterior  horn  and  of  the  anterior  root-fibres,  and  it  has  been 
found  that  the  numbers  agree  in  a  remarkable  manner.  From  all  this 
it  cannot  be  doubted  that  most,  at  any  rate,  of  the  cells  of  the  anterior 
horn  are  connected  with  fibres  of  the  anterior  root.  But  since  the 
number  of  fibres  in  the  pyramidal  tracts  (about  80,000  in  each  half  of 
the  human  cord)  falls  far  short  of  the  number  of  fibres  in  the  anterior 
roots  (not  less  than  200,000  in  man  on  each  side),  it  is  necessary  to 
suppose  either  that  one  pyramidal  fibre  may  be  connected  with  several 
cells  or  that  all  the  anterior  root-fibres  are  not  in  functional  connection 
with  the  pyramidal  tract. 

There  is  no  reason  to  assume  any  such  connection  in  the  case  of  the 
fine  meduUated  root-fibres  arising  in  the  lateral  horn  and  going  to  the 
visceral  and  vascular  muscles. 

While  there  is  no  doubt  that  anterior  root-fibres  and  pyramidal 
fibres  of  the  brain  and  cord  form  segments  of  the  same  nervous  path, 
the  connection  between  the  pyramidal  fibres  and  the  cells  of  the 
anterior  horn  has  not  yet  been  anatomically  demonstrated.  Many  of 
the  pyramidal  fibres  pass  into  the  grey  matter  between  the  anterior 
and  posterior  horns  or  near  the  base  of  the  posterior  horn.  The 
anterior  horn  cells  are  surrounded  by  arborizations.  Some  of  these 
are  probably  the  terminations  of  axons  whose  cell-bodies  are  situated 
in  the  posterior  horn,  others  the  terminations  of  posterior  root-fibres 
or  their  collaterals.  Many  of  them  very  likely  represent  the  end 
arborizations  of  pyramidal  fibres  or  their  collaterals.  Some  ob- 
servers, however,  suppose  that  the  pyramidal  fibres  do  not  come  into 
immediate  relation  with  the  anterior  horn  cells,  but  that  another 
neuron  is  intercalated  between  them  and  the  cells. 

The  pyramidal  fibres  are  unquestionably  paths  for  voluntary 
motor  impulses  passing  down  from  the  cortex  to  the  cord.     But 

*  Such  enumerations  can  be  made  with  great  accuracy  from  photographs 
of  sections  of  the  nerves  (Hardesty,  Dale).     (See  Fig.  331,  p.  832.) 


CONNECTIONS  OF  THE  LONG  PATHS  OF  THE  CORD       S49 

they  are  not  the  only  cortico-spinal  efferent  paths,  and  in  many 
animals  they  are  not  even  the  most  important  paths  for  voluntary 
movements.  It  is  the  more  skilled  and  delicate  movements  which 
the  pyramidal  tract  subserves  in  man,  and  it  is  these  movements 
which  arc  permanently  lost  when  the  tract  is  destroyed.  The  size 
of  the  path  is  proportioned  to  the  degree  of  development  of  the 
brain.  Thus,  it  is  larger  in  the  monkey  than  in  the  dog,  larger  in  the 
anthropoid  apes  than  in  the  lower  monkeys,  and  larger  in  man  than 


Fig-  344- — Paths  from  Corte.x  in  Corona  Radiata  (Starr).  A,  tract  from  frontal  con- 
volutions to  nuclei  of  pons  and  so  to  cerebellum;  B.  motor  pyramidal  tract; 
C,  afferent  tract  for  tactile  sensations  (represented  in  the  diagram  as  separated 
from  B  by  an  interval  for  the  sake  of  clearness);  D,  visual  tract;  E,  auditory 
tract;  F,  G,  H,  superior,  middle,  and  inferior  cerebellar  peduncles;  J,  fibres 
from  the  auditory  nucleus  to  the  posterior  corpus  quadrigeminum;  K,  decussa- 
tion of  the  pyramids  in  the  bulb;  FV,  fourth  ventricle.  The  romaa  numerals 
indicate  the  cranial  nerves. 

in  even  the  highest  of  the  apes.  In  the  lower  mammals  it  is  exceed- 
ingly small.  While  in  man  the  pyramidal  tracts  constitute  nearly 
12  per  cent,  of  the  total  cross-section  of  the  cord,  they  make  up 
little  more  than  i  per  cent,  in  the  mouse,  3  per  cent,  in  the 
guinea-pig,  5  per  cent,  in  the  rabbit,  and  nearly  8  per  cent,  in  the  cat. 
In  some  mammals,  as  the  rat,  mouse,  guinea-pig,  and  squirrel,  the 
pyramidal  tracts  lie,  not  in  the  antero-lateral,  but  in  the  posterior 
columns.  In  vertebrates  below  the  mammals  the  pyramidal  system 
does  not  exist  as  a  collection  of  neurons  which  send  their  axons  with- 

54 


850 


THE  CENTRAL  NERVOUS  SYSTEM 


out  interruption  down  from  the  cortex  to  the  cord.  In  birds,  e.g., 
after  the  removal  of  a  hemisphere,  the  degeneration  does  not  extend 
below  the  mid-brain  (Boyce). 


Section  VI. — Paths  from  and  to  the  Cortex. 
Thus  far  we  have  been  able  to  map  out  two  great  paths  from 
the  cerebral  cortex  to  the  periphery — one  efferent,  the  other  afferent, 
(i)  The  great  efferent  or  motor  pyramidal  path,  which,  starting  in 
the  cortex  in  front  of  the  fissure  of  Rolando,  where  its  axons  give  off 
numerous  collaterals  to  the  grey  matter  soon  after  emerging  from 
the  cells,  and  sweeping  down  the  broad  fan  of  the  corona  radiata, 

passes  through  the  narrow 
isthmus  of  the  internal  cap- 
sule into  the  crusta  of  the 
crus  cerebri,  and  thence  into 
the  pons  (Figs.  344,  345).  At 
this  level,  the  fibres  destined 
to  make  connection  with  the 
motor  nuclei  of  the  cranial 
nerves  in  the  grey  matter 
underlying  the  aqueduct  of 
Sylvius  and  the  fourth  ven- 
tricle terminate.  Most  of 
these  fibres  decussate  to  make 
physiological  connection  with 
nuclei  on  the  opposite  side, 
but  some  join  nuclei  on  the 
same  side.  The  question 
whether  they  arborize  di- 
rectly around  the  cells  of  the 
motor  nuclei  or  make  junc- 
tion with  them  through 
another  intercalated  neuron 
is  precisely  in  the  same 
position  as  the  corresponding 
question  for  the  spinal  pyra- 
midal path  (p.  848).  On  their 
way  through  the  pons  they  send  off  collaterals  to  the  nuclei 
pontis,  as  they  do  higher  up  to  the  grey  matter  of  the  basal 
ganglia  of  the  cerebrum  and  the  substantia  nigra,  and  the  path 
may  be  continued  to  the  motor  nuclei  by  axons  arising  here. 
There  is  no  proof,  however,  that  this  is  the  case.  The  rest  of 
the  pyramidal  fibres  run  on  into  the  pyramid  of  the  bulb, 
where  the  greater  part  (usually  about  go  per  cent.)  of  the  fibres 
decussate,  appearing  in  the  cervical  cord  as  the  massive  crossed 


Fig.  345. — Motor  Pyramidal  Tracts  (Diagram- 
matic) (Halliburton,  after  Gowers).  The 
convolutions  are  supposed  to  be  cut  in 
vertical  transverse  section,  the  internal 
capsule,  I,  C,  and  the  crus  in  horizontal 
section.  O,  TH,  optic  thalamus;  CN,  cau- 
date nucleus;  L2  and  L3,  middle  and  ex- 
ternal portions  of  lenticular  nucleus;  /,  a,  I, 
fibres  from  the  face,  arm,  and  leg  areas  of 
the  cortex  respectively;  E,  S,  Sylvian  fis- 
sure. The  genu  or  knee  of  the  internal 
capsule  is  indicated  by  the  asterisk. 


PATHS  FROM  AND  TO  THE  CORTEX 


85t 


pyramidal  tract  of  the  opposite  side.  A  few  (usually  about  lo  per 
cent.)  remain  on  the  same  side  as  the  slender  direct  pyramidal  tract. 
The  size  of  this  tract  varies  much  in  different  individuals,  and  it 
is  occasionally  absent.  Its  breadth  constantly  diminishes  as  it 
proceeds  down  the  cord,  and  it  disappears  before  the  middle  of  the 
thoracic  region  is  reached,  its  fibres  continually  decussating  across 
the  anterior  white  commissure  and  plunging  into  the  opposite 
anterior  horn.  They 
either  end  among  its 
cells,  or,  passing  through 
it,  reinforce  the  crossed 
pyramidal  tract.  The 
fibresof  thiscrossedtract 
are,  in  their  turn,  con- 
tinually passing  off  into 
the  grey  matter  to  make 
connection  (p.  848)  with 
the  cells  of  the  anterior 
horn,  whose  axis-cylin- 
der processes  enter  the 
anterior  roots  of  the 
spinal  nerves.  The  losses 
which  it  suffers  as  it 
descends  the  cord  may 
be  in  some  slight  degree 
compensated  by  the  bi- 
furcation of  some  of  its 
fibres  (geminal  fibres), 
but  ultimately  the  whole 
tract  forms  synapses 
with  cells  in  the  grey 
matter,  and  dwindles 
away  as  the  lumbar  re- 
gion is  reached(Fig.  333). 
A  certain  number  of  the 
pyramidal  fibres  do  not 
decussate  either  in  the 
bulb  or  in  the  cord. 
These  are  called  homo- 
lateral fibres.  They  run 
down  in  the  lateral  py- 
ramidal tract,  and  are 
represented  by  the  fibres 
that  degenerate  in  that 
tract  after  a  lesion  in  the  '  motor  '  area  of  the  same  side  (p.  847), 
This  would  explain  the  escape  in  hemiplegia  (paralysis  of  one  side 


Fig.  346. — Horizontal  Section  tnrough  the  Right 
Hemisphere  to  show  the  Constituents  of  the 
Internal  Capsule  (von  Monakow).  A.  knee  of 
corpus  callosum ;  B,  anterior,  B',  posterior,  horn  of 
lateral  ventricle;  C,  knee  of  internal  capsule; 
S,  sensory  fibres;  V,  visual  tract;  AH,  Amnion's 
horn;  Calc,  calcaruie  fissure;  T,  first,  T',  second, 
temporal  convolution;  OR,  optic  radiation;  Aud, 
auditory  tract ;  D,  retrolenticular  region  of  internal 
capsule;  lo,  lenticulo-optic  division  of  internal 
capsule;  CI,  claustrum;  op.,  operculum;  I,  island 
of  Reil;  E,  external  capsule;  Is.  lenticulo-striate 
division  of  internal  capsule;  F.  fibres  from  frontal 
lobe;  F'.  inferior  part  of  third  frontal  convolution; 
Th,  optic  thalamus;  Put,  putamen. 


852  THE  CENTRAL  NERVOUS  SYSTEM 

Corpus  CAlloSUm,,      . 


lirflo-Corrical  Fibrfs 


Rtd   Nucleus  . 

Subsf&.nfi6  Miprcx CK 

Ptdunck -^ 


-^-^^Penfa.f'd  NMcldgS 


S^ino-CerebelU 
Tra^cfs 

(Co-ordin&i'ion  & 
Muscular  Tone  j  ^ 

f^jrd.m^ 6  ^ ^ _,  _ 
D«c|>  Arcuafe  FIbrts 


Oorsil  Column  (direct) 

(stnst  of  poiifion     ^ 
•■   movemcnr/ 


Crosstd  Sensory  Fibres 
[P&m.  H£i.t&  Cold\ 
Ifouch  &  Pressure} 

Inferior  Oi'iVi 


SpiflJil  Ntrve 


Fig.  347. — Ascending  Nerve  Tracts  (after  Holmes). 


PATHS  FROM  AND  TO  THE  CORTEX  853 

of  the  body)  of  those  muscles  which  are  accustomed  to  work  with 
the  corresponding  muscles  on  the  opposite  side — e.g.,  the  respiratory 
muscles,  these  being  innervated  to  some  extent  from  both  cerebral 
hemispheres. 

(2)  A  great  afferent  or  sensory  path  b}^  which  some  at  least  of  the 
impulses  carried  up  through  the  posterior  roots  of  the  spinal  nerves, 
after  passing  through  various  relay's  of  nerve-cells,  reach  the  cortex 
of  the  cerebellum ;  or  the  upper  portions  of  the  central  grey  tube,  the 
corpora  quadrigemina  and  optic  thalamus;  or,  finally  (through  the 
tegmentum  and  the  posterior  limb  of  the  internal  capsule  behind  the 
motor  fibres),  the  cerebral  cortex  itself. 

The  efferent  pyramidal  path  from  the  cortex  to  the  periphery  is 
broken  by  at  most  two  relays  of  nerve-cells — those  intercalated  cells 
to  which  reference  has  already  been  made  (p.  848),  if  they  really 
exist,  and  the  motor  cells  of  the  anterior  horn.  The  afferent  path  to 
the  cerebral  cortex  is  interrupted  by  at  least  three  relays  with  axons 
of  considerable  length.  One  of  the  cells  is  situated  in  the  ganglion 
on  the  posterior  root,  another  in  the  medulla  oblongata,  a  third  in  the 
optic  thalamus ;  and  on  some  of  the  routes  another,  or  even  more  than 
one,  is  intercalated  between  the  medulla  and  the  cortex  (Fig.  347). 

The  Internal  Capsule. — We  have  already  recognized  the  pyramidal 
tract  and  the  afferent  tegmental  path  as  constituents  of  the  internal 
capsule.  The  cranial  fibres  of  the  pyramidal  tract  occupy  mainly 
the  genu  or  knee,  the  spinal  fibres  the  posterior  limb  as  far  back  as 
the  posterior  border  of  the  lenticular  nucleus  (Fig.  346). 

The  fibres  from  the  various  motor  areas  are  to  a  certain  extent 
arranged  in  order  in  the  capsule,  those  for  the  eyes  and  head  lying 
farthest  forward,  those  for  the  leg  farthest  back,  while  the  fibres 
going  to  the  face,  arm  and  trunk  occupy  intermediate  positions. 
The  separation,  however,  is  far  from  complete,  the  fibres  of  neigh- 
bouring regions  being  considerably  intermixed  (Hoche).  As  the 
tracts  pass  downwards  the  intermingling  becomes  continually 
greater  (Simpson  and  Jolly)  (Figs.  348,  349).  The  afferent  fibres 
from  the  thalamus  to  the  cortex,  which  we  have  described  as  the 
last  segment  of  the  afferent  tegmental  path,  lie  in  the  posterior  part 
of  the  posterior  limb.  But  here  again  there  is  no  absolutely  sharp 
line  of  demarcation.  Some  motor  fibres  are  intermingled  with  the 
sensory  in  the  posterior  part  of  the  capsule,  for  lesions  of  this  region 
produce  a  certain  degree  of  paralysis  as  well  as  anaesthesia  on  the 
opposite  side  of  the  body.  A  pure  capsular  hemianaesthesia — that 
is,  a  loss  of  sensation  on  the  opposite  side  due  to  a  lesion  in  the 
internal  capsule  and  unaccompanied  by  motor  defect — does  not 
appear  to  exist.  Accordingly  the  common  statement  that  the  efferent 
(motor)  path  occupies  the  anterior  two-thirds,  and  the  afferent 
(sensory)  path  the  posterior  third  of  the  posterior  limb  of  the 
internal  capsule,  while  tnie  in  a  general  sense,  is  not  strictly  correct. 


»54 


THE  CENTRAL  NERVOUS  SYSTEM 


The  destination  of  the  afferent  fibres  of  the  internal  capsule  has 
not  been  definitely  settled.  There  is  no  doubt  that  they  pass  up  to 
the  convolutions  around  the  fissure  of  Rolando  (central  convolu- 
tions), and  there  is  reason  to  believe  that  some  of  them  terminate  in 
the  '  motor  '  region  in  front  of  that  fissure,  although  many  of  the 
fibres  concerned  in  tactile  sensations  seem  to  end  in  the  ascending 
parietal  convolution. 

But  we  have  not  yet  exhausted  the  constituents  of  the  internal 

capsule.  Two  great  cones  of  fibres 
sweep  down  into  it,  one  from  the 
frontal,  the  other  from  the  occipital 
and  temporal  portions  of  the  cerebral 
cortex.  The  first  passes  through  its 
anterior  limb,  the  second  behind  the 
sensory  path  in  its  posterior  limb. 
The  cells  of  origin  of  the  frontal  fibres 
are  known,  and  those  of  the  occipital 
and  temporal  fibres  are  supposed,  to 
be  situated  in  the  cortex.  They  are 
therefore  efferent  fibres  as  regards 
the  cortex  (cortifugal).  Running  on 
through  the  crusta  of  the  cerebral 
peduncle  (Fig.  342),  the  frontal  tract 


Fig.  348. — Pyramidal  Tract  in  In- 
ternal Capsule  {Simpson  and 
Jolly).  Horizontal  section 
through  right  cerebral  hemi- 
sphere, cutting  fibres  of  internal 
capsule  transversely  at  an  upper 
level  a  little  below  the  upper 
surface  of  tke  lenticular  nucleus. 
The  extent  of  the  degeneration 
following  destruction  of  the 
whole  of  the  right  '  motor  '  cor- 
tex, except  the  '  head  and  eyes  ' 
area  (in  one  of  the  lower  mon- 
keys), is  shown.  Note  over- 
lapping of  fibres  from  face,  arm, 
and  leg  areas,  as  shown  by  ex- 
periments in  which  one  or  other 
of  these  areas  was  alone  re- 
moved. 


Fig.  349. — Pj'ramidal  Tract  in  Internal 
Capsule  at  Lower  Level  (Simpson  and 
Jolly).  CN,  head  of  caudate  nucleus; 
OT,  optic  thalamus;  CI,  claustrum. 


internal,  the  occipito-temporal  external,  they  end  in  the  grey 
matter  of  the  pons,  and  serve  as  one  segment  of  an  extensive 
connection  between  the  cerebral  and  the  cerebellar  cortex  of  the 
opposite  side,  the  other  segment  being  formed  by  neurons  whose 
cell-bodies  are  situated  in  the  pons,  and  whose  axons,  crossing 


PATHS  FROM  AND  TO  THE  CORTEX 


855 


the  middle  line,  pursue  their  course  through  the  middle  cerebellar 
peduncle,  to  terminate  in  the  superficial  grey  matter  of  the  cere- 
bellum. It  is  evident  that  the  junction  of  the  cerebral  cortex  with 
this  pontine  grey  matter,  through  and  into  which  so  many  nerve- 
tracts  pass,  multij)lies  the  number  of  possible  routes  by  which 
impulses  may  travel  between  one  part  of  the  brain  and  another. 
The  corpus  callosum  forms  a  mighty  link  between  the  two  cerebral 
hemispheres.  And  intertwined  in  the  corona  radiata  with  the 
callosal  fibres  are  other  systems,  of  which  it  is  especially  necessary 
to  mention  the  afferent  (cortipetal)  fibres  that  join  the  optic  thalamus 
with  nearly  every  part  of  the  cerebral  cortex.  Such  fibres  pass  from 
the  cells  of  the  grey  matter  of  the  thalamus  to  the  frontal  and  parietal 


Fig.  350. — Association  Fibres  (after  Starr).  Cerebral  hemisphere  seen  from  the  side. 
A,  A,  association  fibres  between  adjacent  convolutions;  B,  between  frontal  and 
occipital  lobes;  C,  cinguluin,  connecting  frontal  and  tenipori>  si'henoidal  lobes; 
D.  uncinate  fasciculus  between  frontal  and  temporal  regions;  E,  inferior  longi- 
tudinal bundle  between  occipital  and  temporo-sphenoidal  lobes;  O.T.,  optic 
thalamus;  C.N.,  caudate  nucleus. 

regions  through  the  anterior  border  of  the  internal  capsule  in  front  of 
the  frontal  fibres  previously  described  as  running  in  the  anterior 
limb  of  the  capsule  to  the  pons;  and  from  the  thalamus  to  the  occi- 
pital region  through  the  extreme  posterior  border  of  the  internal 
capsule,  behind  the  occipital  fibres  that  proceed  to  the  pons.  The 
fibres  that  connect  the  thalamus  with  the  occipital  cortex  are 
spoken  of  as  the  optic  radiation.  Some  of  the  fibres  of  the  optic 
radiation,  however,  proceed,  nftt  from  the  thalanuis,  but  from  the 
anterior  corpus  quadrigeminum  and  the  lateral  geniculate  body. 
The  thalamus  is  also  connected  with  the  cortex  of  the  temporal  lobe, 
with  the  cerebellum,  and  through  the  fillet  with  the  posterior  part  of 
the  tegmental  system,  the  medulla  oblongata  and  the  spinal  cord 
(p.  846).  Fibres  also  pass  from  the  inner  and  deeper  part  of  the 
thalamus  to  the  lenticular  nucleus  of  the  corpus  striatum.     The 


856 


THE  CENTRAL  NERVOUS  SYSTEM 


thalamus  must  be  regarded  as  a  great  sensory  centre  through  which 
afferent  impulses  stream  on  their  way  to  all  parts  of  the  cortex. 

The  fibres  which  connect  the  cerebral  cortex  with  lower  levels  of 
the  central  nervous  system  are  sometimes  grouped  together  as 
projection  fibres  in  contradistinction  to  the  commissural  and  associa- 
tion fibres.  Alarge  proportion  of  the  fibres  of  the  corona  radiata  are 
projection  fibres,  including  efferent  groups  (pyramidal  tract,  fronto- 
pontine fibres,  temporo- 
pontine fibres)  and  afferent 
groups  (the  fillet  system, 
thalamo-cortical  fibres  from 
the  grey  matter  of  the 
thalamus  to  the  cortex,  in- 
cluding the  optic  radiation). 

Section  VII. — Connections 
OF  Brain  Stem  with  Cord 
— Connections  of  Cere- 
bellum. 

Connections  of  the  Vestibulo- 
spinal or  Antero-Lateral  De- 
scending Tract.  —  The  main 
origin  of  these  fibres  is  the 
nucleus  of  Deiters,  a  collection 
of  large  multipolar  nerve-cells 
in  the  floor  of  the  fourth  ven- 
tricle near  the  inner  auditory 
nucleus.  This  nucleus  consti- 
tutes an  important  intermedi- 
ate station  between  the  cere- 
bellum and  the  cord.  Its 
cells  give  off  axons  which  pass 
into  the  posterior  longitudinal 
bundle  of  the  bulb  and  pons, 
mostly  to  the  bundle  of  the 
same  side,  but  partly  into  that 
of  the  opposite  side.  Here  the 
fibres  bifurcate  into  an  ascend- 
ing branch,  which  passes  up  to 
the  oculo-motor  nucleus,  and  a 
descending  {vestibulo  -  spinal) 
branch,  which  passes  down- 
wards to  the  spinal  cord  and 
enters   the    antero-lateral    de- 


Fig.  351. — Fibres  connecting  Frontal  and 
Temporo-Occipital  Lobes  with  Cerebellum, 
etc.  (Diagram)  (after  Gowers).  Fr,  frontal, 
Oc,  occipital  lobe;  interrupted  lines  indicate 
fibres  (TOC)  connecting  cerebellum  and 
temporo-occipital  cortex,  and  fronto-cere- 
bellar  fibres  (FC).  On  left  side  the  position 
of  these  two  groups  of  fibres  and  of  motor 
(pyramidal)  tract,  PY,  in  the  crus,  is  indi- 
cated by  letters.  The  pyramidal  tract  is 
seen  on  the  right  passuig  down  from  the 
Rolandic  area  through  posterior  limb  of 
internal  capsule  IC  (the  genu  or  knee  of 
which  is  indicated  by  asterisk)  to  decussate 
in  the  bulb.  AF,  ascending  frontal  convolu- 
tion; AP,  ascending  parietal  convolution; 
FR,  fissure  of  Rolando;  IPF,  intraparietal 
fissure;  PCF,  precentral  fissure;  Ipt,  crossed 
pyramidal,  apt,  direct  pyramidal  tract.       * 


scending  tract.  The  fibres  of 
this  tract  ultimately  pass  into  the  anterior  horn,  where  most  of  them 
end  by  arborizing  amongst  the  cells  of  the  horn.  Higher  up  corre- 
sponding fibres  from  the  posterior  longitudinal  bundle  arborize  in  the 
cranial  motor  nuclei. 

Connections  of  the  Rubro-Spinal  Tract. — These  fibres,  as  the  name 
given  to  tlie  bundle  implies,  originate  in  the  red  nucleus  and  run  down 
into  the  cord.     A  little  distance  froni  their  cells  of  origin  they  cross  the 


CONNECTIONS  OF  CEREBELLUM 


857 


median  line,  and  then  pass  down  first  in  the  tegmentum,  and  below  that 
in  the  lateral  column  of  the  bulb  and  cord.  On  their  way  they  come 
into  relation  with  the  motor  nuclei  of  the  cranial  nerves,  and  in  the 
cord  with  the  cells  of  the  anterior  horn.  It  is  obvious  that  in  contrast 
to  the  projection  fibres  the  fibres  of  the  rubro-spinal,  vestibulo-spinal. 
olivo-sjiinal.  and  thalamico-spinal  tracts  (p.  Hyj)  and  the  posterior 
longitudinal  bundle  connect  the  brain  stem  or  cerebral  axis  with  the 
cord,  or  different  le\els  of  the  l»rain  stem  with  each  other. 

Connections  of  the  Grey  Matter  of  the  Cerebellum  with  the  Periphery 
and  other  Parts  of  the  Central  Nervous  System.— Numerous  as  arc  the 
nervous  ties  of  the  cerebral  cortex,  those  of  the  grey  matter  of  the 
cerebellum  are,  in  proportion  to  its  mass,  still  more  extensive,  particu- 
larly as  regards  afferent  fibres,  and  perhaps  not  less  important. 

Speaking  broadly,  we  may  say  that  the  restiform  body  or  inferior 
peduncle  connects  chiefly  the  dentate  nucleus  and  the  grey  matter  of 
the  worm  with  the  spinal  cord  and  medulla  oblongata,  and  through 
them  with  the  periphery.     The  fibres  which  it  receives  from  the  direct 


ha^. 


Fig.  352. — Direct  Sensory  Cerebellar 
Path  of  Edinger.  D,  Deiters' 
nucleus;  v,  median  nucleus  of 
auditory  nerve;  t,  nucleus  of  the 
ro»f ;  g,  nucleus  globosus. 


Fig.  353. — Diagram  of  Dorsal  and  Ventral  Spino 
Cerebellar  Tracts  entering  Cerebellum  (.Mott). 
P.C.Q.,  posterior  corpora  quadrigeraina;  s.v., 
superior  vermis  of  cerebellum;  d.a.c,  v.a.c, 
dorsal  and  ventral  ascending  cerebellar  tracts. 

cerebellar  tract  (dorsal  spino-cerebcllar  tract)  of  its  own  side  it  carries 
to  the  worm.  These  fibres  occupy  the  outer  portion  of  the  peduncle. 
The  fibres  which  reach  the  restiform  body  from  the  olivary  nucleus  of 
the  opposite,  and  also  in  smaller  numbers  from  that  of  the  same  side, 
run  mainly  to  the  hemisphere.  All  these  fibres  are  afferent  in  relation 
to  the  cerebellum  (cerebcUo-petal).  An  uncrossed  afferent  connection 
also  exists  between  the  cerebellum  and  the  vestibular  branch  of  the 
auditory  nerve,  through  certain  of  its  nuclei  of  reception,  and  also 
between  it  and  the  nuclei  of  other  cranial  nerves,  such  a^  the  trigeminus 
and  the  vagus.  The  fibres  pass  up  in  the  inner  portion  of  the  inferior 
peduncle  (direct  sensory  cerebellar  path  of  Edinger,  Fig.  35  j)  to  the 
nucleus  of  the  roof  (nucleus  tecli)  and  nucleus  globosus.  Some  efferent 
fibres  (cerebellofugal)  also  run  down  from  the  cerebellum  in  the  inferior 
peduncle,  including  fibres  from  the  nucleus  tecti  of  the  opposite  side 
which  are  on  their  way  to  the  medulla  oblongata. 


THE  CENTRAL  NERVOUS  SYSTEM 


The  middle  peduncle  is  in  the  main  a  link  between  the  cerebellar 
cortex  and  the  cerebral  cortex  of  the  opposite  side,  through  the  relay 
of  the  pontine  grey  matter.  Most  of  the  fibres  in  it  are  afferent  in  rela- 
tion to  the  cerebellum,  their  cells  of  origin  being  situated  in  the  nuclei 
of  the  pons,  and  sending  their  axons  across  the  middle  line  to  end  in  the 
cerebellar  cortex. 

The  superior  peduncle  connects  chiefly  the  dentate  nucleus  of  one 
side  with  the  cortex  of  the  opposite  cerebral  hemisphere  through  the 
red  nucleus  of  the  tegmentum  of  the  crus  cerebri  and  the  optic  thalamus 
on  the  opposite  side.  The  great  majority,  or  perhaps  all,  of  its  fibres 
are  efferent  fibres  as  regards  the  cerebellum — i.e.,  their  cells  of  origin  lie 
in  the  dentate  nucleus.     Running  upwards  and  forwards  in  the  superior 

peduncle  towards  the  mid- 
brain they  cross  the  middle 
line  below  the  corpora 
quadrigemina,  and  then 
bifurcate  into  ascending 
and  descending  branches. 
The  ascending  branches  end 
mainly  in  connection  with 
cells  in  the  red  nucleus,  but 
some  of  them  pass  on  to 
the  optic  thalamus,  with 
which  cells  of  the  red 
nucleus  are  also  connected. 
The  thalamus,  as  we  have 
seen,  is  in  its  turn  exten- 
sively connected  with  the 
cerebral  cortex,  and  the 
red  nucleus  (by  the  efferent 
tract  of  Monakow)  with  the 
grey  matter  of  the  cord. 
The  descending  branches 
of  the  fibres  of  the  superior 
peduncle,  entering  the  re- 
ticular formation  of  the 
pons,  pass  down,  it  is  said, 
to  make  connection  with 
the  motor  nuclei  of  the 
cranial  and  spinal  nerves. 
The  tract  of  Gowers,  as 
previously  stated,  comes 
into  relation  with  the  su- 
perior peduncle,  passing 
backwards  along  its  mesial  border  to  the  worm.  Since  the  cortex  of  the 
cerebellum  is  linked  to  the  dentate  nucleus,  the  superior  peduncle  affords 
an  indirect  connection  between  it  and  the  cerebral  cortex.  Through 
the  restiform  body  afferent  impulses  pass  up  to  the  cerebellum.  From 
the  cerebellum  they  may  proceed  to  the  cerebrum.  So  that  the  path  by 
the  restiform  body,  dentate  nucleus,  and  superior  peduncle  may  form  an 
alternative  route  for  afferent  impressions  ascending  from  the  periphery  to 
the  great  brain — a  path  broken  by  at  least  four  relays  of  nerve-cells. 
The  cerebellar  hemisphere  may  be  connected  by  an  efferent  path  through 
the  nucleus  of  Deiters  and  the  descending  antero-lateral  tract  with  the 
motor  roots  of  the  same  side.  Another  efferent  path  (from  the  dentate 
nucleus)  may  be  constituted  by  the  fibres  of  the  superior  peduncle  and 
Monakow's  bundle. 


Fig.  354. — Paths  of  Middle  Cerebellar  Peduacle 
(Mingazzini).  The  scheme  indicates  the  afferent 
and  efferent  paths  which  run  through  the  middle 
cerebellar  peduncle,  connecting  cerebellum  with 
opposite  side  of  cerebrum,  a,  fibre  coming  from 
a  cell  in  the  nuclei  pontis  and  going  to  the  cere- 
bellar cortex;  b,  fibre  from  a  cell  in 'cortex  of 
opposite  cerebral  hemisphere  making  connection 
in  the  pons  with  a  (a  and  b  together  constitute 
an  afferent  path  to  the  cerebellum);  c,  a  fibre 
springing  from  a  Purkinje's  cell  in  the  cerebellar 
cortex  and  making  connection  in  the  pons  with 
a  cell  d,  which  sends  its  axon  to  the  cerebral 
cortex  of  the  opposite  side,  c  and  d  constitute 
an  efferent  path  from  cerebellum  to  opposite 
cerebral  hemisphere;  e,  f,  represent  a  path 
coming  from  the  cerebellar  cortex,  which  crosses 
the  middle  line  in  the  pons,  and  then  ascends 
till  it  loses  itself  in  the  formatio  reticularis. 


FUNCTIONS  OF  CENTRAL  NERVOUS  SYSTEM  859 

We  have  purposely  omitted  to  enumerate  other  paths  by  which 
the  various  tracts  of  grey  matter  in  the  brain  are  brought  into  com- 
munication with  each  other,  and  our  knowledge  of  such  connections 
is  no  doubt  far  from  complete.  When  we  add  that  not  only  are  the 
cerebral  hemispheres  united  by  many  ties  to  the  subordinate  portions 
of  the  cerebro-spinal  axis  and  to  each  other,  but  that  cortical  areas 
of  one  and  the  same  hemisphere  are  in  communication  by  short 
connecting  loops  of  '  association  '  fibres  (Fig.  350),  it  will  be  seen  that 
the  linkage  of  the  various  parts  of  the  central  nervous  system  is 
extremely  complex;  that  an  excitation,  blocked  out  from  one  path, 
may  have  the  choice  of  many  alternative  routes;  and  that  the  ap- 
parent simplicity  and  isolation  of  the  pyramidal  tracts  must  not  be 
allowed  too  far  to  govern  our  views  of  the  possibilities  open  to  a 
nervous  impulse  once  it  has  been  set  going  in  the  labjTinth  of  the 
nervous  network.  Nor  is  it  only  by  the  main  channel  of  the  axis- 
cylinder  that  nervous  impulses  can  be  conducted,  they  can  also  pass 
along  the  collaterals.  And  the  actual  route  taken  by  a  given  impulse 
is  determined  not  only  by  anatomical  relations,  but  also  by  molec- 
ular conditions,  particularly  in  the  terminal  fibrils  of  the  axons, 
collaterals  and  dendrites,  and  in  the  substance,  if  such  a  substance 
there  be,  which  intervenes  between  the  end  arborizations  of  a  neuron 
and  the  dendrites  or  cell-bodies  of  the  neurons  with  which  they  lie  in 
contact.  So  that  a  road  open  at  one  moment  may  be  closed  at 
another.  (See  p.  874.)  We  may  suppose  that  the  greater  the  number 
of  connections  between  the  cells  of  the  central  nervous  system,  the 
greater  is  the  complexity  of  the  processes  w^hich  may  be  carried  on 
within  it.  And,  indeed,  comparison  of  the  brains  of  different  animals 
shows  that  it  is  not  so  much  by  excess  in  the  number  of  nerve-cells 
as  by  the  increased  complexity  of  linkage,  that  a  highly-developed 
brain  differs  from  a  brain  of  lower  type;  the  higher  the  brain,  the 
more  richly  branched  are  the  dendrites  and  the  terminations  of  the 
axons  and  their  collaterals,  and,  therefore,  the  greater  is  the  number 
of  possible  paths  between  one  nerve-cell  and  another. 


Section  VIII. — Functions  of  the  Central  Nervous  System — 
(i)  The  Spinal  Cord  (including  the  Medulla  Oblongata). 

Much  of  our  knowledge  of  the  functions  of  the  central  nervous 
system  and  of  its  divisions  has  been  gained  by  the  removal  or 
destruction  of  more  or  less  extensive  tracts  of  nervous  substance,  or 
the  cutting  off  of  connection  between  one  part  and  another.  But  it 
is  well  to  warn  the  reader  at  the  very  outset  that  in  no  other  part  of 
physiology  is  such  caution  required  in  making  deductions  as  to  the 
working  of  the  intact  mechanism  from  the  phenomena  which  mani- 
fest themselves  after  such  lesions. 


86o  THE  CENTRAL  NERVOUS  SYSTEM 

In  the  first  place,  every  operation  of  any  magnitude  on  the  brain  or 
cord  is  immediately  followed  by  a  depression  of  the  functional  power  of 
the  nervous  tissue  distal  to  the  lesion,  a  depression  which  may  extend 
far  from  the  actual  seat  of  injury  and  manifest  itself  by  various  phe- 
nomena, which  are  grouped  together  under  the  name  of  '  shock,'  better 
termed  spinal  or  cerebro-spinal  shock,  to  distinguish  it  from  the  cardio- 
vascular or  surgical  shock  already  mentioned  (p.  190).  Thus,  when  the 
spinal  cord  of  a  dog  is  divided,  e.g.,  in  the  dorsal  region,  all  power,  all 
vitality,  one  might  almost  say,  seems  to  be  for  ever  gone  from  the 
portion  of  the  body  below  the  level  of  the  section.  The  legs  hang  limp 
and  useless.  Pinching  or  tickling  them  calls  forth  no  reflex  movements. 
The  vaso-motor  tone  is  destroyed,  and  the  vessels  gorged  with  blood. 
The  urine  accumulates,  overfi.lls  the  paralyzed  bladder,  and  continually 
dribbles  away  from  it.  The  sphincter  of  the  anus  has  lost  its  tone,  and 
the  faices  escape  involuntarily.  And  if  we  were  to  continue  our  observa- 
tions only  for  a  short  time,  a  few  hours  or  days,  we  should  be  apt  to 
appraise  at  a  very  low  value  the  functions  of  that  part  of  the  cord 
which  still  remains  in  connection  with  the  paralyzed  extremities.  But 
these  symptoms  are  essentially  temporary.  They  are  the  immediate 
results  of  the  section;  they  are  not  permanent '  deficiency  '  phenomena. 
And  if  we  wait  for  a  time,  we  shall  find  that  this  torpor  of  the  lower 
dorsal  and  lumbar  cord  is  far  from  giving  a  true  picture  of  its  poten- 
tialities; that,  cut  off  as  it  is  from  the  influence  of  the  brain,  it  is  still 
endowed  with  marvellous  powers.  If  we  wait  long  enough,  we  shall 
see  that,  although  voluntary  motion  never  returns,  reflex  movements 
of  the  hind-limbs,  complex  and  co-ordinated  to  a  high  degree,  are  readily 
induced.  A  few  months  after  transection  of  the  cord  it  is  easy  to  show 
that,  although  the  dog  cannot  use  the  hind  limbs  for  continuous  pro- 
gression, the  machinery  for  executing  the  appropriate  movements  exists 
in  the  cord.  When,  for  example,  the  animal  is  held  in  the  proper 
position  and  given  a  slight  push  forwards,  it  may  take  two  or  three  steps 
before  its  legs  give  way.  The  regulation  of  the  movements  necessary 
for  the  maintenance  of  equilibrium  cannot  be  achieved  when  the  control 
of  the  higher  centres  is  eliminated.  In  water,  where  the  problem  of 
the  maintenance  of  the  normal  position  is  solved  by  the  mechanical 
properties  of  the  medium,  the  dog  can  use  the  hind-legs  in  swimming. 
The  tone  of  the  resting  muscles  below  the  lesion  is  even  somewhat 
greater  than  normal.  Vaso-motor  tone  also  comes  back.  The 
functions  of  defaecation  and  micturition  are  normally  performed. 
Erection  of  the  penis  and  ejaculation  of  the  semen  take  place  in  a  dog. 
A  man  with  complete  paralysis  below  the  loins  and  destitute  of  all 
sensation  in  the  paralyzed  region  has  been  known  to  become  a  father 
(Brachet).  Pregnancy  carried  on  to  labour  at  full  term  has  been 
observed  in  a  bitch  whose  cord  was  completely  divided  above  the 
lumbar  enlargement.  The  severity  and  duration  of  spinal  shock  are 
greater  in  the  monkey  than  in  the  dog,  in  man  than  in  the  monkey,  and 
in  the  whole  mammalian  group  than  in  the  lower  vertebrates.  The 
mechanism  of  its  production  has  been  much  discussed,  and  will  be 
referred  to  on  another  page  (p.  884). 

We  cannot  doubt  that  the  spinal  cord  takes  an  important  share  in 
the  recovery  of  function  after  shock.  But  here  again  it  would  be 
erroneous  to  conclude  that  everything  is  due  to  the  cord.  For  Goltz 
and  Ewald  have  been  able  to  keep  dogs  alive  for  long  periods  after 
preliminary  section  of  the  cord  in  the  cervical  region  and  subsequent 
removal  of  large  portions  of  it.  They  find  thq,t  even  after  destruction 
of  the  lumbar  and  sacral  regions  of  the  cord  the  external  sphincter  of 
the  anus,  striped  and  even  voluntary  muscle  though  it  be,  regains  its 


FUNCTIONS  OF  THE  SPINAL  CORD  86i 

tone,  although  it  is  temporarily  lost  after  the  first  cervical  section. 
The  bladder  ultimately  recovers  the  power  of  emptying  itself  spon- 
taneously and  at  regular  intervals.  A  pregnant  bitch  in  which  the 
lumbar  enlargement  and  the  whole  cord  below  it  to  the  cauda  equina 
had  been  removed,  and  therefore  all  the  nerve-roots  supplying  fibres 
to  the  uterus  cut,  whelped  in  a  normal  manner,  and  the  corresponding 
mammary  glands  behaved  exactly  as  the  rest.  Digestion  went  on  as 
usual  when  practically  nothing  of  the  cord  except  its  cervical  portion 
was  left.  Certain  vaso-motor  phenomena  were  also  observed  which 
suggest  that  the  sympathetic  system,  independently  of  the  cerebro- 
spinal system,  is  itself  possessed  of  regulative  powers  (p.  i8i). 

Secondly,  we  must  not  run  into  the  opposite  error,  and  assume, 
without  proof,  that  all  the  functions  which  the  brain  or  cord  is  capable 
of  manifesting  under  abnormal  circumstances  are  actually  exercised  by 
either  when,  under  ordinary  conditions,  it  is  working  along  with  and 
guiding,  or  being  guided  by,  the  other.  For  example,  in  many  animals 
certain  of  the  reflex  powers  of  the  cord  are,  if  not  increased,  at  all  events 
more  freely  exercised  when  the  controlling  influence  of  the  higher  centres 
has  been  cut  off  than  when  the  central  nervous  system  is  intact. 

Thirdly,  there  is  another  class  of  phenomena  which  we  must  make 
allowance  for,  and  perhaps  more  frequently  in  the  case  of  pathological 
lesions  in  man  than  in  experimental  lesions  in  the  lower  animals.  This 
is  the  class  of  '  irritative  '  phenomena.  The  irritation  set  up  by  a  blood- 
clot  or  a  collection  of  pus,  or  in  any  other  way,  in  a  wound  of  the  grey 
or  white  matter,  may  cause  a  stimulation  of  nervous  tracts  by  which, 
for  a  time,  the  '  deficiency  '  effects  of  the  lesion  may  be  masked. 

In  the  fourth  place,  we  must  not  hastily  conclude  that,  when  no 
obvious  deficiency  seems  to  follow  the  removal  of  a  portion  of  the  central 
nervous  system,  the  function  of  that  portion  must  necessarily  be  of 
such  a  nature  as  to  give  rise  to  no  objective  signs.  For  there  is  reason 
to  believe  that,  to  a  certain  extent,  the  function  of  one  part  may,  in  its 
absence,  be  vicariously  performed  by  another. 

Bearing  in  mind  the  cautions  we  have  just  been  emphasizing,  we 
may  broadly  distinguish  between  the  functions  of  the  cord  (including 
the  bulb)  and  those  of  the  brain  proper  by  saying  that  the  cord  is 
essentially  the  seat  of  reflex  actions,  the  brain  the  seat  of  automatic 
actions  and  conscious  processes.  But  neither  of  these  conceptions 
is  entirely  correct.  Both  err  by  defect  and  by  excess.  The  brain, 
it  is. true,  is  pre-eminently  automatic.  The  movements  which  are 
started  in  the  grey  matter  of  the  cerebral  cortex  are  pre-eminently 
voluntary  (p.  915),  but  we  cannot  deny  to  the  brain  the  possession  of 
reflex  powers  as  well.  The  movements  in  which  the  only  nerve 
centres  concerned  are  those  of  the  spinal  cord  are  above  all  reflex 
(p.  86g).  But  some  of  its  centres,  and  especially  those  lying  in  the 
medulla  oblongata — e.g.,  the  respiratory  centre — are,  much  as  they 
are  influenced  by  afferent  impulses,  capable  of  discharging  auto- 
matic impulses  too.  And  while  consciousness  is  certainly  bound  up 
with  integrity  of  the  brain,  and  in  all  the  higher  mammals  is  asso- 
ciated with  cerebral  activity  alone,  it  has  been  plausibly  maintained 
that  the  spinal  cord,  even  of  such  an  animal  as  the  frog,  may  also  be 
endowed  with  something  which  might  be  called  a  kind  of  hushed 
consciousness.     Whether  this  be  so  or  not  for  the  frog,  with  its 


862 


THE  CENTRAL  NERVOUS  SYSTEM 


distinct  though  relatively  ill-developed  cerebral  hemispheres,  it 
would  seem  by  no  means  unlikely  in  the  case  of  fishes  and  animals 
below  them,  which  are  practically  devoid  of  a  cerebral  cortex 
altogether. 

The  functions  of  the  spinal  cord  may  be  classified  thus: 

1.  The  conduction  of  impulses  set  up  elsewhere — either  in  the 

brain  or  at  the  periphery. 

2.  The  modification  of  impulses  set  up  elsewhere  (reflex  action). 

3.  The  origination  of  impulses  (?). 

I  Cerebral 


Ftbr&  for 


DecMSsation 
ofPyramids 


Ti^re  cfDtrect 
pyramidal  tract 

JVerue-Cells^ 
Of  Ant  Horn 


\Uncro5s^d  Tibrt, 


Anterior 

Hoot 

Fibres 


Ant  J/orr) 


Fig-  355- — Some  Possible  Paths  of  Efferent  Impulses  in  the  Central  Nervous  System 
(Schematic).  Details  are  omitted  from  the  scheme.  For  instance,  each  pyra- 
midal fibre  is  represented  as  arborizing  around  one  anterior  cornual  cell  only, 
and  no  collaterals  are  shown.  The  hypothetical  intercalated  neurons  between 
the  pyramidal  fibres  and  the  anterior  horn  cells  (p.  848)  are  not  shown. 

I.  Conduction  of  Nervous  Impulses  by  the  Cord. — The  old  con- 
troversy as  to  whether  the  white  fibres  of  the  spinal  cord  are  directly 
excitable  has  long  been  settled  in  the  affirmative. 

The  inquiry  was  complicated  by  the  presence  of  the  spinal  roots, 
which,  since  the  experiments  of  Charles  Bell,  have  been  known  to  be 
capable  of  excitation  by  artificial  stimuli.  But  at  length  the  dif&culty 
was  overcome  in  this  way:   The  posterior  (dorsal)  portion  of   several 


FUNCTIONS  OF  THE  SPINAL  CORD  863 

segments  of  the  cord  with  the  attached  posterior  roots  and  the  grey 
matter  was  excised.  Long  strands  of  the  white  matter  of  the  anterior 
(ventral)  portion  of  the  cord  were  isolated,  and  laid  on  electrodes,  and 
contractions  of  muscles  were  seen  to  follow  stimulation,  even  when  the 
anterior  roots  nearest  the  stimulating  electrodes  had  been  cut,  and  every 
precaution  taken  to  avoid  escape  of  current  on  to  the  distant  anterior 
roots  of  the  nerves  supplying  the  muscles.  Indeed,  apart  from  direct 
experimental  evidence,  the  fact  that  the  white  fibres  of  the  brain  are 
universally  admitted  to  be  excitable  by  artificial  means  would  be  of 
itself  almost  sufficient  to  decide  the  question,  for  we  know  of  no  essential 
difference  between  the  cerebral  and  the  spinal  fibres.  But  the  con- 
ditions must  rarely  occur  under  which  direct  stimulation  of  white  fibres 
in  their  course  is  possible  in  the  intact  body ;  and  the  only  impulses  with 
which  we  need  concern  ourselves  here  are  those  that  reach  the  con- 
ducting paths  from  grey  matter  in  the  cord  itself  or  in  the  brain,  or  from 
the  peripheral  organs. 

What  sort  of  impulses  do  the  various  tracts  of  the  spinal  cord 
conduct  ?  For  the  dorsal  or  posterior  roots  this  question  was  first 
fully  answered  by  Magendie;  for  the  ventral  or  anterior  roots, 
although  with  a  certain  degree  of  ambiguity,  by  Sir  Charles  Bell. 
Bell  observed  that  when,  in  an  animal  just  killed,  he  mechanically 
stimulated  the  anterior  roots,  muscular  contractions  were  obtained 
at  each  touch  of  the  forceps.  He  concluded  that  the  anterior  roots 
are  motor  and  sensory,  while  the  posterior  roots  are  '  vegetative  ' — 
i.e.,  connected  with  the  functions  of  the  viscera,  the  so-called 
'  vegetative  '  organs.  But  although  he  is  often  credited  with  the 
discovery  of  the  functions  of  the  posterior  roots  as  well,  he  was  not 
the  first  to  make  the  decisive  experiment  necessary  to  show  that  they 
are  the  conductors  of  sensory  impulses.  It  was  after  Magendie's 
discovery  that  only  a  portion  of  the  nerves  are  sensitive,  and  that 
there  are  nerves  '  which  are  like  tendons,  aponeuroses,  or  cartilages 
in  insensibility,'  that  Bell  formulated  the  law  that  the  anterior  roots 
are  purely  motor,  the  posterior  purely  sensory.  This  law,  often 
termed  Bell's  Law,  is  more  correctly  denominated  the  Magendie- 
Bell  Law. 

When  the  posterior  roots  are  divided,  loss  of  sensation  occurs  in 
the  region  to  which  they  are  distributed.  If  onlj^  one  root  is  cut, 
the  loss  of  sensation  is  never  complete  in  any  part  of  the  skin;  and 
Sherrington  has  found  that  the  cutaneous  areas  of  distribution  of 
consecutive  nerve-roots  are  not  perfectly  independent,  but  to  some 
extent  overlap.  Stimulation  of  the  peripheral  end  of  the  divided 
posterior  root  has  no  effect.  Stimulation  of  the  central  end  gives 
rise,  if  the  animal  be  conscious,  to  evidences  of  pain,  and  other  signs 
of  the  passage  of  afferent  impulses — e.g.,  a  rise  in  blood-pressure. 
The  latter  may  also  be  observed  when  the  animal  is  anaesthetized. 

Referred  Pain. — The  posterior  roots  contain  sensory  fibres  not  only 
for  the  skin,  but  also  for  the  deeper  structures  and  the  viscera.  The 
afferent  fibres  reach  the  viscera  by  the  sympathetic,  the  vagus,  and  the 
pelvic  nerves  or  ncrvi  erigentcs.     Clinical  observations  have  thrown 


864  THE  CENTRAL  NERVOUS  SYSTEM 

much  light  upon  the  distribution  of  the  visceral  fibres  and  their  rela- 
tion to  the  cutaneous  sensory  nerves.  It  has  long  been  known  that 
in  disease  of  an  internal  organ  the  pain  is  often  referred  to  some  super- 
ficial part.  It  has  now  been  demonstrated  that  each  organ  is  related 
to  a  more  or  legs  definite  region,  or  more  than  one  region,  of  the  skin. 
In  disease  of  the  organ  there  is  in  this  area  increased  excitability 
(hyperalgesia)  or  tenderness  to  slight  mechanical  stimuli,  and  often 
also  increased  excitability  for  heat  or  cold,  and  the  reflexes  elicited  by 
stimulation  are  exaggerated  (Head,  Dana). 

The  bond  of  connection  appears  to  be  the  origin  from  the  same  spinal 
segments  of  the  autonomic*  sensory  fibres  of  any  viscus  and  the  sensory 
supply  of  the  correspcnding  cutaneous  area.  The  common  anatomical 
origin  seems  to  carry  with  it  a  physiological  correlation,  either  because 
the  irritation  of  the  visceral  fibres  spreads  in  the  cord  to  the  somatic 
afferent  fibres  which  enter  the  corresponding  segments,  or  because  of 
some  action  higher  up  in  the  cerebral  centres,  the  nature  of  which  will 
be  best  considered  along  with  the  general  topic  of  the  localization  of 
sensory  impressions  (Chapter  XVIIL). 

Recurrent  Sensibility. — Although  muscular  contraction  is  the 
most  conspicuous  event  that  follows  stimulation  of  the  peripheral  end 
of  an  anterior  nerve-root,  it  is  by  no  means  the  only  one.  It  is 
frequently  observed,  though  not  in  all  kinds  of  animals,  that  here, 
too,  pain  is  caused.  That  this  pain  is  not  due  to  the  muscular  con- 
traction is  proved  by  the  fact  that  it  can  still  be  elicited  when  the 
nerve-trunk  is  divided  between  the  junction  of  the  roots  and  the 
periphery.  The  real  explanation  of  the  phenomenon  is  that  certain 
fibres  from  the  posterior  roots  ('  recurrent  fibres,'  see  footnote  on 
p.  771)  bend  up  for  some  distance  into  the  anterior  roots,  and  then 
turn  round  again  and  pursue  their  course  to  their  peripheral  dis- 
tribution in  the  mixed  nerve,  or  run  on  in  the  motor  roots  to  supply 
the  sheath  surrounding  them  (nervi  nervorum),  and  even  the  mem- 
branes of  the  spinal  cord. 

The  afferent  impulses  that  enter  the  cord  along  the  posterior  roots 
have  the  choice  of  many  paths  by  which  they  may  reach  the  brain. 
The  following  are  a  few  of  the  routes  which  they  may  follow: 

(i)  They  may  pass  directly  up  through  the  postero-median  column. 
If  they  take  this  route,  their  course  will  be  first  interrupted  by  nerve- 
cells  in  the  gracile  or  cuneate  nuclei  in  the  medulla  oblongata.  Thence 
they  may  find  their  way  across  the  middle  line  by  the  arcuate  fibres  of 
the  upper  or  sensory  decussation,  and,  sweeping  along  the  fillet  and  the 
sensory  path  in  the  hinder  part  of  the  posterior  limb  of  the  internal 
capsule,  finally  arrive  at  the  cerebral  cortex.  Between  the  gracile  and 
cuneate  nuclei  and  the  cortex  they  pass  through  nerve-cells  in  the  optic 
thalamus. 

(2)  They  may  pass  up  by  the  direct  cerebellar  tract  and  restiform 
body  to  the  grey  matter  of  the  cerebellar  worm.  If  they  take  this 
route  their  course  will  be  interrupted  very  soon  after  their  entrance  into 

*  Langley  uses  the  term  autonomic  nervous  system  to  include  the  nerve 
supply  of  heart  muscle,  all  unstriated  muscle,  and  all  gland  cells  in  the  body. 
It  embraces,  in  addition  to  the  sympathetic,  cranial  autonomic  fibres  in 
several  of  the  cranial  nerves  and  sacral  autonomic  fibres  in  the  nervi  erigent«s 
(see  Chapter  XVII.). 


FUNCTIONS  OF  THE  SPINAL  CORD  863 

the  cord  in  the  cells  of  Clarke's  column.  Since  the  superficial  grey 
matter  of  the  vermis  is  connected  by  association  fil^res  with  the  dentate 
nucleus,  and  the  dentate  nucleus  by  the  superior  peduncle  with  the  oppo- 
site cerebral  hemisphere,  this  is  also  a  possible  path  to  the  great  brain. 

(3)  They  may  reach  the  antero-lateral  ascending  tract  of  the  same 
side  through  its  cells  of  origin  in  the  spinal  grey  matter,  and,  passing 
through  the  medulla  and  pons  to  the  superior  peduncle  of  the  cere- 
bellum, enter  the  grey  matter  of  the  superior  worm. 

(4)  They  may  cross  the  middle  line,  after  entering  the  cord,  through 
axons  or  collaterals  (p.  844)  which  run  in  the  anterior  and  also  in  the 
posterior  commissure,  enter  one  of  the  ascending  tracts  on  the  other 
side — e.g.,  the  tract  of  Gowers — and  continue  without  further  decus- 
sation up  to  their  central  destination. 

(5)  They  may  spread  from  neuron  to  neuron  in  the  tangle  of  the  grey 
matter  itself,  and  pass  out  again  at  a  different  level  into  one  of  the 
white  tracts  on  the  same  or  on  the  opposite  side  of  the  cord. 

Efferent  impulses  from  the  brain  may  travel — 

(i)  Through  the  direct  or  crossed  pyramidal  tract. 

(2)  From  one  side  of  the  cerebral  cortex  to  the  other,  and  then  down 
the  pyramidal  tracts  corresponding  to  that  side  (?). 

(3)  From  the  frontal  part  of  the  cerebral  cortex,  through  the  anterior 
limb  of  the  internal  capsule  to  the  grey  matter  in  the  pons,  and  thence 
to  the  cerebellum  by  its  middle  peduncle. 

(4)  From  the  occipital  or  temporal  cortex,  in  the  hinder  rim  of  the 
internal  capsule,  to  the  pontine  grey  matter,  and  through  the  middle 
peduncle  to  the  cerebellum.  From  the  cerebellum  they  may  possibly 
pass  down  to  the  nucleus  of  Deiters  and  thence  along  the  antero-lateral 
descending  tract  to  the  anterior  horn  of  the  cord,  and  indirectly  to  the 
periphery. 

All  the  paths  enumerated,  as  well  as  others  to  which  it  would  be 
tedious  to  formally  refer,  and  which  the  ingenuity  of  the  reader  may 
profitably  be  employed  in  constructing  for  himself,  from  the  data 
already  given,  are  to  be  looked  upon  as  possible  channels  for  the 
passage  of  impulses  between  the  brain  and  the  periphery.  But  it 
must  be  distinctly  pointed  out  that  what  is  certain  is  in  this  case 
much  more  limited  than  what  is  possible.  Among  the  efferent  paths 
it  is  certain  that  the  pyramidal  tracts  are  conductors  of  voluntary 
motor  impulses,  and  that  in  most  individuals  the  great  majority  of 
such  impulses  decussate  in  the  medulla  oblongata,  only  a  small 
minority  in  the  cord.  For  a  lesion  involving  the  pyramidal  tract 
above  the  decussation  of  the  pyramids  causes  paralysis  of  the  oppo- 
site side  of  the  body,  a  lesion  below  the  decussation  paralysis  of  the 
same  side.  It  is  certain  that  when  one  pyramidal  tract  has  been 
destroyed,  in  many  animals  at  least,  the  resulting  paralysis  is  soon 
recovered  from,  at  any  rate  to  a  great  extent,  and  it  is  possible  that 
in  this  case  the  motor  cortex  on  the  side  of  the  lesion  has  placed  itself 
again  in  communication  with  the  p.iralyzed  muscles  through  its 
commissural  connections  with  the  ojjposite  hemisphere.  This, 
however,  is  not  the  only  alternative,  for,  as  already  pointed  out,  the 
pyramidal  tracts  arc  not  the  only  cortico-spinal  paths  which  can 

55 


866  THE  CENTRAL  NERVOUS  SYSTEM 

subserve  volitional  movements,  and  division  of  the  anterior  portion 
of  the  antero-lateral  column  may  cause  deeper  and  more  permanent 
paralysis  than  division  of  the  pyramidal  tract. 

In  the  dog  total  section  of  the  pyramids  is  not  followed  by  com- 
plete paralysis  of  voluntary  movements,  and  stimulation  of  the 
cortical  motor  areas  can  still  elicit  characteristic  movements.  It  is 
obvious  that  impulses  emanating  from  the  cortex  can  reach  the 
motor  nuclei  of  the  cord  by  other  routes  than  the  long  pyramidal 
fibres,  possibly  by  paths  with  several  segments,  of  which,  for 
example,  the  rubro-spinal  tract  (p.  839)  may  be  one.  Just  as  an 
important  business  house  may  find  it  useful  or  indispensable  to 
supplement  or  replace  the  common  telegraph  service  by  private  wires 
in  the  interest  of  more  prompt  and  satisfactory  communication  with 
its  principal  correspondents,  while  still  utihzing  the  ordinary  channels 
to  some  extent,  so  the  higher  brains  may  be  supposed  to  have 
developed  more  and  more  the  direct  service  of  the  pyramidal  tract 
to  tighten  the  grip  of  the  cortex  upon  the  motor  nuclei  of  the  cerebro- 
spinal axis,  while  still  availing  themselves,  although  in  diminishing 
degree  as  their  evolution  proceeds,  of  the  more  primitive  indirect 
paths. 

Decussation  of  the  Sensory  Paths. — On  the  other  hand,  it  is  certain 
that  pathological  or  traumatic  lesions,  apparently  involving  the 
destruction  of  one  lateral  half  of  the  cord  in  man  and  experimental 
oemisections  in  some  mammals,  are  followed  by  symptoms  which 
suggest  that  some  kinds  of  sensory  impulses  decussate  chiefly  in  the 
spinal  cord — viz.,  diminution  or  loss  of  sensibility  to  pain  and  to 
changes  of  temperature  on  the  opposite  side  below  the  level  of  the 
lesion,  with  little  or  no  impairment,  and  often  increase  of  sensibility 
(hyperaesthesia)  on  the  same  side.  Tactile  sensibility  is  lost  on  the 
side  of  the  lesion,  and  likewise  the  muscular  sense. 

The  first  general  description  of  this  symptom-complex  was  given  by 
Brown-Sequard.  On  the  basis  of  clinical  observations  in  man,  he 
came  to  the  conclusion  that  unilateral  lesions  of  the  cord,  equivalent 
approximately  to  a  semisection,  are  associated  with  muscular  paralysis 
below  the  level  of  the  lesion  on  the  same  side,  and  loss  of  cutaneous 
sensibility  on  the  opposite  side,  while  on  the  side  of  the  lesions  there 
may  be  an  augmentation  of  sensibility.  He  interpreted  these  facts  as 
meaning  that  the  sensory  path  decussates  soon  after  its  entrance  into 
the  cord.  The  sensory  path  from  the  left  side  is  therefore  spared  by  a 
lesion  of  the  left  side  of  the  cord,  but  interrupted  by  a  lesion  of  the 
right  side  of  the  cord.  The  left  and  right  motor  paths,  having  already 
decussated  in  the  bulb,  are  cut  by  lesions  in  the  left  and  right  halves  of 
the  cord  respectively.  I-ong  afterwards  Brown-Scquard  saw  cause  to 
retract  this  interpretation  of  the  facts  observed  by  him,  but  the  majority 
of  subsequent  observers  have  considered  his  original  hypothesis  more 
satisfactory  than  his  later  ones.  While  it  may  be  true  that  in  man  it  has 
not  been  rigidly  demonstrated  that  the  symptoms  are  associated  with 
a  clean-out  lesion  precisely  limited  to  one-half  of  the  cord,  clinical 
observation  has  on  the  whole  tended   to  confirm  the  view  that  an 


FUNCTIONS  OF  THE  SPINAL  CORD  867 

important  portion  of  the  sensory  path  decussates  in  the  cord.  But  it 
is  a  curious  circumstance  that  experimental  physiologists  have  for  the 
most  part  obtained  contradictory  results.  Thus  Mott,  working  with 
monkeys,  found  that  the  different  kinds  of  sensation,  far  from  being 
abolished,  are  as  a  rule  impaired  in  a  smaller  degree  on  the  side  opposite 
to  the  semisection  than  on  the  same  side,  while  Fcrrier  and  Turner 
obtained  on  the  whole  a  contrary  result,  and  one  that  corresponded 
closely  with  Brown-Sequard's  original  description.  The  discovery  that 
no  ascending  degeneration,  or  only  a  trifling  amount,  is  to  be  found  on 
the  opposite  side  of  the  cord,  either  after  semisection  or  after  division 
of  posterior  roots,  does  not  of  itself  enable  us  to  decide  the  question. 
For  while  this  latter  fact  shows  that  few  or  none  of  the  afferent  fibres 
cross  the  middle  line  to  enter  the  long  conducting  paths  before  being 
interrupted  by  nerve-cells,  it  by  no  means  proves  that  afferent  impulses 
do  not  decussate  in  the  cord.  The  long  paths  of  the  posterior  column, 
indeed,  do  not  decussate  below  the  level  of  the  bulb.  The  dorsal  and 
ventral  spino-cerebellar  tracts  are  also,  in  the  main  at  least,  uncrossed 
spinal  paths.  A  portion  of  the  afferent  impulses  must  therefore  be 
carried  up  to  the  cerebrum  and  the  cerebellum  without  decussating  in 
the  cord.  But  nobody  can  tell  how  massive  a  hnk  between  the  two 
halves  of  the  cord  may  be  formed  by  the  grey  matter  and  the  endogenous 
fibres  of  the  white  columns  and  their  collaterals.  We  know  that  some 
afferent  impulses  do  decussate  far  below  the  level  of  the  medulla.  For, 
(i)  A  part  of  the  action  current  (p.  8io)  crosses  the  middle  line  and 
ascends  in  the  opposite  half  of  the  cord  when  the  central  end  of  one 
sciatic  is  stimulated  (Cotch  and  Horsley).  (2)  Crossed  reflex  move- 
ments are  possible;  and  when  excitation  of  the  central  end  of  the  sciatic 
is  followed  by  contraction  of  the  muscles  of  the  opposite  fore-limb,  the 
afferent  impulses  must  either  decussate  in  the  lumbar  cord,  and  then 
run  up  on  the  opposite  side  to  the  level  of  the  brachial  plexus,  or  must 
ascend  on  the  same  side  and  cross  over  somewhere  between  the  plane 
of  the  sciatic  and  the  brachial  nerve-roots.  The  only  other  hypothesis 
on  which  crossed  reflex  action  can  be  explained — but  a  hypothesis  for 
which  there  is  not  a  tittle  of  evidence — is  that  the  afferent  impulse 
always  acts  on  the  few  motor  cells  whose  axis-cylinder  processes  pass 
over  to  the  opposite  side,  and  there  enter  anterior  nerve-roots.  But 
while,  for  these  reasons,  it  cannot  be  denied  that  some  afferent  impulses 
decussate  in  the  cord,  it  would  be  an  error  to  conclude  that  all  do  so  in 
any  animal,  or  that  all  animals  are  in  this  respect  alike.  It  is  indeed 
extremely  probable  that  in  different  species  of  animals,  and  even  in 
individuals  of  the  same  species,  there  are  considerable  differences  in 
the  extent  of  the  sensory  decussation  in  the  cord,  just  as  there  arc  in  the 
extent  of  the  motor  decussation  in  the  bulb.  In  some  animals  the 
greater  part  of  the  sensory  path  may  decussate  in  the  cord ;  in  others  the 
greater  pait  may  decussate  in  the  bulb,  or  higher  up.  The  lack  of 
agreement  in  the  experimental  results  may  be  due  partly  to  this  cause. 
When  it  is  further  remembered  how  diflicult  it  sometimes  is  to  interpret 
the  account  which  a  man  gives  of  his  sensations,  and  to  recognize 
precisely  the  degree  and  nature  of  sensory  defects  produced  by  disease 
in  the  human  subject,  it  will  not  be  thought  surprising  that  experi- 
ments on  animals,  from  the  time  of  Galen  onwards,  should  have  yielded 
evidence  which,  although  perhaps  now  at  length  tending  to  a  definite 
result,  is  still  unfinished  and  in  part  conflicting. 

If,  leaving  them  out  of  account,  not  as  valueless  but  as  still 
difficult  of  interpretation,  we  attempt  to  draw  any  general  conclusion 


868  THE  CENTRAL  NERVOUS  SYSTEM 

from  the  clinical  observations  which,  however  imperfect,  are  in  such 
questions  our  surest  guide,  it  can  only  be  this,  that  in  man  some 
of  the  sensory  impulses,  and  particularly  those  connected  with  the 
cutaneous  sensations  of  pain  and  temperature,  decussate,  in  part  at 
least,  in  the  cord.  But  there  is  also  evidence  that  tactile  afferent  im- 
pulses, including  those  coming  from  the  muscles  and  related  to  the 
muscular  sense,  and,  it  may  he,  some  of  the  impulses  associated  with 
pain,  decussate,  not  in  the  cord,  hut  in  the  hulh. 

The  Paths  for  Different  Kinds  of  Sensory  Impressions. — If  this  is  the 
state  of  our  knowledge  where  tlie  problem  is  merely  to  determine  the 
crossing-place  of  afferent  impulses  which  are  certainly  known  to  cross, 
it  is  only  to  be  expected  that  we  should  be  still  more  in  the  dark  as 
regards  the  routes  by  which  different  kinds  of  afferent  impulses  thread 
their  way  through  the  maze  of  conducting  paths  in  the  neural  axis  to 
reach  their  planes  of  decussation  and  gain  the  '  sensory  crossway  '  in 
the  internal  capsule.  Some  authors  have  indeed  cut  the  Gordian  knot 
by  assuming  that  any  kind  of  sensory  impression  may  travel  up  any 
afferent  path.  Direct  stimulation  of  a  naked  nerve-trunk,  it  has  been 
argued  in  favour  of  this  view,  gives  rise  to  a  sensation  of  pain;  stimula- 
tion of  the  skin  in  which  the  end-organs  of  the  nerve  lie  gives  rise  to  a 
sensation  of  touch  or  a  sensation  of  temperature,  according  as  the 
stimulus  is  a  mild  mechanical  or  a  thermal  one,  the  contact  of  a  feather 
or  of  a  hot  test-tube.  Why,  it  has  been  asked,  should  we  imagine  that 
the  difference  in  the  result  of  stimulation  depends  on  a  difference  in  the 
nerve-fibres  excited,  and  not  on  a  difference  in  the  kind  of  impulses  set 
up  in  the  same  nerve-fibres  ?  This  is  a  question  which  we  shall  have 
again  to  discuss.  But  apropos  of  our  present  problem,  we  may 
say  that  there  is  very  clear  proof  from  the  pathological  side  that  a 
limited  lesion  in  the  conducting  paths  of  the  central  nervous  system 
may  be  associated  with  defect  or  total  loss  of  one  kind  of  sensation,  while 
all  the  other  kinds  remain  intact.  And  there  seems  no  other  tenable 
hypothesis  than  that  in  such  cases  the  pathological  change  has  picked 
out  a  particular  group  of  fibres,  either  collected  into  a  single  strand  or 
scattered  among  unaltered  fibres  of  different  function.  For  example, 
in  syringo-myelia,  a  condition  in  which  cavities  are  formed  in  the  grey 
matter  of  the  cord  secondary  to  a  new  growth  of  the  neuroglia  surround- 
ing the  central  canal,  a  frequent  symptom  is  the  loss  in  a  certain  region 
of  sensibility  to  pain  and  to  changes  of  temperature,  while  tactile 
sensibility  is  unaffected  (dissociation  of  sensations).  Again,  in  loco- 
motor ataxia,  a  disease  in  which  inco-ordination  of  movement  and 
derangement  of  the  mechanism  of  equilibration  are  prominent  symptoms, 
degeneration  in  the  posterior  column  of  the  cord  is  a  most  constant 
lesion.  And  there  is  strong  evidence  that  afferent  impulses  from 
muscles  and  tendons,  which  either  give  rise  to  impressions  belonging  to 
the  group  of  tactile  sensations,  or  produce  no  effect  in  consciousness,  and 
which,  according  to  the  most  widely  accepted  doctrine,  serve  as  the 
basis  of  the  muscular  sense,  and  play  an  important  part  in  the  main- 
tenance of  equilibrium  (p.  910),  pass  up  in  the  posterior  column.  It 
may  also  conduct  tactile  impressions  from  the  skin.  A  case  has  been 
observed  where  a  man  received  a  stab  which  divided  the  whole  of  one 
side  of  the  cord  and  the  posterior  column  of  the  other  side.  Sensibility 
to  touch  was  lost  on  both  sides  of  the  body  below  the  level  of  the  injury, 
sensibility  to  pain  only  on  the  side  opposite  to  the  main  lesion.  In 
another  case,  in  which  some  small  syphilitic  tumours  (gummata)  in 


FUNCTIONS  OF  THE  SPINAL  CORD  869 

the  lateral  column  on  the  left  side  caused  marked  degeneration  in  the 
left  direct  cerebellar  tract,  the  tract  of  Gowers,  and  the  crossed  pyram- 
idal tract,  without  affecting  the  posterior  columns,  tactile  sensibility 
was  only  slightly  impaired  in  the  opposite  leg,  while  the  sensibility  for 
pain  and  temperature  was  much  enfeebled.  In  the  left  leg,  which  was 
paralyzed,  there  was  slight  hypera;sthesia.  These  observations  indicate 
that  impressions  of  pain  and  temperature  pass  up  in  the  antero-lateral 
column,  cither  in  the  tract  of  Gowers,  or  in  the  direct  cerebellar  tract,  or 
in  both  (Dejerine  and  Thomas). 

But  it  does  not  follow  that  they  cannot  ascend  by  other  patlis  as 
well.  It  appears,  indeed,  that  the  grey  matter  of  the  cord,  or,  rather, 
short  endogenous  fibres  arranged  in  series  in  the  antero-lateral  column 
so  as  to  connect  the  grey  matter  at  different  levels,  constitute  such  a 
path,  and  that  impulses  which  give  rise  to  pain  can  be  propagated  along 
a  cord  in  wliich  hardly  a  vestige  of  white  substance  remains  uncut.  In 
man  the  path  for  pain  and  temperature  impressions  along  these  short 
endogenous  fibres  seems  to  be  mainly  or  entirely  a  crossed  path.  1  lie 
afferent  paths  for  such  vaso-motor  reflexes  as  are  elicited  by  stimulation 
of  the  central  end  of  the  sciatic  ascend  in  the  lateral  column,  and  the 
impulses  largely  cross  the  middle  line  in  the  cord.  The  posterior 
columns  have  nothing  to  do  with  the  conduction  of  painful  impressions, 
for  division  of  them  causes  not  anaesthesia,  but  rather  hyperajsthesia, 
while  if  they  are  left  intact,  and  the  rest  of  the  cord,  including  the  grey 
matter,  divided,  the  animal  is  insensitive  to  pain  below  the  level  of  the 
lesion.  Just  as  man  differs  from  lower  animals  in  the  completeness 
with  which  certain  of  the  sensory  impressions  decussate  in  the  cord,  so 
differences  exist  in  the  degree  of  localization  of  the  different  kinds  of 
impressions  in  particular  tracts.  One  of  the  outstanding  differences  is 
that  in  animals  it  seems  to  be  easier  for  a  still  intact  path  to  be  substi- 
tuted for  a  severed  path  as  a  conductor  of  impulses  which  normally 
traverse  the  latter.  The  rapidity  with  which  sensation  is  restored 
below  the  lesion  after  semisection  of  the  cord  in  animals  is  an  illustration 
of  this.  Another  difference,  which  can  be  explained  in  the  same  way,  is 
that  a  sharply-marked  dissociation  of  sensations — retention  of  tactile 
sensibility,  for  example,  with  loss  of  sensibility  to  pain  or  to  pain  and 
temperature  changes — either  cannot  be  produced  experimentally  in 
animals,  or  is  very  difficult  to  realize. 

The  impulses  which  descend  the  cord  give  token  of  their  arrival  at  the 
periphery  by  causing  cither  contraction  of  voluntary  muscles,  or  con- 
traction of  the  smooth  muscular  fibres  of  arteries,  or  secretion  in  glands. 
They  all  pass  down  in  tlie  antero-lateral  column,  but  the  path  of  the 
voluntary  impulses  in  the  pyramidal  tracts  is  the  best  known  and  most 
shari:)ly  defined. 

2.  Modification  of  Impulses  set  up  elsewhere  (Reflex  Action). — 
The  spinal  cord,  although  it  is  a  conductor  of  nervous  impulses 
originating  elsewhere,  is  by  no  means  a  mere  conductor.  Many  of 
the  impulses  which  fall  into  the  cord  are  intemipted  in  its  grey 
matter.  Some  of  the  efferent  impulses  proceeding  from  the  brain 
are  perhaps  modified  in  thecord.and  thentransmitted  to  the  muscles. 
Some  of  the  afferent  impulses  are  modified,  and  then  transmitted  to 
the  brain ;  someare  modified,  and  deflected  altogotherintoaneflerent 
path.  These  last  are  the  impulses  which  give  rise  to  reflex  effects. 
A  reflex  action  has  sometimes  been  defined  as  an  action  carried  out 
in  the  absence  of  consciousness;  not  necessarily,  however,  in  the 


870  THE  CENTRAL  NERVOUS  SYSTEM 

absence  of  general  consciousness,  but  in  the  absence  of  consciousness 
of  the  particular  act  itself.  But  the  term  is  now  more  correctly 
used  so  as  to  embrace  all  kinds  of  actions  which  are  not  directly 
voluntary,  whether  the  individual  is  conscious  of  them  or  not.  For 
example,  when  the  sole  of  rhe  foot  is  tickled,  the  leg  is  irresistibly 
and  involuntarily  drawn  up  by  reflex  contraction  of  its  muscles ;  yet 
the  person  is  perfectly  cognizant  both  of  the  movement  and  of  the 
sensation  which  accompanies  the  afferent  impulse.  Many  reflex 
actions  usually  associated  with  sensations  proceed  normally  when 
consciousness  is  entirely  in  abeyance;  during  sleep  most  of  the 
ordinary  reflexes  can  be  elicited. 

Anatomical  Basis  of  Reflex  Action. — Since  the  essence  of  reflex  action 
is  that  the  arrival  of  afferent  impulses  in  the  spinal  cord  or  brain  causes 
the  discharge  of  efferent  impulses,  there  must  be  some  connection 
between  the  incoming  and  the  outgoing  nerve-fibres.  In  unicellular 
animals,  such  as  amoeba,  there  is  no  differentiation  of  any  special 
nervous  or  conducting  path.  A  stimulus  applied  at  one  point  may 
cause  contraction  anywhere.  Even  in  the  lowest  multicellular  animals 
or  metazoa — e.g.,  in  the  sponges — there  is  no  special  nervous  tissue. 
In  some  species  of  hydra,  however,  many  of  the  surface  or  ectodermic 
cells  (p.  6)  possess  deeply-placed  contractile  or  muscular  processes, 
and  stimulation  of  the  surface  cells  is  followed  by  contraction  of  these 
processes.  We  may  imagine  that  the  first  beginnings  of  an  actual 
nervous  sj^stem  may  have  arisen  by  a  further  differentiation  of  such 
an  ectodermic  cell  into  a  receptive  portion  at  the  surface,  a  deeper  con- 
tractile portion,  and  an  intermediate  strand  of  protoplasm  connecting 
the  two,  and  capable  of  conducting  the  excitation  from  surface  to 
muscular  process.  In  such  a  reflex  arc  the  nervous  link  would  consist 
only  of  the  conducting  strand  analogous  to  the  nerve  fibre  joining  the 
receptive  or  sensory  element  to  the  contractile  element,  and  the  dis- 
tinction between  afferent  and  efferent  fibre  would  not  exist.  When 
development  has  gone  a  step  further,  and  the  neuro-muscular  process 
is  interrupted  by  a  second  epithelial  cell  transformed  into  a  nerve-cell, 
the  afferent  fibre  enters  one  pole  and  the  efferent  fibre  leaves  the  other 
pole  of  the  same  cell.  It  is  this  condition  which  we  actually  find  when 
the  nervous  system  first  emerges  in  the  animal  scale  as  an  unmistakably 
differentiated  structure — namely,  in  the  Ccelenterates  in  such  forms  as 
the  jellyfishes.  Here  the  three  types  of  cell,  receptive  or  sensory  cell, 
reactive  or  central  cell,  and  motor  or  contractile  cell,  are  connected 
together  by  conducting  paths  or  nerve-fibres.  In  a  simple  reflex  action 
three  events  can  be  distinguished :  stimulation  of  a  receiving  mechanism, 
conduction  of  the  excitation,  and  the  consequent  reaction  or  end-effect. 
The  receiving  mechanism  or  receptor  may  consist  of  ordinary  sensory 
nerve-endings  in  the  skin,  or  of  special  sense-endings,  as  in  the  retina 
or  internal  ear.  The  conducting  mechanism  or  conductor  in  all  except 
the  very  simplest  nervous  systems  is  made  up  of  at  least  two  neurons, 
one  the  afferent  portion  of  the  reflex  arc  connected  with  the  receptor, 
the  other  the  efferent  portion  of  the  arc,  connected  with  the  organ, 
sometimes  termed  the  effector  organ — a  muscle,  e.g.,  or  a  gland — which 
accomplishes  the  end-effect.  The  transference  of  the  excitation  from 
the  afferent  to  the  efferent  neuron  takes  place  across  the  intervening 
synapse.  The  simple  isolated  reflex  arc,  as  thus  described,  although 
a  convenient  abstraction,  corresponds  but  little  to  anything  which 
actu  dly  exists  in  one  of   the  higher  animals.     With  increasing  com- 


FUNCTIONS  OF  THE  SPINAL  CORD  871 

plexity  of  organization  the  nervous  impulse  passing  up  an  afferent 
fibre  is  in  general  offered,  instead  of  a  single  efferent  path,  a  choice  of 
many  potential  routes  when  it  reaches  the  spinal  cord.  We  have 
previously  (p.  844)  described  the  course  taken  by  the  fibres  of  the 
posterior  roots  on  entering  the  cord.  It  is  obvious  that  through  the 
main  fibres  and  their  collaterals  an  extensive  connection — partly  direct, 
partly  by  the  link  of  intermediate  neurons — is  established  with  the 
motor  cells  on  both  sides  of  the  cord.  But  the  facts  of  pliysiology 
demonstrate  an  even  ampler  connection  than  the  mere  anatomical 
study  of  the  distribution  of  the  root-fibres  would  suggest.  Indeed,  the 
phenomena  of  strychnine-poisoning  seem  to  show  that  every  afferent 
fibre  is  potentially  connected  with  the  motor  mechanisms  of  the  whole 
cord,  or  at  least  with  a  very  large  proportion  of  them.  For  in  a  frog  under 
the  influence  of  this  drug,  stimulation  of  the  smallest  portion  of  the  skin 
will  cause  violent  and  general  convulsions,  which  are  unaffected  by  de- 
struction of  the  brain,  but  cease  at  once  on  destruction  of  the  cord  (p.  876). 

In  an  unpoisoned  reflex  frog — that  is,  a  frog  in  which  interference 
with  the  single  spinal  reflexes  has  been  prevented  by  section  of  the  bulb 
or  destruction  of  the  brain — the  movements  resulting  from  stimulation 
of  a  given  receptive  area  are  by  contrast  surprisingly  limited,  localized, 
and  constant.  Thus,  a  harmful  stimulus  of  a  certain  intensity  applied 
to  a  toe  will  elicit  time  after  time  a  raising  of  the  leg — in  other  words, 
an  excitation  of  muscles  whose  motor  nerves  arise  from  cells  in  the  same 
region  of  the  cord  into  which  the  afferent  fibres  from  the  receptive  skin 
area  enter.  The  localization  of  the  reflex  is  in  this  case  without  doubt 
dependent  upon  the  fact  that  the  connections  of  the  afferent  fibres  with 
the  group  of  efferent  neurons  in  question  are  more  direct  and  more 
intimate  than  with  any  other  group.  This  anatomical  isolation  of  a 
given  reflex  arc  is  never  complete,  but  so  far  as  it  goes  it  may  be 
assumed  to  be  constant  and  incapable  of  variation.  Under  normal 
conditions  the  anatomical  isolation  is  always  supplemented  by  a 
physiological  isolation,  which  is  susceptible  of  variation  in  the  direction 
either  of  increase  or  of  diminution. 

It  is  therefore  a  question  of  great  interest  how  the  isolated  con- 
duction of  the  impulses  in  a  given  reflex  arc,  in  so  far  as  it  depends  upon 
the  physiological  condition  of  the  arc  and  of  its  connections,  is  normally 
achieved.  The  best  answer  which  can  at  present  be  given  is  that  it  is 
not  equally  easy  for  a  reflex  excitation  to  pass  across  all  the  synapses 
which  are  potentially  open  to  it,  and  that  a  lowering  of  the  resistance 
of  the  synapses  in  the  favoured  path  is  probably  quite  as  important  a 
factor  in  the  isolation  as  an  increase  of  the  resistance  in  those  which 
are  to  be  barred.  Following  the  path  of  least  resistance,  the  excitation 
traverses  the  synapse  or  synapses  which  it  is  easiest  for  it  to  break 
through.  What  property  of  the  synapse  is  associated  with  resistance 
to  the  passage  of  the  impul.se  is  unknown.  But  it  is  a  variable  property, 
and  when  a  general  reduction  in  the  resistance  is  produced,  as  by  strych- 
nine or  tetanus  toxin,  an  excitation  impressed  upon  a  single  afferent 
path  may  force  a  great  many  synapses  normally  impervious  to  it. 

While  it  is  convenient  in  a  preliminary  survey  to  speak  of  the  resist- 
ance to  spreading  of  the  excitation  in  the  conl  being  iliminished  by 
stryclinine  or  by  tetanus  toxin,  we  shall  see  presently  that  more  than 
this  is  involved  (p.  875). 

Principle  of  the  Common  Path. — In  considering  the  architecture 
of  the  cerebro-spinal  nervous  system  as  a  basis  of  reflex  action,  one 
feature  is  of  such  importance  as  to  deserve  special  mention.     The 


872  THE  CENTRAL  NERVOUS  SYSTEM 

afferent  neurons,  running  from  the  receptive  surfaces  to  the  centres, 
constitute  each  for  its  own  receptive  point  a  '  private  '  path  which 
can  only  be  used  by  impulses  arising  at  that  point,  and  not  by 
impulses  arising  at  any  other  point.  Through  its  central  connec- 
tions an  afferent  neuron  from  a  single  point  may  be  put  into  com- 
munication with  numerous  efferent  neurons,  and  thus  with  numerous 
and  distant  effector  organs  (muscles  or  glands).  Conversely,  the 
efferent  portion  of  a  single  reflex  arc  can  convey  reflex  excitations 
originating  in  numerous  and  distant  receptive  fields.  It  is  the  sole 
path  which  all  efferent  impulses — let  them  originate  where  they  may 
— must  use  to  reach  the  end-organ  in  question.  It  is  tnerefore  not  a 
private  but  a  public  path,  and  may  be  termed  in  this  relation  the 
final  common  path  (Sherrington). 

The  existence  of  the  common  path  is  of  great  importance  in  under- 
standing the  manner  in  which  reflexes  are  compounded  together,  a 
problem  absolutely  fundamental  in  nervous  co-ordination.  One 
consequence  of  the  existence  of  a  common  path  is  that  when,  among 
the  receptors  which  may  use  it,  two  are  simultaneously  stimulated 
which,  when  separately  excited,  produce  opposite  effects  upon  the 
effector  organ,  only  one  of  the  effects  is  produced.  In  other  words, 
impulses  which  produce  the  two  opposed  effects  can  be  successively, 
but  cannot  be  simultaneously,  sent  along  the  common  path.  Thus, 
'  excitation  of  the  central  end  of  the  afferent  root  of  the  eighth  or 
seventh  cervical  nerve  of  the  monkey  evokes  reflexly  in  the  same 
individual  animal  sometimes  flexion  at  the  elbow,  sometimes  ex- 
tension. If  the  excitation  be  preceded  by  excitation  of  the  first 
thoracic  root,  the  result  is  usually  extension;  if  by  excitation  of  the 
sixth  cervical  root,  it  is  usually  flexion.  Yet  though  the  same  root 
may  thus  be  made  to  evoke  reflex  contraction  of  the  flexors  or  of  the 
extensors,  it  does  not  evoke  contraction  in  both  flexors  and  extensors 
in  the  same  reflex  response.  .  .  .  The  flexor-reflex,  when  it  occurs, 
seems,  therefore,  to  exclude  the  extensor-reflex,  and  vice  versa. 
Either  the  one  or  the  other  results,  but  not  the  two  together ' 
(Sherrington).  It  is  obvious  that  this  is  an  advantageous  arrange- 
ment. An  algebraical  summation  of  the  opposed  effects  by  the 
common  path  would  result  in  a  useless  action  which  was  neither 
effective  flexion  nor  effective  extension,  a  compromise  and  not  a 
co-ordination.  The  conditions  which  determine  which  of  two  or 
more  competing  reflexes  shall  obtain  possession  of  the  final  common 
path  are  considered  on  p.  874. 

Role  of  the  Receptor  in  Reflex  Action. — The  r61e  of  the  receptor  in 
the  reflex  arc  is  above  all  to  sift  out  from  the  various  kindsof  im- 
pressions impinging  upon  the  receiving  surface  the  particular  kind 
to  which  the  appropriate  response  is  the  reflex  action  in  question. 
As  will  be  pointed  out  in  greater  detail  in  the  study  of  the  special 
senses,  each  kind  of  afferent  end-organ  has  become  adapted  to  a 


FUNCTIONS  OF  THE  SPINAL  CORD  873 

special,  or,  as  it  is  termed,  an  '  adequate  '  stimulus,  so  that  it  is 
easily  affected  by  this,  and  with  difficulty  or  not  at  all  by  other 
modes  of  stimulation.  Thus,  light  is  the  adequate  stimulus  of  the 
end-organ  of  the  optic  nerve,  heat  that  of  the  end-organs  of  the 
nerves  by  which  we  perceive  the  sensation  of  warmth,  mechanical 
pressure  that  of  the  nerves  by  which  we  perceive  the  sensation  of 
pressure.  Other  kinds  of  stimuU  are  either  entirely  inactive  or  much 
less  effective  in  evoking  the  particular  sensory  response.  There  is 
every  reason  to  believe  that  the  receptor  in  the  reflex  arc  occupies  the 
same  position  in  regard  to  adequate  stimuli  as  it  does  when  it  func- 
tions as  a  sense-organ. 

Sherrington  has  shown  that  the  different  kinds  of  nerve-endings 
in  one  and  the  same  area  of  the  skin  (in  the  dog)  must  be  assumed  to 
possess  totally  different  spinal  connections,  since  the  movements 
elicited  by  stimuli  suitable  for  one  form  of  nerve-ending  are  quite 
different  from  those  elicited  by  stimuli  suitable  for  another. 

The  '  extensor-thrust  '  is  a  reflex  obtained  in  the  hind-leg  of  the 
dog,  and  characterized  by  a  brief,  strong  extension  at  the  hip,  knee, 
and  ankle.  It  is  only  elicited  by  a  certain  kind  of  mechanical  stimu- 
lation, best  in  the  spinal  dog — i.e.,  in  a  dog  whose  brain  has  been 
destroj^ed  or  severed  from  the  cord  some  time  before — by  pushing  the 
tip  of  the  finger  between  the  plantar  cushion  and  the  pads  of  the  toes. 
The  stimulus  is  similar  to  that  which  normally  liberates  the  reaction 
— namely,  the  pressure  of  the  ground  on  the  sole  of  the  foot  during 
locomotion.  The  reflex  cannot  be  obtained  by  electrical  stimula- 
tion or  by  any  kind  of  direct  stimulation  of  afferent  nerve-trunks. 
The  same  is  true  of  the  pinna-reflex  in  the  cat — i.e.,  the  backward 
crumpling  of  the  ear  elicited  by  squeezing  or  tickling  its  tip.  The 
scratch-re  Ilex,*  a  scratching  movement  of  the  hind-foot,  is  much 
more  easily  elicited  in  the  spinal  dog  by  mechanical  stimulation 
(rubbing,  tickling,  or  tapping)  applied  to  the  skin  of  the  back  behind 
the  shoulder  than  by  electrical  stimulation,  which  often  fails  to 
evoke  it  at  all.  The  puzzling  fact  that,  according  to  surgical  ex- 
perience, many  of  the  internal  organs — -e.g.,  the  ureters  and  bile- 
ducts — can  be  handled,  cut,  and  sutured  without  pain,  while  the 
passage  of  a  renal  calculus  or  a  gall-stone  may  cause  excruciating 
agony,  becomes  explicable  in  view  of  the  apparently  slight  difference 
which  sometimes  distinguishes  an  adequate  from  an  inadequate 
stimulus.  Thus  Sherrington  has  shown  that  very  distinct  reflex 
effects — e.g.,  a  rise  of  blood-pressure — can  be  obtained  by  sudden 
distension  of  the  bile-duct  by  the  injection  of  salt  solution  into  its 
lumen.  Distension  is  here  the  adequate  form  of  mechanical  stimu- 
lation, and  it  is  the  form  induced  by  the  passage  of  a  calculus,  while 
nerve-cutting, although  a  mechanical  stimulus, is  not  an  adequate  one. 

*  The  scratch-reflex  is  very  easily  obtained  in  cats  during  resuscitation 
after  a  period  of  cerebral  anaemia. 


874  ^^^  CENTRAL  NERVOUS  SYSTEM 

Characteristic  Properties  of  the  Reflex  Arc. — Conduction  in  reflex 
arcs  shows  certain  peculiarities  when  compared  with  the  conduction 
in  nerve-trunks  already  studied  (p.  755) :  (i)  The  direction  of  the 
reflex  conduction  cannot  be  reversed.  There  is  an  absolute  block 
on  the  passage  of  impulses  backwards  through  a  synapse.  (2)  The 
velocity  of  conduction  over  the  whole  reflex  arc  is  much  smaller 
than  over  a  nerve-trunk  of  equal  length.  Both  of  these  differences 
depend  mainly  on  the  fact  that  the  impulses  must  be  transmitted 
from  one  neuron  to  another,  and  very  likely  on  a  fundamental 
property  of  the  synapse.  The  delay  or  '  lost  time  '  in  the  discharge 
of  the  efferent  impulses  which  constitute  the  reflex  response  to  the 
excitation  of  an  afferent  path  increases  with  the  complexity  of  the 
response — that  is,  with  the  number  of  neurons  and  therefore  of 
synapses  involved  in  it.  (3)  The  reflex  arc  is  easily  fatigued,  easily 
affected  by  deprivation  of  oxygen  and  by  drugs,  in  comparison  with 
the  nerve-trunk.  This  difference  is  due  to  the  portion  of  the  arc 
in  the  grey  matter,  including  the  synapse  or  synapses.  Fatigue 
expresses  itself  by  an  increase  in  the  degree  of  block  or  resistance  to 
the  passage  of  impulses  along  the  arc.  (4)  The  reflex  end-effect  may 
much  outlast  the  stimulus — in  other  words,  a  marked  '  after-dis- 
charge '  is  characteristic  of  reflexes.  The  more  intense  the  stimulus 
which  liberates  the  end-effect,  the  greater  is  the  duration  of  the  after- 
discharge.  For  example,  the  '  crossed  extension  reflex  '  (extension 
at  the  knee,  ankle,  and  hip,  produced  in  the  spinal  dog  by  stimula- 
tion of  the  skin  of  the  opposite  or  contralateral  hind-limb),  when 
provoked  by  a  stimulus  of  more  than  a  certain  intensity,  may  outlast 
the  stimulation  by  ten  or  fifteen  seconds,  and  the  after-discharge 
may  be  stronger  than  any  other  part  of  the  reflex  (Sherrington). 
(5)  A  succession  of  impulses  may  easily  pass  along  a  reflex  arc  when 
one  of  the  series  would  fail  to  pass  (temporal  summation).  This 
does  not  occur  in  a  nerve-trunk.  The  first  stimulus,  though  itself 
unable  to  produce  the  reflex  effect,  facihtates  the  action  of  succeeding 
stimuli,  so  that  summation  of  the  impulses  occurs  in  the  cord 
(Stirling).  A  stimulus — e.g.,  a  make-induction  shock,  far  too  weak 
to  produce  the  scratch-reflex  when  applied  once  only  to  a  point  of 
that  area  of  skin  from  which  the  reflex  is  normally  elicited — has  been 
seen  to  cause  the  reflex  after  more  than  forty  shocks  had  been 
delivered  at  the  rate  of  eighteen  per  second.  The  facilitation  of  the 
passage  of  an  impulse  by  the  previous  passage  of  impulses  along  the 
same  reflex  path  recalls  a  somewhat  similar  phenomenon  already 
alluded  to  in  connection  with  the  conduction  of  the  propagated 
disturbance  in  nerve-fibres  (p.  765),  although  in  the  case  of  the  reflex 
arc  the  effect,  it  may  be  supposed,  is  exerted  upon  the  fields  of 
conjunction,  including  the  synapses,  between  the  different  neurons. 
There  is  reason  to  believe  that  summation  in  the  reflex  arc  is  mainly 
achieved  by  the  removal  of  block  or  resistance.    The  phenomenon  of 


FUNCTIONS  OF  THE  SPINAL  CORD  875 

facilitation  is  probably  of  great  importance  in  the  acquirement  of 
new  reactions  and  in  rendering  these  acquisitions  stable.  It  is  prob- 
ably one  of  the  main  physiological  foundations  of  habit,  and  there- 
fore of  education.  In  tliis  connection  it  is  important  to  note  that 
the  very  same  repetition  of  stimuli  wliicli  leads  to  facilitation  leads 
to  fatigue  when  the  stinmli  are  applied  in  too  rapid  succession. 
(6)  The  rhythm  and  intensity  of  the  reflex  end-effect  correspond 
much  less  closely  with  the  rhythm  and  intensity  of  the  stimulus  than 
in  nerve-trunks.  (7)  The  phenomena  of  refractory  period  (p.  155), 
inhibition  and  '  sliock,'  are  much  more  conspicuous  in  the  reflex  arc 
than  in  nerve-trunks. 

Inhibition  in  Reflex  Action. — Specio.l  emphasis  must  be  laid  upon 
the  part  played  by  inhibition  in  reflex  actions.  For  the  proper 
carrying  out  of  many  reflex  movements  it  is  necessary  not  only  that 
the  appropriate  effector  organ,  the  appropriate  muscle,  or  group  of 
muscles,  should  be  caused  to  contract  at  the  proper  time,  but  that 
their  contraction,  or  that  of  other  muscles,  should  be  diminished  or 
abolished  by  inhibition,  or  even  rendered  for  a  certain  period  im- 
practicable by  the  establishment  somewhere  in  the  reflex  arc  of  a 
refractory  state,  which  is  itself  a  phenomenon  of  inhibition.  There  is 
good  evidence  that  this  is  a  central  inhibition — i.e.,  it  depends  on 
some  process  occurring  in  the  spinal  portion  of  the  reflex  arc. 

As  an  example  of  the  numerous  class  of  reflexes  in  which  the 
excitation  of  certain  muscles  is  accompanied  by  the  inhibition  of 
their  antagonists  (reciprocal  inhibition),  we  may  take  the  '  flexion 
reflex,'  the  flexion  at  the  knee,  hip,  and  ankle  of  the  hind-limb 
readily  elicited  in  the  spinal  dog  by  '  nocuous  '  or  harmfui  stimuli 
(such  as  a  prick,  a  strong  squeeze,  chemical  agents,  or  excessive 
heat),  or  by  electrical  stimuli  applied  to  the  skin  of  the  limb  or  of 
any  afferent  nerve  of  the  limb. 

Sherrington  has  shown  that  when  the  legs  of  the  animal  are  so 
prepared  that  only  the  flexors  can  act  on  one  knee,  and  only  the 
extensors  on  the  other,  stimulation  of  symmetrical  points  on  the 
two  sides  in  the  area  of  skin  (receptive  field)  from  which  the  flexion 
reflex  can  be  evoked  causes  contraction  (excitation)  of  the  flexors  and 
simultaneous  relaxation(inl)ibition)of  the  tone  of  the  extensors.  The 
same  is  true  when  corresponding  afferent  nerve-twigs  are  stimulated 
on  the  two  sides.  From  this  it  is  inferred  that  each  of  the  nerve-fibres 
from  the  receptive  field  of  the  reflex  divides  in  the  cord  into  two  sets 
of  end-branches  {e.g.,  collaterals) — a  set  which  produces  excitation 
when  it  is  stimulated,  and  another  set  which  produces  inhibition. 

Reversal  of  Reflexes. — The  difference  in  action  is  specific  in  the 
sense  that  no  mere  change  in  the  kind  or  intensity  of  stimulation 
affects  it.  Yet  there  are  facts  which  show  that  the  specificity  is  not 
absolutely  immutable,  and  that  a  change  of  conditions  in  the  spinal 
cord  may  permit  excitation  of  a  given  group  of  muscles  to  be  pro- 


876  THE  CENTRAL  NERVOUS  SYSTEM 

duced  by  the  stimulation  of  an  afferent  path  which  is  primarily 
inhibitory  for  them.  One  of  the  most  striking  illustrations  of  this 
possibility  is  seen  in  the  action  of  strychnine.  Stimulation  of  the 
internal  saphenous  nerve  below  the  knee — say  in  a  dog  after  removal 
of  the  cerebrum — is  known  always  to  produce  inhibition  of  the 
portion  of  the  quadriceps  extensor  whose  contraction  causes  the 
knee-jerk. 

If  now  the  animal  be  poisoned  by  a  small  dose  of  strychnine, 
stimulation  of  the  nerve  causes  no  longer  reflex  relaxation,  but  reflex 
contraction  of  the  muscle.  This  fact  indicates  that  the  essential 
action  of  strychnine  is  something  different  from  a  mere  reduction  of 
the  resistance  to  the  spread  of  impulses  in  the  cord  (Sherrington). 
Tetanus  toxin  produces  a  similar  effect,  though  more  slowly. 

The  reversal  of  the  depressor  reflex  on  the  blood-pressure  has  been 
previously  alluded  to  (p.  185).  A  different  type  of  reversal,  and  one 
of  most  interest  in  connection  with  the  co-ordination  of  reflexes,  is 
illustrated  by  such  observations  as  the  following:  The  extensor 
thrust  is  only  obtained  by  the  adequate  form  of  stimulation  de- 
scribed on  p.  873,  when  the  hind-limb  is  in  a  condition  of  flexion. 
When  the  leg  is  passively  extended  at  the  time  when  the  stimulus  is 
applied,  the  response  is  not  the  extensor  thrust,  but  flexion  of  the 
leg  and  thigh  (direct  flexion  reflex).  The  passive  assumption  of  a 
condition  of  flexion  at  the  knee  and  thigh  appears,  accordingly,  to 
favour  the  extensor  reaction  (Sherrington).  The  observations  of 
Magnus  have  shown  that  such  relations  are  general;  for  example, 
the  reaction  is  usually  extension  when  the  opposite  posterior  limb 
is  flexed  at  the  time  of  stimulation,  and  flexion  when  the  opposite 
leg  is  extended.  In  the  spinal  cat,  stimulation  applied  to  the  tail, 
especially  near  the  root,  elicits  always  a  stroke  towards  the  side  on 
which  at  the  time  of  stimulation  the  muscles  are  extended.  The 
phenomenon  is  dependent  upon  the  integrity  of  the  afferent  nerves 
of  the  passively  extended  or  flexed  muscles  whose  position  influences 
the  reflex,  and  of  the  afferent  nerves  of  the  tendons  and  fascia  re- 
lated to  them.  The  condition  of  the  reflex  centres  is  in  some  way 
influenced  by  impulses  conducted  along  those  afferent  paths. 

Not  only  is  the  tone  of  the  extensors  diminished  or  abolished 
during  the  activity  of  the  flexors,  but  the  contraction  of  the  knee 
extensors  evolved  by  striking  the  patellar  tendon,  which  is  called 
the  knee-jerk,  either  fails  to  appear,  or  appears  but  feebly,  when  the 
flexion  reflex  is  simultaneously  elicited,  even  when  the  mechanical 
antagonism  of  the  flexor  contraction  has  been  eliminated  by  pre- 
viously detaching  the  flexors  from  the  knee. 

The  Knee-jerk. — This  is  sometimes  termed  a  pseudo-reflex.  For 
certain  authorities  believe  that  the  mechanism  by  which  it  is  pro- 
duced is  different  from  that  concerned  in  the  reflex  blinking  of  the 
eyelid,  or  the  reflex  retraction  of  the  testicle,  or  the  drawing-up  of 


FUNCTIONS  OF  THE  SPINAL  CORD  877 

the  foot  when  the  sole  is  tickled.  The  knee-jerk  is  obtained  in 
undiminished  strength  when  the  nerves  of  the  ligamentum  patella 
have  been  divided.  It  is  therefore  not  a  reflex  movement  caused  by 
stimulation  of  afferent  nerves  coming  from  the  tendon, and  the  name 
'  tendon-reflex  '  is  clearly  a  misnomer.  But  that  it  is  related  in  some 
way  or  other  to  afferent  impulses  is  certain,  for  division  of  the 
posterior  roots  that  enter  into  the  anterior  crural  nerve  abolishes 
the  knee-jerk.  The  phenomenon,  according  to  these  authors  who 
deny  that  it  is  a  true  reflex,  comes  under  the  head  of  what  is  called 
myotatic  irritability — that  is,  it  depends  on  mechanical  stimulation 
of  the  shghtly-stretched  muscle  by  the  pull  of  the  tendon  when  it  is 
struck.  It  is  necessary  for  this  stimulation  that  the  muscle  should 
be  to  a  certain  extent  tonicaUy  contracted.  So  that  when  the 
afferent  fibres  are  interrupted,  or  the  grey  matter  of  the  cord  dis- 
organized, and  the  reflex  tone  abolished,  the  knee-jerk  disappears. 
The  strongest  objection  to  considering  it  an  ordinary  reflex  is  the 
shortness  of  the  interval  which  elapses  between  the  tap  and  the  jerk, 
which,  according  to  some  observers,  is  not  much  greater  than  the 
latent  period  of  the  quadriceps  muscle  for  direct  electrical  stimula- 
tion, as  measured  under  the  ordinary  conditions  of  its  contraction. 
There  is  no  doubt  that  the  interval  is  very  brief,  although  somewhat 
conflicting  results  have  been  obtained  by  different  observers  for  the 
corrected  latency — that  is,  the  period  between  stimulus  and  response 
minus  the  latent  period  of  the  muscle.  In  man  this  period  seems 
to  be  about  002  second.  In  a  dog  with  divided  spinal  cord  the 
interval  was  found  to  be  0014  to  002  second  (Applegarth) ;  in  the 
rabbit  only  0008  to  0005  second  (Waller  and  Gotch).  Recent 
observations  in  which  the  electrical  response  of  the  muscle  as  re- 
corded by  the  string  galvanometer  was  employed  instead  of  the 
contraction  have  yielded  results  not  very  different  from  those 
obtained  by  the  older  methods,  ooii  to  0-015  second  according  to 
Synder.  Taking  account  of  the  newer  observations  on  the  velocity 
of  the  nervous  impulse  (p.  767),  it  would  appear  that  the  inter\-al  is 
not  really  too  short  to  prevent  the  knee-jerk  from  being  classified 
as  a  true  reflex  contraction,  although  a  very  brief  one.  The  rein- 
forcement of  the  knee-jerk  is  referred  to  under  another  heading 
(p.  883).  It  is  admitted  that,  in  addition  to  the  direct  stimu- 
lation of  the  muscle  on  the  same  side,  the  tendon-tap  may  cause 
also  a  true  reflex  knee-jerk  on  the  opposite  side,  the  interval  between 
tap  and  contraction  being  about  J  second. 

Spread  or  Irradiation  of  Reflex  Action. — As  the  strength  of  the 
stimulus  which  has  been  evoking  a  given  reflex  movement  is  in- 
creased, the  reflex  effect  becomes  more  and  more  extensive,  spreading 
out  or  irradiating  in  various  directions.  If,  for  example,  the  reflex 
in  question  is  the  flexion  reflex  elicited  by  stimulation  of  the  plantar 
surface  of  the  hind-foot  in  the  spinal  animal,  increase  of  the  stimulus 


878  THE  CENTRAL  NERVOUS  SYSTEM 

will  cause,  in  addition  to  flexion  of  the  same  hind-foot,  extension  of 
the  opposite  hind-limb,  then  in  the  homonymous  fore-limb  {i.e.,  the 
limb  on  the  same  side)  extension  at  the  elbow  and  retraction  at  the 
shoulder,  then  certain  definite  movements,  the  details  of  which  need 
not  detain  us  here,  in  the  opposite  fore-limb,  and  ultimately  also 
definite  movements  of  the  head  and  tail  (Sherrington).  Obviously 
there  is  a  certain  orderliness  in  the  spread  of  the  reflexes;  they 
follow  a  certain  regular  march;  the  irradiation  in  the  tangle  of  the 
spinal  paths  is  not  an  indiscriminate  one.  The  same  fact  emerges 
quite  as  clearly  when  other  reflexes  are  studied  in  a  similar  way ;  and 
certain  laws  or  rules  which  define  the  spread  of  the  impulses  in  spinal 
reflexes  have  been  deduced.  For  descriptive  purposes,  in  dealing 
with  reflex  action,  it  is  convenient  to  consider  each  lateral  half  of 
the  cord  as  divisible  into  regions  each  related  on  the  one  hand  to  a 
certain  area  of  the  receptive  surface  (skin),  and  on  the  other  to 
certain  muscles.  Such  regions  are  those  of  the  neck,  including  the 
pinna  (cervical),  the  fore-limb  (brachial),  the  trunk  (thoracic),  the 
hind-limb  (crural),  and  the  tail  (caudal).  According  to  their  rela- 
tion to  these  regions  the  spinal  reflexes  can  be  classified  as  '  short  ' 
or  '  long.'  The  short  spinal  reflexes  are  those  in  which  the  muscular 
response  takes  place  in  the  same  region  as  the  application  of  the 
stimulus.  The  long  reflexes  are  those  evoked  when  the  stimulus  is 
applied  to  the  receptive  field  of  one  region,  and  the  response  occurs 
in  the  musculature  of  another  region.  For  the  short  reflexes 
Sherrington  has  given  a  number  of  rules,  which  may  be  .stated  as 
follows:  (i)  The  closer  together  their  spinal  segments,  thd  easier  is 
it  for  stimulation  of  a  given  efferent  root  to  excite  reflex  contractions 
of  muscles  supplied  by  a  given  afferent  root.  (2)  For  each  afferent 
root  there  exists  in  its  own  spinal  segment  (of  course,  on  its  own  side 
of  the  cord)  a  reflex  motor  path  of  as  low  a  threshold  {i.e.,  as  easily 
set  into  action)  and  of  as  high  potency  {i.e.,  producing  as  great  a 
reflex  effect)  as  any  open  to  it  anywhere.  It  has  been  shown  that 
the  afferent  nerves  of  a  skeletal  muscle  are  derived  from  the  spinal 
ganglion  corresponding  to  the  segment  of  the  cord  containing  its 
motor  cells.  (3)  Motor  mechanisms  for  the  skeletal  musculature 
lying  in  the  same  region  of  the  cord,  and  in  the  selfsame  spinal 
segment,  show  markedly  unequal  accessibility  to  the  local  afferent 
channels  as  judged  by  the  reflex  contractions  produced.  For 
example,  the  reflex  contraction  of  the  flexors  of  the  knee  on  the 
stimulated  side,  and  of  the  extensors  of  the  opposite  knee,  is  in 
many  animals  much  more  easily  elicited  than  contraction  of  the 
extensors  of  the  homonymous  and  the  flexors  of  the  contralateral 
{i.e.,  opposite)  side.  This,  however,  is  not  because  the  last-named 
extensors  and  flexors  are  really  incapable  of  being  reflexly  affected 
through  the  afferent  fibres  of  the  corresponding  spinal  segments,  but 
because  the  reflex  effect  produced  by  them  is  in  this  case  not  con- 


FUNCTIONS  OF  THE  SPINAL  CORD  879 

traction,  but  inhibition.  (4)  The  groups  of  motor  cells  contempor- 
aneously discharged  by  spinal  reflex  action  innervate  synergic 
muscles  (muscles  which  act  in  the  same  direction  in  effecting  a 
harmonious  movement),  and  not  antergic  muscles  (which  antagonize 
each  other). 

This  disproves  the  old  idea  that  the  movements,  caused  by  ex- 
citation of  an  efferent  spinal  root,  are  co-ordinated  synergic  move- 
ments, since  at  many  joints  the  flexors  and  extensors  both  receive 
motor  fibres  from  one  and  the  same  root,  and  stimulation  of  the 
root  must  simultaneously  excite  antagonistic  muscles.  '  The 
collection  of  fibres  in  a  motor  spinal  root  does  not  represent  a  reflex 
figure — i.e.,  a  number  of  simple  reflexes  occurring  simultaneously — 
nor  does  the  receptive  field  of  a  reflex  correspond  with  the  distribu- 
tion of  an  afferent  root.' 

(5)  It  follows  from  (i),  (2),  and  (4)  that  the  spinal  reflex  move- 
ment which  can  be  elicited  in  and  from  any  one  spinal  region  will 
exhibit  much  uniformity  even  when  the  exciting  stimulus  is  applied 
at  different  and  distant  points  within  the  receptive  field.  The 
flexion  reflex  of  the  hind-limb,  e.g.,  will  have  the  same  general  char- 
acter— i.e.,  flexion  of  each  of  the  three  main  joints — whatever  part 
of  the  surface  of  the  limb  is  stimulated.  Yet  the  flexion  movement 
will  be  strongest  at  the  joint  whose  flexors  are  innervated  by  motor 
cells  situated  in  a  spinal  segment  near  the  entrance  of  the  afferent 
fibres  from  the  stimulated  skin  area. 

For  the  long  spinal  reflexes  it  is  less  easy  to  deduce  definite  rules, 
for  they  can  be  less  easily  and  constantly  evoked  than  the  short 
reflexes.  The  so-called  laws  of  spread  formulated  by  Pfltiger  for 
the  long  spinal  reflexes,  and  based  mainly  on  observations  made 
in  the  brainless  frog  and  on  clinical  records  in  cases  of  spinal  lesion 
in  man,  need  not  be  stated  here.  For  Sherrington  has  shown  that 
they  require  serious  modification.  Especially  is  this  true  of  Pfliiger's 
fourth  law,  that  the  reflex  irradiation  spreads  always  more  easily 
up  in  the  direction  of  the  medulla  oblongata,  so  that  stimulation  of 
a  fore-limb  does  not  cause  reflex  contraction  of  a  hind-limb,  although 
excitation  of  a  hind-limb  may  cause  movement  of  one  or  both  fore- 
limbs.  This  law  does  not  hold  in  the  mammal.  As  a  rule,  indeed, 
irradiation  takes  place  more  easily  down  than  up  the  cord.  Excita- 
tion of  the  skin  of  the  pinna  easily  causes  reflex  movements  of  the 
limbs,  while  the  reverse  is  rare.  Reflex  movements  of  the  hind- 
limb  in  the  spinal  animal  are  more  easily  evoked  by  stimulation  of 
the  fore-limb  than  movements  of  the  fore-limb  by  stimulation  of 
the  hind.  It  is  easier  for  the  irradiation  to  cross  the  cord  from 
hind-limb  to  hind-hmb  than  to  pass  up  from  hind-  to  fore-limb; 
but  it  is  often  easier  for  irradiation  to  occur  down  the  cord  from 
fore-  to  hind-limb  than  across  the  cord  from  one  fore-limb  to  the 
other.     Afferent  channels  from  the  skin  of  the  shoulder,  tlirough 


88o  THE  CENTRAL  NERVOUS  SYSTEM 

which  the  gcratch-reflex  is  discharged  (in  the  dog),  are  freely  con- 
nected with  efferent  paths  to  the  muscles  of  the  hip,  knee,  and  ankle 
by  an  uncrossed  path  descending  the  lateral  column  (Sherrington). 
In  cats,  after  temporary  occlusion  of  the  cerebral  circulation,  which 
throws  the  brain  out  of  gear,  it  is  easy  to  elicit  movements  of  the 
hind-legs  by  pinching  the  fore-paws  or  the  skin  of  the  upper  part 
of  the  bod3^  The  scratch-reflex  can  also  be  very  readily  evoked, 
and  in  great  intensity,  by  stimulating  the  pinna,  and  is  not  confined 
to  the  side  stimulated.  In  anaemia  of  the  brain  and  (cervical)  cord 
and  subsequent  resuscitation,  homolateral  reflexes  {i.e.,  on  the 
same  side  as  the  stimulus)  are  submerged  later  and  emerge  sooner 
than  contralateral  reflexes  whose  centres  lie  in  the  area  which  was 
rendered  anaemic  (Pike,  Guthrie,  and  Stewart). 

Co-Ordination  of  Reflexes. — The  co-ordination  or  orderly  combina- 
tion of  muscular  actions  for  the  production  of  appropriate  and  har- 
monious movements  is  one  of  the  most  important  functions  of  the 
central  nervous  system.  Both  the  brain  and  the  cord  take  a  share 
in  this  co-ordination.  The  role  of  the  brain  will  be  considered  later 
on,  but  it  is  essential  to  recognize  now  that  many  of  the  movements 
which  the  brain  directs  represent  spinal  reflexes  already  synthesized, 
compounded,  or  co-ordinated  in  a  very  high  degree.  This  is  the 
reason  why,  in  the  spinal  animal,  the  inexperienced  observer  may 
sometimes  be  startled  by  the  apparently  '  purposive  character  '  of 
a  reflex  movement — the  scratch-reflex  in  the  dog  or  cat,  e.g.,  or  the 
extensive  reflex  movements  of  the  hind-legs  of  a  brainless  frog 
when  the  skin  is  pinched  or  painted  with  dilute  acid,  so  plainly 
directed  to  the  seat  of  irritation.  When  a  drop  of  acid  is  applied 
to  the  flank  of  such  a  frog,  it  will  attempt  to  wipe  it  off  with  the 
foot  which  is  situated  most  conveniently.  If  this  foot  be  held,  it 
will  use  the  other.  These  reactions  are  necessarily  purposive  in 
character,  since  they  have  been  evolved  with  reference  to  the  ad- 
vantage of  the  organism  as  a  whole.  They  are  the  sort  of  complex 
reactions  which  the  intact  animal  would  have  had  to  improvise 
by  the  combination  of  a  considerable  number  of  simple  movements 
when  it  was  executing  such  defensive  reactions,  with  the  conscious 
purpose  of  escaping  from  the  irritant,  were  they  not  already  present 
as  purposive  reflexes  in  the  ready-made  condition. 

In  the  combining  of  reflexes  we  may  distinguish  between  simul- 
taneous combination — i.e.,  the  combination  of  reflex  actions  taking 
place  at  the  same  time — and  successive  combination — i.e.,  the 
combination  of  reflexes  in  such  a  way  that  they  follow  each  other 
in  an  orderly  sequence.  The  facts  already  mentioned  in  speaking 
of  irradiation  afford  a  partial  explanation  of  the  co-ordination  of 
reflexes  by  simultaneous  combination.  The  movements  are  orderly 
and  harmonious  because  the  spread  of  the  reflexes  is  not  indis- 
criminate, but  follows  a  definite  '  march,'  determined  partly  by  the 


FUNCTIONS  OF  THE  SPINAL  CORD  88 1 

anatomical  relations  of  afferent  and  efferent  paths,  partly  by  the 
varying  resistance  of  the  synapses  or  other  structures  whose  proper- 
ties fix  the  threshold  value  of  the  excitation  by  which  an  arc  can  be 
forced.  In  general  it  is  not  enough  that  the  channel  of  the  final 
common  paths  (p.  871)  to  the  muscles  whosu  contraction  produces 
the  reflex  movement  should  be  thus  open  to  the  afferent  arcs  that 
elicit  the  movement ;  they  must  be  closed  to  other  afferent  arcs 
which  might  disturb  the  reflex.  Not  only  so:  there  is  evidence 
that  very  frequently  the  final  common  paths  are,  so  to  say,  more 
widely  opened  to  the  afferent  arcs  in  question  by  the  '  reinforcing  ' 
or  '  facilitating  '  influence  of  allied,  though  it  may  be  distant, 
afferent  arcs,  which  are  simultaneously  excited  (p.  883).  Further, 
the  final  common  paths  to  antagonistic  muscles  must  also  be 
temporarily  closed.  The  closing  of  these  central  connections,  or 
rather  the  raising  of  their  threshold  sufficiently  to  bar  the  impulses 
from  passing  through  the  door,  is  an  inhibitory  phenomenon.  Ex- 
citation of  the  desired  movements  and  inhibition  of  antagonistic 
movements  go  hand-in-hand  in  the  simultaneous  combination  of 
reflexes.  It  is  obvious  that  if  a  movement  is  to  be  efficiently  exe- 
cuted, it  cannot  be  the  result  of  a  compromise  between  competing 
reflexes.  A  segment  of  a  limb  can  be  either  flexed  or  extended,  but 
cannot  at  the  same  time  undergo  both  flexion  and  extension.  In 
the  interests  of  an  effective  movement,  one  or  the  other  must  give 
way  utterly.  The  reflex  which  eventually  prevails  makes  a  clear 
field  for  itself  by  inhibiting  all  other  reflexes  which  do  not  co-operate 
with  it.  For  example,  if  the  receptive  area  of  skin  from  which  the 
scratch  reflex  is  elicited  be  stimulated  and  a  painful  stimulation  be 
at  the  same  time  applied  to  the  foot,  we  do  not  obtain  a  mixed 
scratch  and  flexion  reflex,  which  would  result  in  a  confused  and 
ineffective  combination  of  movements,  but  a  pure  scratch  or  flexion 
reflex,  as  a  rule  the  latter. 

The  successive  combination  of  reflexes  is  well  illustrated  by  the 
contraction  of  the  oesophagus  in  deglutition.  First  one  portion  of 
the  tube  and  then  the  next  below  are  involved  in  the  reflex  action. 
The  combination  consists  in  the  orderly  sequence.  The  manner  in 
which  this  is  secured  in  this  class  of  reflex  action  has  been  lumin- 
ously discussed  by  Sherrington,*  but  details  cannot  be  given  here. 
While  only  allied  reflexes — i.e.,  such  as  mutually  reinforce  and 
therefore  harmonize  with  each  other — can  be  simultaneously  com- 
bined, and  antagonistic  reflexes  cannot,  both  allied  and  antagonistic 
reflexes  can  be  successively  combined.  An  example  of  the  succes- 
sive combination  of  allied  reflexes  is  the  series  of  scratch  reflexes 
caused  by  a  parasite  travelling  across  the  receptive  field  of  the 
reflex.     An  example  of  the  successive  combination  of  antagonistic 

*  '  Integrative  Action  of  the  Nervous  System,'  to  which  work  the  advanceil 
student  is  referred. 

56 


882  THE  CENTRAL  NERVOUS  SYSTEM 

reflexes  is  afforded  when  either  the  scratch  reflex  or  the  flexion 
reflex  is  induced  and  caused  to  interrupt  the  other  while  it  is  pro- 
ceeding. The  transition — e.g.,  from  flexion  to  scratch  reflex — is 
made  \\athout  any  period  of  confusion.  Thus,  if  the  scratch  reflex 
has  been  induced  and  is  being  executed,  and  the  foot  is  then  pain- 
fully stimulated,  the  scratch  reflex  immediately  ceases,  and  the 
flexor  reflex  takes  its  place.  When  the  flexor  reflex  has  termin- 
ated, the  scratch  reflex  maybe  resumed.  The  same  holds  good  for 
other  antagonistic  reflexes.  In  many  cases  the  avoidance  of  con- 
fusion is  due  to  the  inhibition  of  the  first  reflex,  or  often  to  inhibition 
of  the  set  of  muscles  which  were  active  in  the  first  reflex  combined 
with  excitation  of  their  antagonists  (so-called  interference).  It  is 
obvious  that  this  is  an  adaptation  of  great  importance. 

Influence  of  the  Brain  on  the  Spinal  Reflexes. — The  spinal  reflexes 
can  be  influenced  by  impulses  descending  from  the  higher  centres. 
For  {a)  it  is  a  matter  of  common  experience  that  a  reflex  movement 
may  be  to  a  certain  extent  controlled,  or  prevented  altogether  by  an 
effort  of  the  will,  and  it  is  worthy  of  remark  that  only  movements 
which  can  be  voluntarily  produced  can  be  voluntarily  inhibited. 
(b)  Long-continued  muscular  contractions  may  be  caused  in  animals 
after  removal  of  the  cerebral  hemispheres  by  stimulation  of  afferent 
nerves — for  example,  by  scratching  the  mucous  membrane  of  the 
mouth  in  a  '  brainless  '  frog  or  Necturus.     (c)  By  stimulation  of 
certain  of  the  higher  centres  reflex  movements  which  would  other- 
wise be  elicited  may  be  suppressed  or  greatly  delayed.     If   the 
cerebral  hemispheres  are  removed  from  a  frog,  and  one  leg  of  the 
animal  dipped  into  dilute  acid,  a  certain  interval,  the  (uncorrected) 
reflex  time,  will  elapse  before  the  foot  is  drawn  up  (p.  959).     If, 
now,  a  crystal  of  common  salt  be  applied  to  the  optic  lobes,  or 
corpora  bigemina,or  the  upper  part  of  the  spinal  cord,  and  the  experi- 
ment repeated,  it  will  be   found  either  that  the  interval  is  much 
lengthened  or  that  the  reflex  disappears  altogether.     Stimulation 
of  the  optic  lobes  relaxes  the  reflex  sexual  embrace  of  the  male  frog 
when  it  is  present.     From  such  experiments  it  has  been  concluded 
that  centres  which  can  inhibit  the  spinal  reflexes  are  situated  in  the 
thalamus,  the  corpora  bigemina  and  the  medulla  oblongata  of  the 
frog.     In   mammals,   also,   there  is  evidence  of  the  existence   of 
mechanisms  in  the  brain,  the  excitation  of  which  diminishes  the 
reflex  excitability  of  the  cord.     For  example,  stimulation  of  the 
frontal  convolutions  in  the  dog  causes  a  diminution  in  the  height 
of  reflex   contractions   of  the   limbs.      Strong   stimulation   of  an 
afferent  nerve    may  abolish  or  delay  a  reflex  movement  which  is 
being    elicited    through    other   receptors,     {d)  If    such    inhibitory 
mechanisms  exist,  it  is  to  be  supposed  that  elimination  of  the  brain 
will  render  it  easier  to  elicit  reflexes  from  the  cord.     Experiment 
shows  that  this  is  actually  the  case.     An  animal  like  a  frog  responds 


FUNCTIONS  OF  THE  SPINAL  CORD  883 

to  stimuli  by  reflex  movements  more  readily  after  the  medulla 
oblongata  lias  been  divided  from  the  spinal  cord  or  the  brain  re- 
moved. In  the  dog  the  scratch  reflex  is  elicited  more  easily  after 
removal  of  the  cerebral  cortex  or  its  elimination  by  cerebral 
anaemia.  In  the  guinea-pig,  after  extirpation  of  the  cortex  of  one 
hemisphere,  the  scratch  reflex  is  more  readily  evoked  on  the  side 
of  the  lesion  (Brown). 

That  the  brain  exerts  more  than  a  merely  inhibitory  influence  on 
the  production  of  reflex  movements  is  suggested  by  many  facts. 
The  knee-jerk,  for  example,  is  increased  or  '  reinforced  '  if  an  instant 
before  the  tendon  is  struck  the  patient  makes  a  voluntary  movement 
or  is  acted  on  by  a  sensory  stimulus  (Bowditch  and  Warren).     In 
health  it  varies  in  strength  with  many  circumstances  which  affect 
the  activity  of  the  central  nervous  system  as  a  whole  (Lombard, 
etc.).     It  often  disppears  in  pathological  lesions,  situated  high  up 
in  the  cord  in  man,  and  is  markedly  impaired  after  high  section  of 
the  cord  in  dogs.     In  hemiplegia  (paralysis  of  one  side  of  the  body, 
caused  by  disease  in  the  brain)  the  cutaneous  reflexes  on  the  para- 
lyzed side  may  sometimes  be  absent  for  years.     Some  observers 
have  even  gone  so  far  as  to  say  that  under  normal  conditions  the 
so-called  spinal  reflexes  are  really  cerebral — in  other  words,  that 
the  afferent  impulses  run  up  to  the  brain  and  there  discharge  efferent 
impulses,  which  pass  down  to  the  motor  cells  of  the  anterior  horn 
and  cause  their  discharge.     It  may  be  admitted  that  there  is  no 
physiological  ground  for  supposing  that  the  afferent  impulses  which 
have  to  do  with  the  reflex  contraction  of  the  muscles  of  the  leg 
when  the  sole  is  tickled,  stop  short  at  the  motor  cells  of  those  spinal 
segments  from  which  the  efferent  nerves  come  off,  while  the  af- 
ferent impulses  which  have  to  do  with  the  sensation  of  tickling  pass 
up  to  the  brain.     The  probability  is  that  under  ordinary  circum- 
stances such  afferent  impulses  pass  up  the  cord  in  long  afferent 
paths,  as  well  as  directly  towards  the  motor  cells  along  those  fibres 
of  the  posterior  roots  and  their  collaterals  which  bend  fonv^ard  into 
the  anterior  horn  at  the  level  of  their  entrance  into  the  cord.     And 
the  only  question  is  whether,  as  a  matter  of  fact,  the  spinal  motor 
cells  are  most  easily  discharged  by  the  impulses  that  reach  them 
directly,  or  by  the  impulses  that  come  down  to  them  by  the  round- 
about way  of  the  brain,  and  the  efferent  fibres  that  connect  it  \snth 
the  cord.     It  is  evident  that  the  answer  to  this  question  need  not 
be  the  same  for  all  kinds  of  animals.     It  may  well  be  that  in  the 
higher  animals,  in  which  the  cortex  has  undergone  a  relatively  great 
development,  the  spinal  motor  mechanisms  are  more  easily  dis- 
charged from  above  than  from  below,  while  in   lower  animals  the 
opposite  may  be  the  case.    Wht^i  the  cord  is  cut  off  from  the  braini 
the  afferent  impulses  may  overflow  more  easily  into  the  spinal  motor 
cells  since  their  alternative  path  is  blocked.     In  the  frog,  where 


884  ^^^  CENTRAL  NERVOUS  SYSTEM 

there  is  already  a  beaten  track  between  the  posterior  root-fibres 
and  the  cells  of  the  anterior  horn,  this  overflow  may  be  established 
immediately  after  section  of  the  cord,  and  may  of  itself  lead  to  an 
exaggeration  of  the  reflexes.  In  animals  like  the  dog  a  longer  time 
may  be  necessary  before  the  unaccustomed  route  from  the  end 
arborizations  of  the  afferent  axons  and  their  collaterals  to  the 
dendrites  or  the  bodies  of  the  motor  cells  becomes  natural  and  easy; 
in  man  a  still  longer  interval  may  be  required.  Moore  and  Oertel 
have  made  a  careful  comparative  study  of  reflex  action  after  com- 
plete section  of  the  cord  in  the  cervical  or  upper  dorsal  region,  and 
conclude  that  the  spinal  reflexes  in  the  higher  animals  are  far  more 
dependent  on  the  upper  portions  of  the  central  nervous  system  than 
in  the  frog. 

Spinal  Shock. — The  phenomena  of  spinal  shock  and  its  varj'ing 
severity  in  different  animals  may  be  accounted  for  by  the  rupture  of 
the  paths  normally  used  in  the  reflexes.  The  theory  that  the  shock  is 
due  to  an  inhibition  set  up  by  the  mechanical  injury  is  untenable.  For 
shock  affects  only  the  portion  of  the  central  nervous  system  distal  (or 
aboral)  to  the  lesion.  Wlien  a  dog  is  allowed  to  live  after  transection 
of  the  cord  in  the  lower  cervical  region  till  shock  has  been  recovered 
from,  a  second  transection  distal  to  the  first  is  followed  by  only  slight 
and  very  transient  depression  of  the  reflex  power,  although  the  direct 
effect  of  the  second  injury  ought,  of  course,  to  be  as  great  as  that  of  the 
first.  Finally,  according  to  Sherrington,  the  condition  of  the  spinal 
reflex  arcs  in  shock  dift'ers  from  the  condition  caused  by  inhibition,  and 
resembles  rather  a  general  spinal  fatigue  in  which  conduction  along  the 
arc  and  especially  across  the  synapses  is  difficult  and  uncertain.  This 
condition  is  supposed  to  be  due  to  the  loss  of  a  '  tonic  '  influence  of 
higher  centres,  assumed  to  be  necessary  for  the  maintenance  of  the 
normal  conductivity  of  the  arc.  These  cranial  centres,  if  they  exist,  or, 
at  least,  the  most  efficient  of  them,  must  be  assumed  to  be  situated 
distal  to  the  cerebral  cortex,  probably  in  the  pons  or  mid-brain.  For 
section  just  behind  the  pons  causes  much  more  severe  shock  than 
removal  of  the  cerebral  hemispheres. 

Peripheral  Reflex  Centres. — The  question  whether  any  reflex  centres 
exist  outside  of  the  spinal  cord  and  brain,  and  especially  in  the  sympa- 
thetic ganglia,  has  been  the  subject  of  a  lengthy  controversy.  That 
the  spinal  ganglia  cannot  act  as  reflex  centres  is  generally  acknowledged, 
and  it  is  not  difficult  to  see  that,  for  anatomical  reasons,  this  must  be  so. 
A  reflex  arc  must,  so  far  as  we  know,  in  all  highly -organized  animals 
include  at  least  two  neurons.  There  is  no  proof  that  an  afferent 
impulse  can  ascend  an  axon  to  a  cell-body  and  there  excite  an  efferent 
impulse,  which,  descending  the  same  axon  in  a  separate  set  of  fibrils, 
gives  rise  to  a  reflex  contraction,  or  a  reflex  secretion.  Now,  the  cells 
of  a  spinal  ganglion  represent  the  original  neuroblasts  from  which  the 
posterior  root-fibres  grew  out  as  processes  towards  the  cord  on  the  one 
side  and  the  periphery  on  the  other.  A  sensory  fibre  passing  into  the 
ganglion  makes  connection  with  a  cell  by  a  T-shaped  junction  and 
passes  on  its  course  again.  No  aitcrent  fibres  run  from  the  nerve-trunk 
into  the  ganglion,  to  end  in  arborizations  around  the  ganglion  cells, 
and  no  efferent  fibres  arise  from  ner\'c-cells  in  the  ganglion  to  pass  out 
into  the  trunk.  For  although  a  slightly  greater  number  of  meduUated 
fibres  of  small  calibre  is  found  in  a  spinal  nerve-trunk  immediately 


FUNCTIONS  OF  THE  SPINAL  CORD  885 

distal  to  the  junction  of  tlic  roots  than  in  both  roots  taken  together,  this 
appears  to  be  due  to  tlie  passage  into  the  nerve  (from  the  grey  ramus 
communicans)  of  mcduUatcd  fibres  which  end  in  the  bloodvessels  or 
other  tissue  of  the  e;ang]ion  (Dale).  Here  it  is  evident  that  there  is  no 
possibility  of  a  complete  reflex  arc.  Indeed,  it  is  not  certain  that  the 
normal  afferent  impulses  pass  through  the  bodies  of  the  spinal  ganglion 
cells  at  all.  For  (i)  a  negative  variation  can  be  observed  in  the  posterior 
roots  above  the  ganglia  on  stimulation  of  the  trunk  of  a  frog's  sciatc 
nerve  more  than  two  days  after  the  death  of  the  animal,  when  the 
ganglion  cells  may  be  supposed  to  have  completely  lost  their  vitality, 
and  when  no  reflex  negative  variation  can  be  detected  in  the  central 
stump  of  a  severed  anterior  root  on  excitation  of  the  sciatic  or  the 
corresponding  posterior  root.  Such  a  reflex  action  current  is  normally 
obtainable  from  a  fresh  preparation.  (2)  When  the  blood-supply  of  the 
posterior  root-fibres  anrl  the  ganglion  is  cut  off  without  killing  the  frog, 
the  nerve  impulse  is  still  conducted  by  the  fibres,  as  is  shown  by  the 
reflex  movements  elicited  on  stimulation  of  the  central  end  of  tne  sciatic, 
at  a  time  when  the  nerve-cells  show  marked  histological  alterations. 

(3)  Prolonged  excitation  of  the  posterior  roots  or  the  mixed  nerve  causes 
no  noticeable  microscopical  changes  in  the  ganglion  cells  (Steinach).* 

(4)  The  application  cf  nicotine  to  a  spinal  ganglion  does  not  hinder  the 
passage  of  impulses  through  the  corresponding  afferent  fibres.  If  it 
acts  on  spinal  ganglion  cells  as  it  does  on  sympathetic  ganglion  cells 
(p.  180),  this  must  be  because  the  impulses  do  not  require  to  traverse 
the  ganglion. 

Axon- Reflexes. — In  the  ordinary  sympathetic  ganglia, f  also,  it  is 
doubtful  whether  the  anatomical  foundation  for  a  reflex  arc  exists,  and 
the  most  careful  physiological  experiments  have  failed  to  connect  them 
with  any  reflex  function.  Sokownin,  indeed,  observed  that  stimulation 
of  the  central  end  of  the  hypogastric  nerve  caused  contractions  of  the 
bladder,  and  he  considered  these  movements  to  be  reflex,  the  centre 
being  the  inferior  mesenteric  ganglion.  I^nglcy  and  Anderson  have 
also  found  that  when  all  the  nervous  connections  of  the  inferior 
mesenteric  ganglion,  except  the  hypogastric  nerves,  are  cut,  stimulation 
of  the  central  end  of  one  hypogastric  causes  contraction  of  the  bladder, 
the  efferent  path  being  the  other  hypogastric.  In  addition,  they  have 
observed  an  apparent  reflex  excitation  of  the  nerves  which  supply  the 
erector  muscles  of  the  hairs  (pilo-motor  nerves)  through  other  sympa- 
thetic ganglia.  They  believe,  however,  that  in  neither  case  is  the  action 
truly  reflex,  but  that  it  is  caused  by  stimulation  of  the  central  ends  of 
motor  fibres,  which  come  off  from  the  spinal  cord,  and  in  passing  through 
the  ganglion  give  off  collateral  branches  to  some  of  its  cells.  In  the 
case  of  the  inferior  mesenteric  ganglion  the  spinal  fibres  passing  down 
in  the  left  hypogastric  would  send  branches  to  arborize  around  ganglion 
cells  which  give  origin  to  fibres  of  the  right  hypogastric,  and  vice  versa. 
When  the  central  end  of  the  left  hypogastric  is'  stimulated  the  excitation 
is  conducted  up  the  spinal  fibres,  and  so  reaches  their  branches,  and, 
through  the  ganglion  cells,  the  sympathetic  fibres  of  the  right  hvpo gastric, 
which  convey  it  to  the  muscles  of  the  bladder  (sec  sartorius  or  gracilis  ex- 
periment of  iviihnc,  p.  766).    Other  examples  of  such  axon-reflexes  exist. 

*  Hodge  obtained  changes.  In  such  experiments  it  is  necessary  that  the 
ganglion  should  not  be  directly  excited  by  electrotonic  currents  or  escape  of 
the  stimulating  current. 

f  The  ganglion  cells  of  Aucrbach's  and  Meissner's  plexus  in  the  intestine 
are  not  of  ordinary  sympathetic  type,  and,  as  has  been  previously  pointed 
out,  it  is  probable  that  they,  or  .some  of  them,  arc  true  reflex  centres  for  the 
stomach  and  intestines. 


886  THE  CENTRAL  NERVOUS  SYSTEM 

Reflex  Time. — When  a  reflex  movement  is  evoked,  a  measurable 
period  elapses  between  the  application  of  the  stimulus  and  the 
commencement  of  the  movement.  This  interval  may  be  called  the 
uncorrected  reflex  time  or  the  latent  period  of  the  reflex.  A  part  of 
the  interval  is  taken  up  in  the  transmission  of  the  afferent  impulse 
to  the  reflex  centre,  a  part  in  the  transmission  of  the  efferent  impulse 
to  the  muscles,  a  part  represents  the  latent  period  of  muscular 
contraction,  and  the  remainder  is  the  time  spent  in  the  centre,  or 
the  true  reflex  time.  Ordinarily  this  time,  though  absolutely  short, 
is  relatively  so  great  that  the  total  latent  period  of  a  reflex  is  much 
longer  than  when  a  similar  length  of  nerve-trunk  is  interposed  be- 
tween the  point  of  application  of  the  stimulus  and  the  muscle. 
When  the  conjunctiva  or  eyelid  is  stimulated  on  one  side  both  eye- 
lids blink.  This  is  a  typical  reflex  action  reduced  to  its  simplest 
expression,  and  the  true  reflex  time  is  correspondingly  short — only 
about  -Jjj  second  (50  <j-*).  An  additional  ^i^  second  (10  c)  is  con- 
sumed in  the  passage  of  the  afferent  impulse  along  the  fifth  nerve 
to  the  medulla  oblongata,  of  the  efferent  impulse  from  the  medulla 
to  the  orbicularis  palpebrarum  along  the  seventh  nerve,  and  in  the 
latent  period  of  the  muscle.  When  a  naked  nerve,  like  the  sciatic, 
is  stimulated,  the  true  reflex  time  is  reduced  to  j-i^  to  ^  second.  As 
estimated  by  Tiirck's  method  (p.  958),  the  uncorrected  reflex  time 
is  greatly  lengthened,  it  may  be  to  several,  or  even  many,  seconds. 
For  here  it  is  evident  that  the  time  taken  by  the  acid  to  soak 
through  the  skin  and  reach  the  nerve-endings  in  strength  sufficient 
to  stimulate  them  is  included.  But  even  when  the  peripheral 
factors  remain  constant,  the  central  factor  may  vary.  With  strong 
stimulation,  e.g.,  the  reflex  time  is  shorter  than  with  weak  stimula- 
tion. With  weak  stimuli  the  latent  period  of  the  flexion  reflex  in 
the  dog  is  usually  60  a-  or  120  cr.  It  may  even  be  as  long  as  200  cr- 
With  strong  stimuli  it  may  be  as  little  as  30  a.  Even  22  cr  has  been 
seen,  which  is  little  more  than  for  nerve-trunk  conduction.  Fatigue 
of  the  nerve-centres  delays  the  passage  of  impulses  through  them; 
and  strychnine,  while  it  increases  the  excitability  of  the  cord,  also 
lengthens  the  reflex  time. 

Reflexes  in  Disease. — In  order  that  a  reflex  action  may  take  place, 
the  reflex  arc — afferent  nerve,  central  mechanism,  and  efferent  nerve — 
must  be  complete;  and,  in  fact,  a  whole  series  of  simple  reflex  move- 
ments exists,  the  suppression,  diminution,  or  exaggeration  of  which 
can  be  used  in  diagnosis  as  tests  of  the  condition  of  the  reflex  arc.  It 
is  customary  to  divide  these  into  superficial  reflexes,  elicited  from 
receptive  fields  on  the  surface  of  the  body  [extero-ceptive  fields),  and  deep 
reflexes,  elicited  from  receptors  in  the  depth  of  the  organism  {proprio- 
ceptive fields),  especially  in  the  muscles  and  the  tendons  and  joints  con- 
nected with  them.  The  extero-ceptive  reflexes  are  normally  excited 
by  extraneous  stimuli  acting  on  the  surface  from  the  environment. 
The  proprio-ceptive  reflexes  are  normally  excited  by  changes  (muscular 

*  <r  =  oooi  second. 


FUNCTIONS  OF  THE  SPINAL  CORD 


S<7 


contractions)  occurring  in  the  body  itself,  which  changes  arc  in  turn 
usually  initiate<l  by  excitation  of  surface  receptors  by  the  environment. 
Examples  of  superficial  reflexes  arc  the  plantar  reflex  (the  drawing-up 
of  the  foot  when  the  sole  is  tickled),  the  cremasteric  reflex  (retraction  of 
the  testicle  when  the  skin  on  the  inside  of  tiie  thigh  just  below  Poupart's 
ligament  is  stroked,  especially  in  boys),  the  gluteal,  abdominal,  epigastric, 
and  interscapular  reflexes  (contraction  of  the  muscles  in  those  regions 
when  the  skin  covering  them  is  tickled).  The  behaviour  of  the  toes, 
especially  of  the  great  toe,  is  of  considerable  diagnostic  importance. 
Normally,  on  tickling  the  sole,  the  toes 
are  flexed  towards  the  planta;  but 
when  a  lesion  of  tiie  pyramidal  tract 
exists,  as  in  hemiplegia,  there  is  donsal 
instead  of  plantar  flexion,  most  marked 
in  the  case  of  the  great  toe,  and  the 
toe  moves  more  slowly  than  in  the 
healthy  person  (Babinski's  sign).  This 
is  an  instance  of  reversal  of  a  reflex 
owing  to  the  elimination  of  the  in- 
fluence of  the  cortex.  In  an  epileptic 
fit  there  is  said  to  be  a  temporary 
reversal  of  the  same  reflex,  indicating 
probably  that  the  cortex  is  temporarily 
eliminated  in  consequence  of  fatigue 
due  to  intense  and  prolonged  discharge. 
In  children  during  the  first  few  months 
of  life  stimulation  of  the  sole  causes 
normally  a  dorsal  flexion  of  the  big  toe, 
this  reversal  of  the  normal  reaction  of 
the  adult  persisting  until  the  pyra- 
midal path  has  attained  functional 
completion  (p.  820).  During  sleep 
the  reversed  reaction  (dorsal  flexion) 
is  still  obtained  for  a  time.  Examples 
of  deep  reflexes  are  the  knee-jerk  (a 
sudden  extension  of  the  leg  by  the 
rectus  femoris  and  vastus  medialis 
components  of  the  quadriceps  muscle 
when  the  ligamentum  patellar  is  sharply 
struck),  the  hccl-jerk  or  foot-jerk  (a 
movement  of  the  foot  caused  in  most 
healthy  persons,  though  not  in  all,  by 
tapping  the  tendo  Achillis),  and  the 
periosteal  radial  reflex  (a  movement 
of  flexion  and  slight  pronation  of  the 
forearm  and  hand  elicited  by  tapping 
the  lower  end  of  the  radius).  The 
jaw-jerk  (a  movement  of  the  lower  jaw  when,  with  the  mouth  open, 
the  chin  is  smartly  tapped)  and  ankle-clonus  (a  scries  of  spasmodic 
movements  of  the  foot,  brought  about  by  flexing  it  sharj)ly  on  the  leg) 
are  phenomena  of  the  same  class,  which  can  be  elicited  only  in 
disease.  Any  condition  which  impairs  the  conducting  power  of  the 
afferent  or  efferent  fibres  of  the  reflex  are  necessarily  diminishes  or 
abolishes  the  reflex  movement,  even  if  the  central  connections  are 
intact.  E.g.,  in  locomotor  ataxia  the  disappearance  of  tlic  knee-jerk 
is  one  of  the  most  important  diagnostic  signs.  This  disease  involves 
the   posterior  roots  and  the  fibres  that  continue  them  in  the  posterior 


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Knee-:Jerk 

Fig.  356. — Diagram  of  Reflf^.x  Centres 
in  Cord  (after  Hill). 


888  THE  CENTRAL  NERVOUS  SYSTEM 

column.  The  anterior  nerve-roots  are  perfectly  healthy.  The  grey 
matter  of  the  cord — at  least,  in  the  earlier  stages  of  the  disease 
— is  unaffected.  The  weak  link  in  the  chain  is  the  afferent  path. 
Wliere  the  presence  of  the  knee-jerk  is  doubtful,  it  is  necessary  to  search 
for  the  most  favourable  position  of  the  limb  for  eliciting  it  before  deter- 
mining that  it  is  absent.  The  patient  may  be  made  to  clasp  his  hands 
tightly  at  the  moment  of  the  tap  to  reinforce  the  jerk  (p.  883).  In 
anterior  poliomyelitis  (p.  848)  the  afferent  link  is  intact,  but  the  other 
two  are  broken,  and  the  reflexes  also  disappear.  Certain  lesions  which 
partially  cut  off  the  spinal  cord  from  the  higher  centres  without  affecting 
the  integrity  of  the  spinal  reflex  arcs  increase  the  strength  of  reflex 
movements  and  the  facility  with  which  they  are  called  forth.  In 
primary  spastic  paraplegia  (a  paralysis  of  the  legs  and  the  lower  portion 
of  the  body),  which  is  associated  with  degenerative  changes  in  the  lateral 
columns,  the  deep  reflexes  are  all  exaggerated.  But,  according  to  the 
best  authorities,  a  lesion  amounting  to  total  transection  of  the  cord  in 
man  abolishes  all  reflexes  below  the  lesion.  In  the  monkey  the  knee- 
jerk  may  be  tried  for  in  vain  for  weeks  after  section  of  the  cord  in  the 
middle  of  the  thoracic  region,  whereas  in  the  rabbit  it  can  be  obtained 
ten  to  fifteen  minutes  after  the  transection.  The  position  of  the  centre^ 
in  the  cord  for  the  various  reflex  movements  is  shown  in  Fig.  356. 

3.  The  Origination  of  Impulses  in  the  Spinal  Cord  (Automatism). — 
An  action  known  to  be  caused  or  conditioned  by  afferent  impulses 
is  called  a  reflex  action.  There  is  some  evidence  that  the  reflex 
centres  are  continually  in  a  state  of  activity,  and  are  not  simply 
roused  to  activity  by  the  arrival  of  the  afferent  impulses,  which 
discharge  the  reflex.  Their  condition,  when  not  discharging,  seems 
to  represent  a  state  of  balance  between  excitatory  and  inhibitory 
influences,  a  so-called  '  innervation  equilibrium,'  which  can  be  up- 
set in  one  direction  or  the  other,  according  to  the  intensity  of  the 
antagonistic  influences.  A  physiological  action  is  termed  auto- 
matic when  it  depends  upon  a  nervous  outflow  which  seems  to  be 
spontaneous,  in  the  sense  that  it  is  not  brought  about  by  any  evi- 
dent reflex  mechanism,  or,  in  other  words,  is  not  discharged  by 
afferent  impulses  falling  into  the  centre  where  it  arises,  although  it 
may  be  determined  by  substances  in  the  blood.  Automatic  actions 
being  thus  defined  in  a  negative  manner  by  the  defect  of  a  quahty, 
there  is  always  a  possibility  that  some  day  or  other  it  may  be  de- 
monstrated that  any  given  action  which  at  present  seems  automatic 
in  its  origin  depends  on  afferent  impulses  hitherto  unnoticed.  As 
a  matter  of  fact,  the  supposed  proofs  of  spinal  automatism  have  in 
more  than  one  case  vanished  with  the  advance  of  knowledge,  and  as 
the  domain  of  purely  automatic  action  has  been  narrowed,  that  of 
reflex  action  has  extended,  until  the  controversy  as  to  the  boun- 
daries between  the  two  seen:>s  not  unlikely  to  be  ended  by  the  ab- 
sorption of  the  automatic  in  the  reflex.  And  as  we  seem  almost 
driven  to  conclude  that  from  the  anatomical  standpoint  the  nervous 
system  is  essentially  a  vast  collection  of  looped  conducting  paths, 
each  with  an  afferent  portion,  an  efferent  portion,  and  connections 
between  them  formed  by  the  end  arborizations  of  the  axons  and 


FUNCTIONS  OF  THE  SPINAL  CORD  889 

their  collaterals,  the  dendrites  and  the  cell-bodies,  so  it  may  be 
that  no  strict  physiological  automatism  really  exists  either  in  cord 
or  brain,  that  every  form  of  physiological  activity — muscular  move- 
ment, secretion,  intellectual  labour,  consciousness  itself — would 
cease  if  all  afferent  impulses  were  cut  off  from  the  nervous  centres. 
Assuredly  no  neuron  is  entirely  isolated  from  other  neurons.  The 
more  the  nervous  system  is  investigated,  the  deeper  grows  the  con- 
viction of  its  essential  solidarity,  the  more  clearly  it  displays  itself 
as  a  single  mechanism,  the  most  distant  parts  of  which  are  intricately 
knit  together.  But  there  are  certain  groups  of  actions  so  widely 
separated  from  the  most  typical  reflex  actions  that,  provisionally 
at  least,  they  may  be  distinguished  as  automatic.  Such  are  the 
voluntary  movements,  and  certain  involuntary  movements,  like 
the  beat  of  the  heart.  And  we  may  proceed  to  inquire  whether  the 
spinal  cord  has  any  power  of  originating  movements  or  other  actions 
of  this  high  degree  of  automatism. 

Muscular  Tone. — So  long  as  a  muscle  is  connected  with  the  spinal 
segment  from  which  its  nerves  arise,  it  is  never  completely  relaxed ; 
its  fibres  are  in  a  condition  of  slight  tonic  contraction,  and  retract 
when  cut.  If  a  frog  whose  brain  has  been  destroyed  is  suspended 
so  that  the  legs  hang  down,  and  one  sciatic  nerve  is  cut,  the  corre- 
sponding limb  may  be  observed  to  elongate  a  little  as  compared 
with  the  other.  At  one  time  this  tone  of  the  muscles  was  supposed 
to  be  due  to  the  continual  automatic  discharge  of  feeble  impulses 
from  the  grey  matter  of  the  cord  along  the  motor  nerves.  But  it 
has  been  proved  that  if  the  posterior  roots  be  cut,  or  the  skin  re- 
moved from  the  leg,  its  tone  is  completely  lost,  although  the  anterior 
roots  are  intact.  So  that  the  tone  of  the  skeletal  muscles  depends 
on  the  passage  of  afferent  impulses  to  the  cord,  and  must  be  removed 
from  the  group  of  automatic  actions  and  included  in  the  reflexes. 

It  is  probable  that  the  tone  of  such  visceral  muscles  as  the 
sphincters  of  the  anus  and  bladder  has  also  a  reflex  element,  and 
possible  that  the  same  is  true  of  the  tone  of  the  smooth  muscular 
fibres  of  the  bloodvessels  on  which  the  maintenance  of  the  mean 
blood-pressure  so  largely  depends  (p.  183). 

Trophic  Tone. — ^The  degenerative  changes  that  occur  in  muscles, 
nerves,  and  other  tissues  when  their  connection  with  the  central 
nervous  system  is  interrupted  have  been  already  referred  to  (p.  777). 
It  is  possible  to  explain  these  changes  in  some  cases  without  the 
assumption  that  tonic  impulses  arc  constantly  passing  out  from  the 
brain  and  cord  to  control  the  nutrition  of  the  peripheral  organs; 
and  we  have  seen  that  there  is  no  real  evidence  of  the  existence  of 
specific  trophic  fibres.  But  the  degeneration  of  muscles  after  sec- 
tion of  their  motor  nerves  is  difficult  to  understand  except  on  the 
hypothesis  that  impulses  from  the  cells  of  the  anterior  horn  influence 
their  nutrition.      The  only  question  is  whether  these  are  the  im- 


Sgo-  THE  CENTRAL  NERVOUS  SYSTEM 

pulsee  to  which  muscular  tone  is  due,  and  therefore  reflex,  or  dif- 
ferent in  nature  and  automatically  diecharged.  Now,  degeneration 
of  a  muscle  is  not  usually  caused,  or  at  least  not  for  a  long  time,  by 
interruption  of  its  afferent  nerve-fibres,  as  in  locomotor  ataxia,  or 
after  section  of  the  posterior  nerve-roots  (Mott  and  Sherrington). 
We  can  hardly  suppose  that  in  any  case  the  trophic  influence  of  the 
cells  of  the  spinal  or  sympathetic  ganglia  to  which  all  other  reflex 
powers  have  been  denied,  is  of  reflex  nature.  And  there  is,  indeed, 
more  evidence  in  favour  of  trophic  tone  being  an  automatic  action 
of  the  cord  than  for  any  of  the  other  tonic  functions  hitherto  con- 
sidered. 

The  evidence  for  respiratory  automatism  upon  which  the  spinal 
cord  has  been  chiefly  credited  with  true  automatic  action  has  pre- 
viously been  given  (p.  278). 

The  *  Centres  '  of  the  Cord  and  Bulb. — We  have  frequently  used  the 
word  '  centre  '  in  describing  the  functions  of  the  spinal  cord,  but  the 
term,  although  a  convenient  one,  is  apt  to  convey  the  idea  that  our 
knowledge  is  far  more  minute  and  precise  than  it  really  is.  When  we 
say  that  a  centre  for  a  given  physiological  action  exists  in  a  definite 
portion  of  the  spinal  cord,  all  that  is  meant  is  that  the  action  can  be 
called  out  experimentally,  or  can  normally  go  on,  so  long  as  this  portion 
of  the  cord  and  the  nerves  coming  to  it  and  leaving  it  are  intact,  and 
that  destruction  of  the  '  centre  '  abolishes  the  action.  For  example,  a 
part  of  the  medulla  oblongata  on  each  side  cf  the  middle  line  in  the 
floor  of  the  fourth  ventricle  above  the  calamus  scriptorius  is  so  related 
to  the  function  of  respiration  that  when  it  is  destroyed  the  animal  ceases 
to  breathe.  But  this  respiratory  centre — the  '  noeud  vital '  of  Flourens 
— does  not  correspond  in  position  with  any  definite  collection  of  grey 
matter,  although  it  includes  the  nuclei  of  origin  of  several  cranial  nerves, 
and  forms  an  important  point  of  departure  for  efferent,  and  of  arrival 
for  afferent,  fibres  connected  with  the  respiratory  act.  Its  destruction 
involves  the  cutting  off  of  the  impulses  constantly  travelling  up  the 
vagus  to  modify  the  respiratory  rhythm,  and  of  the  impulses  constantly 
passing  down  the  cord  to  the  phrenics  and  the  intercostal  nerves.  And 
just  as  the  traffic  of  a  wide  region  can  be  paralyzed  at  a  single  blow  by 
severing  the  lines  in  the  neighbourhood  of  a  great  railway  junction,  or 
more  laboriously,  though  not  less  effectually,  by  separate  section  of  the 
same  tracks  at  a  radius  of  a  hundred  miles,  so  destruction  of  the 
respiratory  centre  accomplishes  by  a  single  puncture  what  can  be  also 
performed  by  section  of  all  the  respiratory  nerves  at  a  distance  from 
the  medulla  oblongata.  But  while  nobody  speaks  of  the  destruction  of 
a  '  centre  '  when  a  reflex  action  is  abolished  by  division  of  the  peripheral 
nerves  concerned  in  it,  there  is  a  tendency,  when  the  same  effect  is 
brought  about  by  a  lesion  in  the  brain  or  cord,  to  invoke  that  mysterious 
name,  and  to  forget  that  the  cerebro-spinal  axis  is  at  least  as  much  a 
stretch  of  conducting  paths  as  a  collection  of  discharging  nervous 
mechanisms. 

It  is,  perhaps,  a  profitless  task  to  enumerate  all  the  so-called  centres 
in  the  bulb  and  cord.  In  addition  to  the  great  vaso-motor,  respiratory, 
cardio-inhibitory  and  cardio-augmentor  centres  in  the  bulb,  which, 
perhaps,  ha\e  more  right  than  the  rest  to  be  regarded  as  distinct 
physiological  mechanisms,  if  not  as  definitely  bounded  anatomical 
areas,    there    have    been    distinguished   ano-spinal,   vesico-spinal,  and 


THE  CRANIAL  NERVES 


8fi 


gsnito-spinal  centres  in  the  lumbar  cofd,  a  oilio-spinal  centre  for  dic- 
tation of  the  pupil  in  the  cervical  cord,  and  in  the  medulla  centres  for 
sneezing,  for  coughing,  for  sweating,  for  sucking,  for  masticating,  for 
swallowing,  for  salivating,  for  vomiting,  for  the  production  of  general 
convulsions,  for  closure  of  the  eyes,  for  the  secretion  of  tears,  and  even  a 
'  diabetes  '  or  '  sugar  '  regulating  centre  (p.  538). 


Section  IX. — The  Cranial  Nerves. 

Unlike  the  spinal  nerves,  which  arise  at  not  very  unequal  intervals 
from  the  cord,  the  nuclei  of  the  cranial  nerves,  w-ith  the  exception 
of  the  olfactory  and  optic,  are  crowded  together  in  the  inch  or  two 
of  grey  matter  of  '.he 
primitive  neural  axis  in 
the  immediate  neigh- 
bourhood of  the  fourth 
ventricle  and  the  Syl- 
vian aqueduct.  Of  these 
nuclei  some  are  the  end 
nuclei  or  '  nuclei  of  re- 
ception '  of  sensory  fibres 
— that  is  to  say,  collec- 
tions of  nerve -cells 
around  which  the  sen- 
sory fibres  break  up  into 
terminal  arborizations. 
Such  are  the  sensory 
nuclei  of  the  fifth,  the 
nuclei  of  the  eighth,  and 
the  sensory  nuclei  of  the 
glossophar^Tigcal  and 
vagus  nerves  (Figs.  357, 
358).  The  nuclei  of  ori- 
gin of  the  motor  fibres 
lie,  upon  the  whole,  in 
two  longitudinal  rows — 
a  median  row,  which 
consists  of  the  nuclei  of 
the  third  and  fourth  nerves  in  the  floor  of  the  aqueduct,  and  those 
of  the  sixth  and  twelfth  nerves  in  the  floor  of  the  fourth  ven- 
tricle; and  a  lateral  row  comprising  the  motor  nuclei  of  the  fifth, 
seventh,  tenth,  and  eleventh  nerves.  The  clumps  of  grey  matter 
which  make  up  these  nuclei  may  be  considered  as  homologous  with 
the  grey  matter  of  the  ventral  or  anterior  (including  the  lateral) 
horn  of  the  spinal  cord ;  and  the  motor  fibres  of  the  nerves  themselves 
as  homologous  with  the  anterior  spinal  roots.  Without  going 
further  into  the  thorny  subject  of  the  homologies  of  the  cranial  and 


Fig.  357.— Nuclei  of  Cranial  Nerves  (Toldt).  Motor 
red,  sensory  blue.  The  numbers  correspond  to 
the  cranial  nerves. 


892 


THE  CENTRAL  NERVOUS  SYSTEM 


Spinal  nerves,  we  may  point  out  that  while  all  the  spinal  nerves 
contain  both  efferent  and  afferent  fibres,  some  of  the  cranial  nerves 
are  purely  efferent,  some  purely  afferent,  and  others  mixed.  So 
that  if  we  are  to  look  upon  the  motor  nerves  as  the  homologues  of 
the  ventral  roots,  the  dorsal  (posterior)  root-fibres  corresponding  to 
them  must  be  represented  in  the  other  cranial  nerves.     Thus,  the 


Fig.  358. — Nuclei  and  Roots  of  Cranial  Nerves  (Toldt). 

sensory  blue. 


Lateral  view.     Motor  red, 


sensory  portion  of  the  mixed  fifth  nerve,  and  the  purely  afferent 
auditory  nerve,  must  be  supposed  to  contain  fibres  corresponding 
to  several  dorsal  roots. 

The  first  or  olfactory  nerve  consists  of  fine  fibres,  each  of  which  is  a 
process  of  an  olfactory  cell  (Fig.  359).  The  olfactory  cells,  which  arc 
really  peripheral  nerve-cells,  lie  among  the  epithelial  cells  in  the  olfac- 
tory region  of  the  Schneiderian  membrane,  the  common  lining  of  the 
nostrils.  Each  olfactory  cell  gives  off  two  processes,  a  short  one, 
representing  a  dendrite,  which  runs  out  to  the  surface  of  the  mucous 
membrane,  and  a  longer  but  more  slender  process,  representing  an  axon. 


THE  CRANIAL  NERVES 


«93 


whicli  as  a  fibre  of  the  olfactory  nerve  pierces  the  cribriform  plate  of  the 
ethmoid  bone,  and  plunges  into  the  olfactory  bulb. 

In  the  olfactory  bulb  at  least  four  layers  can  be  distinguished — (i)  on 
the  surface,  beneath  the  pia  mater,  the  layer  cf  entering  olfactory 
ncrvc-fibres;  (2)  the  layer  of  olfactory  glomeruli,  peculiar  structures,  each 
of  which  is  made  up  of  an  intricate  basket-like  arborization  formed  by 
an  olfactory  nerve-fibre,  or,  it  may  be,  more  than  one,  and  a  brush-like 
arborization  belonging  to  a  dendrite  of  one  of  the  mitral  cells  of  the  next 
layer;  (3)  the  molecular  or  mitral  layer,  which  contains  a  number  of 
large  nerve-cells  called,  from  their  most  common  shape,  mitral  cells, 
along  with  smaller  nerve-cells  ('  granules  ')  and  neuroglia;  (4)  the  nuclear 
layer,  containing  numerous  small  nerve-cells  or  '  granules  '  intermingled 
with  white  fibres.  The  mitnil  cells  give  off  axons,  which  pass  through 
the  fourth  layer,  and  then  as  fibres  of  the  olfactory  tract  to  the  grey 
matter  of  the  hippocampal  region  of  the  brain.  The  course  of  the 
impulses  from  the  olfactory  mucous  membrane  to  the  brain  is  shown  in 
P^ff-  359-     The  olfactory  tract,  as  it  runs  back,  divides  into  portions 


Fig-  359-  —  Scheme  of  the  Olfactory  Nervous 
Apparatus  (Cajal).  A,  olfactory  cells;  B,  glomeruli; 
C,  mitral  cells;  1),  olfactory  granule  cell;  E,  lateral 
root  of  olfactory  tract;  F,  cortex  of  brain  in  the 
region  of  the  uncinate  gyrus;  a,  small  cell  of  mitral 
layer;  b,  brush  of  dendrite  of  a  mitral  cell  ending  in  a 
glomerulus;  c,  thorns  or  spines  on  the  processes  of  an  olfactory  granule;  e,  collateral 
coming  off  from  the  axon  of  a  mitral  cell;  /,  collaterals  ending  in  the  molecular  layer 
of  the  uncinate  gyrus;  g,  pyramidal  cells  of  the  cortex;  h,  supporting  epithelial  cells 
of  the  olfactory  mucous  membrane. 

called  its  '  roots.'  Of  these  the  lateral  is  the  most  important,  and  it 
terminates  in  the  hippocampal  and  uncinate  gyri  of  the  same  side. 
Fibres  of  the  olfactory  tract  are  also  connected  either  directly  or  through 
the  relay  of  another  neuron  with  the  opposite  side  of  the  brain,  especially 
the  opposite  uncinate  gyrus.  'J'he  anterior  comniissure  contains 
numerous  fibres,  which  connect  the  hippocampal  regions  of  the  two 
sides.  Other  central  connections  of  the  olfactory  tract  exist,  but  some 
are  imperfectly  known.  The  name  '  rhincncephalon  '  is  given  to  the 
portions  of  the  brain  concerned  with  the  sense  of  smell.  Disturbances 
of  smell  sensation  may  be  caused  by  lesions  in  any  part  of  the  rhincn- 
cephalon, and  also  by  changes  in  the  olfactory  mucous  membrane  and 
olfactory  fibres;  but  the  syniptoms  do  not  obtrude  themselves,  and  are 
doubtless  often  overlooked.  Excessive  stimulation  of  the  olfactory 
nerve  by  exposure  to  a  strong  odour  has  been  said  to  cause  complete 
and  permanent  los6  of  smell. 

The  second  or  optic  nerve  rontains  mainly  afferent  fibres,  which 
arise  from  tlie  ganglion  cells  of  the  retina,  and  terminate  by  forming 
synapses  wilh  nerve-cells  in  the  lateral  or  txlernal  geniculate  body,  the 


894 


THE  CENTRAL  NERVOUS  SYSTEM 


pulvinar  (or  posterior  portion)  of  the  optic  thalamus,  and  the  anterior 
corpus  quadrigcminum.  In  young  animals  all  these  structures  undergo 
atrophy  after  extirpation  of  the  eyeball.  The  visual  path  is  continued 
from  tiie  pulvinar  and  the  external  corpus  geniculatum  by  the  axons 
of  these  ner\'e-cells,  which  proceed  in  the  optic  radiation  (p.  855)  to  the 
occipital  cortex.  The  fibres  which  pass  from  the  retina  to  the  anterior 
corpus  quadrigcminum  are  distinguished  by  their  small  size,  and 
probably  constitute  the  path  of  the  impulses  which  cause  contraction 
of  the  pupil  when  light  falls  on  the  retina.  The  reflex  arc  is  schematic- 
allv  shown  in  Fig.  360,  where  optic  nerve-fibres  are  represented  as 
forming  synapses  with  cells  in  the  anterior  corpus  quadrigcminum 
whose  axons  pass  to  the  nucleus  of  the  third  nerve  and  arborize  around 

some  of  its  cells  (Figs.  344,  346, 
and  360).  At  the  chiasma  the 
fibres  of  the  optic  nerve  de- 
cussate, partially  in  man  and 
some  mammals,  as  the  rabbit, 
dog,  cat,  and  monkey,  com- 
pletely in  animals  whose  visual 
field  is  entirely  independent  for 
the  two  eyes,  as  in  fishes  and 
birds.  In  man  the  fibres  for 
the  nasal  halves  of  both  retinae 
cross  the  middle  line  at  the 
chiasma,  those  for  the  temporal 
halves  do  not.  This  does  not 
mean,  however,  that  exactly 
half  of  the  optic  nerve-fibres 
decussate.  The  number  of  un- 
crossed fibres  is  smaller  than 
that  of  crossed.  The  chiasma 
also  contains  fibres  in  its  pos- 
terior portion,  which  extend 
from  one  optic  tract  to  the 
other,  but  are  not  connected 
with  the  retinas  or  the  optic 
nerves.  They  are  commissural 
fibres  which  connect  the  two 
mesial  geniculate  bodies  across 
the  middle  line,  and  are  called 
Gudden's  commissure.  A  suffi- 
ciently extensive  lesion  involv- 
ing the  occipital  cortex  on  one 
side,  or  the  posterior  portion 
of  the  optic  thalamus,  or  the 
optic  tract,  causes  hemianopia*  or  defect  of  the  visual  field  on  the 
side  opposite  to  the  lesion,  with  blindness  of  the  corresponding  halves 
of  the  two  retinae.  Thus,  a  lesion  equivalent  to  complete  section  of  the 
right  optic  tract  would  cause  blindness  of  the  nasai  half  of  the  left,  and 
of  the  temporal  half  of  the  right  eye,  and  the  left  half  of  the  field  of 
vision  would  be  blotted  out — the  patient  would  be  unable,  with  his  eyes 
directed  forwards,  to  see  an  object  at  his  left.  Such  a  complete 
hemianopia  is  much  rarer  in  disease  of  the  cortex  than  in  disease  of  the 
*  The  terms  '  hemiopia,'  '  hemianopia,'  '  hemianopsia,'  are  used  with  refer- 
ence sometimes  to  the  blind  side  of  the  retinae,  but  ordinarily  to  the  half  of  the 
visual  field  which  i»  deficient  We  shall  always  use  the  word  '  hemianopia ' 
in  the  latter  sense. 


Fig.  360. — Scheme  of  the  Visual  Path  (after 
Schafer). 


THE  CRANIAL  NERVES  895 

optic  tract.  A  lesion — e.g..  a  tumour  of  the  pituitary  body — involvirig 
the  whole  of  the  optic  nerve  in  front  of  the  chiasma,  would  cause  com- 
plete blindness  in  the  corresponding  eye.  Sometimes  in  disease  of  the 
optic  nerve  vision  is  not  totally  destroyed  in  the  eye  to  which  it  belongs, 
but  the  field  is  narrowed  by  a  circumference  of  blindness.  In  this  case 
the  pathological  change  involves  the  circumferential  fibres  of  the  nerve. 
When  the  chiasma  is  affected  by  disease,  a  very  frequent  symptom  is 
bitemporal  hemianopia,  blindness  of  the  nasal  halves  of  the  retinae,  with 
loss  of  the  outer  cr  temporal  half  of  each  field  of  vision.  The  optic  nerve 
and  tract  contain  a  few  efferent  fibres  for  the  retina,  whose  cell-bodies 
have  not  yet  been  certainly  located. 

The  third  nerve,  or  oculo-motor,  arises  from  an  elongated  nucleus, 
or  a  series  of  nuclei,  containing  large  nerve-cells  in  the  floor  of  the 
Sylvian  aqueduct  below  the  anterior  corpora  quadrigemina.  The  root- 
bundles  coming  off  from  the  most  anterior  of  the  nuclei  carry  fibres  that 
innervate  the  ciliary  muscle,  and  thus  have  to  do  with  the  mechanism 
of  accommodation,  and  also  fibres  that  innervate  the  sphincter  muscle  of 
the  iris,  and  thus  cause  contraction  of  the  pupil  when  light  falls  on  the 
retina.  Both  groups  of  fibres  terminate  by  arborescing  around  sympa- 
thetic cells  in  the  ciliary  ganglion,  from  which  the  path  to  the  (unstriated) 
ciliary  and  sphincter  muscles  is  continued  by  post-ganglionic  fibres. 
Further  back  in  the  oculo-motor  nucleus  arisa  the  motor  fibres  for  four 
of  the  extrinsic  muscles  of  the  eyeball  and  th©  elevator  of  the  upper 
eyelid.  In  the  dog  these  fibres  come  off  in  the  following  order,  from 
before  backwards;  internal  rectus,  superior  rectus,  levator  palpebral 
superioris,  inferior  rectus,  inferior  oblique.  Most  of  the  fibres  of  the 
third  nerve  arise  from  nerve-cells  on  their  own  side  of  the  middle  line, 
but  a  certain  number  decussate  to  enter  the  nerve  of  the  opposite  side. 

Complete  paralysis  cf  the  third  nerve  causes  loss  of  the  power  of 
accommodation  of  the  corresponding  eye,  dilatation  of  the  pupil  by  the 
unopposed  action  of  the  sympathetic  fibres,  diminution  of  the  powder  of 
moving  the  eyeball,  ptosis,  or  drooping  of  the  upper  lid,  external  squint, 
and  consequent  diplopia,  or  double  vision. 

The  fourth  or  trochlear  nerve  arises  from  the  posterior  part  of  the 
same  tract  of  grey  matter  which  gives  origin  to  the  third  nerve.  It 
supplies  the  superior  oblique  muscle.  Paralysis  of  the  nerva  causes 
internal  squint  when  an  object  below  the  horizontal  plane  is  looked  at, 
owing  to  the  unopposed  action  of  the  inferior  rectus.  There  is  also 
diplopia  on  looking  down.  Unlike  the  other  cranial  nerves,  the  two 
trochlear  nerves  decussate  completely  after  they  emerge  from  their 
nuclei  of  origin. 

The  fifth  or  trigeminus  nerve  appears  on  the  surface  of  the  pons  as  a 
large  sensory  root  and  a  smaller  motor  root.  Its  deep  origin  is  more 
extensive  than  that  of  any  of  the  other  cerebral  nerves,  stretching  as  it 
does  from  the  level  of  the  anterior  corpus  quadrigeminum  above  to  the 
upper  part  of  the  spinal  cord  below.  Its  sensory  root,  in  fact,  seems  to 
include  the  sensory  divisions  of  several  motor  cranial  nerves. 

The  motor  root  arises  partly  from  a  nucleus  {principal  motor  nucleus) 
in  the  floor  of  the  fourth  ventricle  below  the  pons,  partly  from  large 
round  ncrve-cclls  lying  at  the  side  of  the  grey  matter  bounding  the 
aqueduct  of  Sylvius  all  the  wa}^  from  the  anterior  quadrigeminate  body 
to  the  point  at  which  the  motor  root  is  given  off  {aeccssory  or  superior 
motor  nucleus). 

The  fibres  of  the  sensory  root  have  their  cells  of  origin  in  the  Gasserian 
ganglion,  whence  they  pass  into  the  pons.  Here  they  bifurcate  into 
ascending  and  descending  branches.  The  ascending  branches  end  in 
the  principal  sensory  nucleus,  a  collection  of  grey  matter  at  the  side  of 


896 


THE  CENTRAL  NERVOUS  SYSTEM 


the  principal  motor  nucleus.  The  descending  branches,  turning  down- 
wards into  the  medulla  oblongata,  terminate  in  a  long  tract  of  scattered 
cells,  constituting  with  the  fibres  the  so-called  spinal  root,  and  extending 
from  the  level  of  the  second  cervical  nerve  through  the  medulla  oblon- 
gata and  the  pons,  where  it  is  continued  into  the  principal  sensory  nucleus. 
The  afferent  path  is  continued  by  the  axons 
of  cells  of  the  sensory  nuclei  (or  nuclei  of 
reception)  of  the  nerve,  many  of  which  cross 
the  middle  line  and  enter  the  intermediate 
fillet  of  the  opposite  side,  and  also  the 
special  ascending  bundle  going  to  the  thala- 
mus. Some  of  the  axons  do  not  decussate, 
bat  ascend  in  the  fillet  of  the  same  side. 


T,:  sp.  n.  r. 


Fig.  361. — Scheme  of  Motor  and  Sensory  Neurons  of  Trigeminus  (Gehuchten). 
G.  s.  G.,  Gasserian  ganglion;  Nu.  m.  m.  n.  V.,  nucleus  of  the  descending  root; 
Nu.  m.  pr.  n.  V .,  chief  motor  nucleus  of  the  fifth  nerve;  Rad.  desc.  mes.  n.  V ., 
accessory  motor  nucleus,  sometimes  called  the  descending  root;  Tr,  sp.  n.  V ., 
tractus  spinalis,  or  spinal  root  of  the  fifth. 

The  motor  fibres  of  the  fifth  nerve  supply  the  muscles  of  mastication 
and  the  tensor  tympani.  The  sensory  fibres  confer  common  sensation 
on  the  face,  conjunctiva,  the  mucous  membranes  of  the  mouth  and  nose, 
and  the  structures  contained  in  them,  and,  according  to  Gowers,  special 
sensation,  through  branches  given  off  to  the  facial  and  glosso-pharyngeal 
nerves,  on  the  organs  of  taste.*     Complete  paralysis  of  the  nerve  causes 

*  It  should  be  stated  that  some  physiologists  believe  that  the  glosso-pharyn- 
geal is  the  nerve  of  taste,  and  that  none  of  the  taste  fibres  go  to  the  sensory 
nuclei  of  the  fifth  nerve.  The  majority  hold  that  the  glosso-pharyngeal 
supplies  the  posterior  third,  and  the  chorda  tympani  and  lingual  the  anterior 
two-thirds  of  the  tongue  with  gustatory  fibres.  The  removal  of  the  Gasserian 
ganglion  and  the  adjacent  portion  of  the  fifth  nerve  for  severe  and  persistent 
neuralgia,  has  afforded  opportunities  to  test  this  question.  But,  unfortunately 
the  results  described  by  various  observers  do  not  agree,  some  finding  that 
taste  is  unimpaired,  others  that  it  is  abolished.  Gowers  states  that  the  gus- 
tatory sensations  may  persist  for  some  time  after  the  operation,  although 
ultimately  (in  tw'o  or  three  weeks)  they  disappear.  It  may  be,  however,  that 
this  disappearance  is  due  to  secondary  changes  produced  in  the  end-organs 
of  the  true  taste  fibres,  the  taste  buds,  by  degeneration  of  the  supporting  cells 
consequent  on  section  of  the  trigeminus,  or  to  degeneration  and  swelling  of 
the  trigeminal  fibres  in  the  lingual  nerve  and  consequent  interference  with 
the  conductivity  of  the  intermingled  chorda  tympani  fibres.     Gushing  believes 


THE  CRANIAL  NERVES  897 

loss  of  movement  in  the  muscles  of  mastication,  sometimes  impaired 
hearing,  artd  loss  of  common  sensation  in  the  area  supplied  by  it.  Loss 
or  impairment  of  taste  in  the  corresponding  half  of  the  tongue  is  also 
often  seen  in  disease  involving  the  sensory  root,  although  not  in 
affections  of  the  trunk  of  the  nerve,  since  the  taste  fibres  leave  it  near 
its  origin  (Gowers).  Both  taste  and  touch  are  lost  in  the  monkey  in  the 
anterior  two-thirds  of  the  tongue  after  intracranial  section  of  the 
trigeminus  (Sherrington). 

Vaso-motor  changes  are  occasionally,  and  '  trophic  '  changes  fre- 
quently, observed  in  disease  of  the  fifth  nerve.  The  trophic  disturbance 
is  most  conspicuous  in  the  eyeball  (ulceration  of  the  cornea,  going  on. 
it  may  be,  to  complete  disorganization  of  the  eye).  These  effects  are 
partly  due  to  the  loss  of  sensation  in  the  eye,  and  the  consequent  risk  of 
damage  from  without,  and  the  unregarded  presence  of  foreign  bodies 
and  accumulation  of  secretion  within  the  lids  (p.  778). 

The  sixth  or  abducens  nerve  takes  origin  from  a  nucleus  in  the  floor 
of  the  fourth  ventricle  at  the  level  of  the  posterior  portion  of  the  pons. 
It  is  a  purely  efferent  nerve,  and  supplies  the  external  rectus  muscle 
of  the  eyeball.     Paralysis  of  it  causes  internal  squint. 

The  motor  fibres  of  the  seventh  or  facial  nerve  arise  from  a  nucleus 
in  the  reticular  formation  of  the  medulla  oblongata,  and  running  up 
some  distance  into  the  pons.  They  supply  the  muscles  of  the  face;  and 
when  these  are  greatly  developed,  as  in  the  trunk  of  the  elephant,  the 
nerve  reaches  vet}-  large  proportions.  Since  the  fibres  which  connect 
the  cerebral  cortex  with  the  nucleus  decussate  about  the  middle  of  the 
pons,  a  lesion  above  this  level  which  causes  hemiplegia  paralyzes  the 
face  on  the  same  side  as  the  rest  of  the  body — i.e.,  on  the  side  opposite 
the  lesion.  But  the  paralysis  is  confined  to  the  muscles  of  the  lower 
portion  of  the  face,  and  aftects  especially  the  muscles  about  the  mouth. 
Sometimes  the  pyramidal  tract  and  the  facial  nerve,  or  nucleus,  are 
involved  in  a  common  lesion.  In  this  case  paralysis  of  the  face  is  on 
the  side  of  the  lesion,  and  is  total,  while  the  rest  of  the  body  is  para- 
lyzed on  the  opposite  side.  Paralysis  of  the  seventh  nerve  is  more 
common  than  that  of  any  other  nerve  in  the  body.  It  is  often  caused 
by  an  inflammatory  process  in  the  nerve  itself  (neuritis).  The  symp- 
toms of  complete  facial  palsy  are  very  characteristic.  The  face  and 
forehead  on  the  paralyzed  side  are  smooth,  motionless,  and  devoid  oi 
expression.  The  eye  remains  open  even  in  sleep,  owing  to  paralysis 
of  the  orbicularis  palpebrarum.  A  smile  becomes  a  grimace.  An 
attempt  to  wink  with  both  eyes  results  in  a  grotesque  contortion.  The 
mouth  appears  like  a  diagonal  slit  in  the  face,  its  angle  being  drawn 
up  on  the  sound  side,  and  the  patient  cannot  bring  the  lips  sufficiently 
close  together  to  be  able  to  blow  out  a  candle  or  to  whistle.  Liquids 
escape  from  the  mouth,  and  food  collects  between  the  paralyzed  buc- 
cinator and  the  teeth.  The  labial  consonants  are  not  properly  pro- 
nounced. Taste  may  be  lost  in  the  anterior  two-thirds  of  the  tongue 
when  the  nerve  is  injured  above  the  exit  of  the  gustatory  fibres  in  the 
chorda  tympani,  but  not  when  the  lesion  is  in  the  nucleus  of  origin,  or 
anywhere  above  it.  Hearing  is  sometimes  impaired  because  the 
auditor)'  and  facial  nerves,  lying  close  together  for  part  of  their  course, 
are  apt  to  suffer  together,  but  perhaps  also  because  the  stapedius 
muscle  is  supplied  by  the  seventh. 

that  the  fifth  nerve  sui)i)lieb  no  taste  fibres,  but  that  the  taste  fibres  for  the 
anterior  two-thirds  of  the  tongue  have  their  cells  of  origin  in  the  geniculate 
ganglion  of  the  pars  intermedia  of  the  seventh  nerve,  and  those  for  the  pos- 
terior third  in  the  ganglion  petrosum  of  the  ninth  nerve. 

57 


SgS 


THE  CENTRAL  NERVOUS  SYSTEM 


The  seventh  nerve  is  not  purely  motor.  From  the  cells  of  a  ganglion 
on  it  corresponding  to  a  spinal  ganglion  (the  geniculate  ganglion) 
afferent  fibres  arise,  which  pass  in  the  pars  intermedia  or  nerve  of 
Wrisberg  into  the  pons  between  the  seventh  and  eighth  nerves,  and 
there  bifurcate  into  ascending  and  descending  branches,  like  other 
afferent  fibres  originating  in  ganglia  of  the  spinal  type.  The  descend- 
ing branches  enter  the  fasciculus  solitarius,  and  end  by  arborizing 
around  nerve-cells  in  the  upper  part  of  that  bundle.  The  peripheral 
axons  of  the  nerve-cells  in  the  geniculate  ganglion  enter  the  large  super- 
ficial petrosal  nerve  and  the  chorda  tympani,  in  which  they,  or  some 
of  them,  perhaps  represent  taste  fibres. 

The  eighth  or  auditory  nerve  enters  the  medulla  oblongata  by  two 
roots  (a  dorsal  and  a  ventral),  one  of  which  passes  in  on  each  side  of 


vin 


Fig.  362. — Scheme  of  Path  of  Auditory  Impulses  (Lewandowsky).  Sp,  ganglion 
spirale;  G,  accessory  nucleus;  T,  acoustic  tubercle;  Tr,  trapezium;  H,  Held's 
fibres;  St,  striae  acusticae;  tr,  trapezoid  nucleus;  Os,  upper  olive;  LI,  lateral  fillet, 
with  its  nucleus,  nL;  P,  commissure  of  the  lateral  fillets;  Qp,  posterior  corpora 
quadrigemina,  with  Cq,  their  comiuissure,  and  Bq,  the  brachia;  Gm,  mesial  or 
internal  geniculate  body;  R,  cerebral  cortex. 

the  restiform  body.  The  cells  of  origin,  both  of  the  dorsal  and  of  the 
ventral  root,  are  situated  in  the  internal  ear,  the  former  in  the  ganglion 
spirale,  or  ganglion  of  Corti,  which  is  embedded  in  the  bony  spiral  of 
the  cochlea,  the  latter  in  the  ganglion  vestibulare,  or  ganglion  of  Scarpa, 
which  lies  in  the  vestibule.  These  cells  correspond  to  the  ganglion 
cells  on  the  posterior  root  of  a  spinal  nerve,  but,  unlike  them,  they 
remain,  even  in  mammals,  bipolar  throughout  life.  Their  central 
processes  form  the  axons  of  the  eighth  nerve.  Their  peripheral  pro- 
cesses are  distributed  in  the  case  of  the  dorsal  root  to  the  organ  of 
Corti,  in  the  case  of  the  ventral  root  to  the  semicircular  canals  and  the 
vestibule.  For  this  reason  the  dorsal  root  is  often  called  the  cochlear 
division,  and  the  ventral  root  the  vestibular  division  of  the  auditorv 


THE  CRANIAL  NERVES  899 

nerve.  And  the  cochlear  and  vestibular  roots  arc  physiologically 
as  well  as  anatomically  distinct.  For  the  cochlea  sul»ervcs  the 
function  of  hearing,  the  semicircular  canals  and  vestiljule  the  function 
of  equilibration.  As  they  enter  the  medulla  oblongata,  the  fibres  of 
the  dorsal  root  bifurcate.  Of  the  two  branches,  one  is  considerably 
thicker  than  the  other.  Many  of  the  thicker  branches  terminate  by 
arborizing  around  the  cells  of  the  accessory  auditory-  nucleus,  whose 
position  is  indicated  by  a  swelling  on  the  ventral  surface  of  the  resti- 
form  body  at  the  junction  of  the  dorsal  and  ventral  roots;  but  some 
pass  over  the  restiform  body  to  end  in  another  nucleus  (lateral  nucleus), 
also  indicated  by  a  swelling  (tuberculura  acusticum)  lying  over  the 
restiform  body.  The  nerve-cells  of  the  accessory  nucleus  and  the 
acoustic  tubercle,  therefore,  constitute  nuclei  of  reception  for  the 
dorsal  root-fibres.  The  more  slender  branches  of  the  cochlear  root- 
fibres  run  downwards  for  some  distance  before  breaking  up  into  fibrils. 

The  path  to  the  higher  parts  of  the  brain  is  continued  by  the  axons 
of  nerve-cells  in  the  accessory  nucleus  and  the  acoustic  tubercle.  The 
fibres  from  the  accessory  nucleus  pass  into  the  trapezium,  a  mass  of 
transverse  fibres  lying  in  the  pons  behind  the  pyramidal  fibres.  In 
their  course  through  the  trapezium  some  of  the  fibres  terminate  around 
the  cells  of  the  nucleus  of  the  trapezium,  others  run  into  the  superior 
olive  of  the  same  side,  and  end  there ;  but  most  of  them  cross  the  middle 
line,  and  enter  the  trapezoid  nucleus  and  superior  olive  of  the  opposite 
side,  where  many  of  them  terminate.  Others,  however,  run  through 
those  nuclei  and  pass  into  the  lateral  fillet,  to  end  in  its  nucleus  or  in, 
the  posterior  corpora  quadrigemina.  The  path  of  the  fibres  wliich 
terminate  in  the  nuclei  of  the  trapezium,  superior  olive,  and  lateral 
fillet,  is  continued  by  another  relay  of  fibres,  which  link  them  also  to 
the  posterior  corpora  quadrigemina.  The  axons  of  the  cells  of  the 
acoustic  tubercle  enter  for  the  most  part  the  stricB  acusticcs,  a  series  of 
prominent  strands  that  run  transversely  across  the  floor  of  the  fourth 
ventricle.  Passing  across  the  raphe,  they  join  the  fibres  from  the 
accessory  nucleus  on  their  way  to  the  superior  olive,  and  accompany 
them  into  the  lateral  fillet,  which  terminates  in  the  grey  matter  of  the 
posterior  corpus  quadrigeminum.  We  must  assume,  from  clinical  and 
experimental  data,  that  the  dorsal  root  is  ultimately  connected  with 
the  first  or  first  and  second  temporo-sphenoidal  convolutions  on  the 
opposite  side.  From  the  posterior  corpora  quadrigemina  the  auditory 
path  to  the  convolutions  seems  to  run  in  the  brachium  to  the  internal 
or  mesial  geniculate  body,  whence  it  is  continued  in  the  posterior 
extremity  of  the  internal  capsule. 

The  fibres  of  the  ventral  root  of  the  eighth  nerve,  better  termed  the 
vestibular  nerve,  after  entering  the  medulla  oblongata,  pass  to  a 
nucleus  called  the  principal  nucleus  of  the  vestibular  division.  Here 
each  bifurcates  into  a  descending  and  an  ascending  branch.  The 
descending  branches  running  down  in  the  medulla  terminate  at  dif- 
ferent levels  around  cells  in  the  principal  nucleus,  and  the  grey  matter 
continued  down  from  it  {descendivg  vestibular  nucleus).  The  ascending 
branches  run  up  on  the  inner  side  of  the  restiform  body  towards  the 
nucleus  of  the  roof  (nucleus  tecti)  in  the  cerebellar  worm.  Oil  their 
course  they  enter  into  relation  through  their  collaterals  with  the  nuclei 
of  Deiters  and  Beciiterew.  The  nucleus  of  Deiters,  as  already  stated, 
sends  fibres  into  tlie  posterior  longit  udinal  bundle.  '1  hrough  ascend- 
ing branches  of  these  fibres  a  communication  is  established  with  ihe 
nuclei  of  the  third  and  sixtii  nerves,  and  through  descending  branches 
that  pass  into  the  antero-lateral  descending  tract  of  the  cord  with  the 
anterior   horn   cells.     It   is   obvious   that   tiirough   these   connections 


900  THE  CENTRAL  NERVOUS  SYSTEM 

which  link  the  vestibule  with  the  cerebellum,  the  nuclei  of  the  motor 
nerves  of  the  eyeball  and  the  motor  cells  of  the  cord,  the  nucleus  of 
Deiters  has  an  important  relation  to  the  co-ordination  of  those  move- 
ments mainly  concerned  in  equilibration.  Nothing  is  known  of  the 
connections  of  the  vestibular  nerve  with  the  cerebrum.  Two  promi- 
nent symptoms  may  be  associated  with  disease  of  the  auditory  nerve — 
(rt)  disturbance  or  loss  of  hearing ;  {b)  loss  or  impairment  of  equilibration. 

The  ninth  or  glosso-pharyngeal  nerve  comprises  both  sensory  and 
motor  fibres — sensory  for  the  posterior  third  of  the  tongue  and  the 
mucous  membrane  of  the  back  of  the  mouth,  motor  for  the  middle 
constrictor  of  the  pharynx  and  the  stylo-pharyngeus.  It  also  contains 
the  nerves  of  taste  for  the  posterior  third  of  the  tongue.  The  efferent 
fibres  arise  from  a  nucleus  (motor  nucleus  of  the  glosso-pharyngeal)  a 
little  posterior  to  the  facial  nucleus.  The  afferent  fibres  take  origin 
from  unipolar  cells  in  ganglia  of  spinal  type  connected  with  the  nerve 
(ganglion  petrosum  and  ganglion  superius).  Entering  the  medulla 
oblongata,  the  central  processes  of  these  cells  bifurcate  into  ascending 
and  descending  branches.  Their  peripheral  processes  pursue  their 
course  as  the  axons  of  sensory  fibres  to  the  structures  to  which  the 
nerve  is  distributed.  The  ascending  branches  terminate  in  a  nucleus 
{principal  nucleus  of  the  glosso  -  pharyngeal)  beneath  the  floor  of  the 
fourth  ventricle.  The  descending  branches,  as  well  as  similar  branches 
from  the  pars  intermedia  of  the  seventh  nerve  and  from  the  afferent 
fibres  of  the  vagus,  form  a  bundle  called  the  fasciculus  solitarius  (some- 
•  times  termed  the  descending  root  of  the  facial,  vagus,  and  glosso-pharyn- 
geal). It  can  be  traced  to  the  lower  boundary  of  the  spinal  bulb. 
Along  the  mesial  border  of  the  fasciculus  solitarius  are  strung  out  the 
somewhat  scattered  nerve-cells  [descending  nucleus  of  facial,  vagus,  and 
glosso-pharyngeal),  around  which  the  descending  branches  arborize. 
At  its  upper  end  the  grey  matter  of  the  fasciculus  solitarius  is  con- 
tinuous with  the  principal  nuclei  of  the  glosso-pharyngeal  and  vagus. 

The  tenth  nerve,  or  vagus,  also  contains  both  motor  and  sensory 
fibres.  The  efferent  fibres  arise  partly  from  the  nucleus  ambiguus  or 
ventral  nucleus  of  the  vagus,  a  collection  of  large  nerve-cells  situated  in 
the  reticular  formation,  and  extending  from  a  point  a  little  below  the 
facial  nucleus  to  a  point  a  little  above  the  lower  limit  of  the  medulla 
oblongata,  where  it  becomes  continuous  with  the  column  of  cells  from 
which  the  spinal  fibres  of  the  eleventh  nerve  take  origin.  A  second 
nucleus  of  origin  for  efferent  vagus  fibres  is  constituted  by  the  upper 
part  of  the  dorsal  accessory-vagus  nucleus,  a  collection  of  rather  small 
cells  extending  from  a  little  below  the  lower  margin  of  the  pons  to 
nearly  the  level  of  tlie  first  cervical  nerve. 

The  afferent  fibres  of  the  vagus  arise  from  unipolar  cells  in  ganglia 
connected  with  the  nerve  (ganglion  jugulare,  ganglion  nodosum).  In 
the  medulla  oblongata  they  bifurcate,  like  other  fibres  coming  off  from 
the  cells  of  ganglia  of  spinal  type.  The  ascending  branches,  which  are 
short,  terminate  in  the  upper  sensory  or  principal  nucleus,  and  the. 
descending  branches,  which  are  long,  in  the  cells  of  the  fasciculus  soli- 
tarius, just  as  in  the  case  of  the  glosso-pharyngeus. 

The  motor  fibres  of  the  vagus  are  partly  derived  from  the  accessory, 
whose  internal  branch  joins  the  vagus  not  far  from  its  origin.  The 
distribution  of  the  nerve  is  more  extensive  than  that  of  any  other  in 
the  body.  The  oesophagus  receives  both  motor  and  sensory  branches 
from  the  oesophageal  plexus.  The  pharyngeal  branch  of  the  vagus  is 
the  chief  motor  nerve  of  the  pharynx  and  soft  palate  (including  the 
tensor  palati).  The  sujierior  laryngeal  branch  is  the  nerve  of  common 
sensation  for  the  larynx  above  the  vocal  cords,  and  the  motor  nerve 


THE  CRANIAL  NERVES  90T 

of  the  crico-thyroid  muscle.  The  inferior  or  recurrent  laryngeal  sup- 
plies the  rest  of  the  laryngeal  muscles,  and  the  sensory  fibres  for  the 
mucous  membrane  of  the  trachea  and  the  larynx  below  the  glottis. 
The  superior  laryngeal  contains  afferent  fibres,  stimulation  of  which 
gives  rise  to  coughing,  slows  respiration,  or  stops  it  in  expiration. 
Reflex  movements  of  deglutition  are  also  caused.  The  vagus  supplies 
the  lungs  both  with  motor  and  sensory  filaments  through  the  pulmonary 
plexus.  The  motor  fibres  when  stimulated  cause  constriction  of  the 
bronchi;  excitation  of  the  afferent  fibres  causes  reflex  changes  in  the 
rate  or  depth  of  respiration.  The  cardiac  branches  contain  inhibitory 
fibres  probably  derived  from  the  spinal  accessory,  and  depressor  fibres 
which  pass  up  in  the  vagus  trunk  (dog),  or  as  a  separate  nerve  to  join 
the  vagus  or  its  superior  laiymgeal  branch  or  both  (rabbit).  The  gastric 
and  intestinal  branches  contain  both  motor  and  sensory  nerves  for  the 
stomach  and  intestines.  The  sensory  are  probably  large  meduUated 
fibres  (7  A*  to  9  ^).  The  afferent  vagus  fibres  from  the  stomach  carry 
up  impulses  which  excite  the  action  of  vomiting.  Lesions  of  the  vagus, 
its  nuclei  of  origin,  or  its  branches,  are  associated  with  many  interest- 
ing forms  of  paralysis  and  other  symptoms.  Paralysis  of  the  pharynx 
is  generally  caused  by  disease  of  the  nucleus  in  the  medulla.  From  its 
anatomical  relation  to  the  nuclei  of  the  glosso-pharyngeal  and  hypo- 
glossal, it  will  be  easily  understood  that  these  nerves  are  often  involved 
in  localized  central  lesions  along  with  the  vagus.  But  the  fact  that  in 
progressive  bulbar  palsy  (glosso-labio-laryngeal  paralysis) — a  condition 
characterized  by  progressive  paralysis  and  atrophy  of  the  muscles  of 
the  tongue,  lips,  larynx,  and  pharynx — the  orbicularis  oris  and  other 
muscles  of  the  mouth  and  chin  are  paralyzed,  while  the  rest  of  the 
muscles  supplied  by  the  facial  remain  intact,  might  seem  to  indicate 
that  in  system  diseases  it  is  not  so  much  anatomical  groups  of  nerve- 
cells  which  are  liable  to  simultaneous  degeneration  and  failure,  as 
physiological  groups  normally  associated  in  particular  functions.  Such 
functional  groups  of  cells,  occupied  with  the  same  kinds  of  labour  at 
the  same  times  and  under  the  same  conditions,  might  be  supposed  to 
take  on  a  similar  bias  or  tendency  to  degeneration — a  tendency  not 
indicated,  it  may  be,  by  any  structural  peculiarity,  but  traced  deep  in 
the  molecular  activity  of  the  cells.  There  is  no  foundation  for  the 
view  that  the  lips  are  involved  in  progressive  bulbar  palsy  because  the 
fibres  of  the  facial  which  supply  them  arise  from  the  hypoglossal 
nucleus,  any  more  than  for  the  idea  that  the  upper  part  of  the  face 
escapes  because  its  motor  fibres,  while  reaching  it  in  the  seventh  nerve, 
really  arise  from  the  oculo-motor  nucleus  (Bruce).  Difficulty  in  swal- 
lowing is  the  chief  symptom  of  pharyngeal  paralysis.  The  symptoms 
of  laryngeal  paralysis  have  been  already  described  under  '  Voice  ' 
(p.  310).  Tachycardia,  or  a  permanent  increase  in  the  rate  of  the 
heart,  has  been  stated  to  occur  in  certain  cases  of  paralysis  of  the 
vagus,  caused  by  disease  or  accidental  interference;  and  a  persistent 
s-lowing  of  the  respiration  has  been  occasionally  attributed  to  the  same 
cause.  But  it  is  difficult  to  reconcile  many  of  these  cases  with  experi- 
mental results,  for  in  most  of  them  the  lesion  only  involved  one  vagus ; 
and  in  animals  section  of  one  vagus  has  no  permanent  effect  on  the 
rate  of  the  heart  or  of  the  respiratory  movements. 

Destruction  of  the  nerve  near  its  origin  has  been  sometimes  found 
associated  with  disappearance  of  the  food-appetites,  hunger  and  thirst, 
and  it  has  been  assumed  that  this  was  due  to  lo.ss  of  afferent  impulses 
from  the  stomach.  But  clinical  testimony  is  by  no  means  unanimous 
on  this  point,  and  experiments  on  animals  show  that  other  factors  are 
involved  in  these  sensations  (see  Chapter  XVI II.). 


902  THE  CENTRAL  NERVOUS  SYSTEM 

The  eleventh  or  spinal-accessory  nerve  contains  only  efferent  fibres. 
The  cells  of  origin  of  its  spinal  portion  lie  in  the  lateral  horn  of  the 
cord,  from  about  the  level  of  the  first  to  the  fifth  or  sixth  cervical 
nerves.  The  bulbar  portion,  sometimes  called  the  bulbar  accessory, 
arises  from  the  lower  two-thirds  of  the  dorsal  accessory-vagus  nucleus, 
from  about  the  level  of  the  first  cervical  nerve  up  to  the  level  of  the 
tip  of  the  calamus  script(?rius.  The  accessory  portion  of  the  nucleus 
lies  behind  and  to  the  side  of — i.e.,  dorso-lateral  to — the  central  canal; 
the  upper  or  vagus  portion  is  more  laterally  placed  in  the  floor  of  the 
fourth  ventricle.  Soon  after  the  junction  of  its  bulbar  and  spinal 
portions,  the  nerve  divides  into  two  branches,  an  internal  and  an 
external.  The  external  branch,  containing  the  spinal  fibres,  passes  out 
to  supply  the  trapezius  and  sterno-mastoid  muscles  with  motor  fibres. 
The  internal  branch,  containing  the  bulbar  fibres,  passes  bodily  into 
the  vagus. 

The  twelfth  or  hypoglossal  nerve  is  exclusively  an  efferent  nerve. 
Its  nucleus  of  origin  is  an  elongated  collection  of  large  nerve-cells  ex- 
tending throughout  approximately  the  lower  two-thirds  of  the  bulb 
close  to  the  median  line  and  parallel  to  it.  It  contains  the  motor 
supply  of  the  intrinsic  and  extrinsic  muscles  of  the  tongue  and  of  the 
thyro-  and  genio-hyoid.  Paralysis  of  it  causes  deficient  movement  of 
the  corresponding  half  of  the  tongue.  When  the  tongue  is  put  out,  it 
deviates  towards  the  paralyzed  side,  being  pushed  over  by  the  un- 
paralyzed  genio-hyoglossus  of  the  opposite  side,  which  is  thrown  into 
action  in  protruding  the  tongue. 

Section   X. — Functions  of  the  Central  Nervous   System  — 

(2)  The  Brain. 

The  paths  by  which  the  various  parts  of  the  central  nervous 
system  are  connected  with  each  other  and  with  the  periphery  have 
been  already  described,  and  we  have  completed  the  examination  of 
the  functions  of  the  spinal  cord  and  medulla  oblongata.  The 
events  that  take  place  in  the  upper  part  of  the  central  nervous 
stem  and  in  the  cortex  of  the  cerebellum  and  cerebrum  now  claim 
our  attention. 

From  very  early  times  the  brain  has  been  popularly  believed  to  be 
the  seat  of  all  that  we  mean  by  consciousness — sensation,  ideation, 
emotion,  volition.  And  he  who  loves  to  trace  the  roots  of  things  back 
into  the  past  may  see,  if  he  choose,  running  through  the  whole  texture 
of  the  older  speculations  a  belief  that  the  brain  does  not  act  as  a  whole, 
but  is  divided  into  mechanisms,  each  with  its  special  work — a  fore- 
shadowing, often  in  grotesque  outlines,  of  the  doctrine  of  localization 
so  widely  held  to-day.  But  until  comparatively  recent  times,  cerebral 
physiology  remained  a  kind  of  scientific  terra  incognita;  and  no  notable 
additions  were  made  for  a  thousand  years  to  the  doctrines  of  Galen. 
Even  to-day  the  utmost  limit  of  our  knowledge  is  reached  when  in 
certain  cases  we  have  connected  a  particular  movement  or  sensation 
with  a  more  or  less  sharply-defined  anatomical  area.  How  the  cere- 
bral processes  that  lead  to  sensations  and  movements,  to  emotions  and 
intellectual  acts,  arise  and  die  out;  what  molecular  changes  are  asso- 
ciated with  them;  above  all,  how  the  molecular  changes  are  translated 
into  consciousness — how,  for  example,  it  is  that  a  series  of  nerve- 
impulses  from  the  optic  radiation  flickering  across  the  labyrinth  of  the 


FUNCTIONS  OF  THE  BRAIN  903 

occipital  cortex  should  light  up  there  a  visual  sensation — these  are 
questions  tc  which  we  can  as  yet  give  no  answer,  and  the  answers  to 
some  of  whicli  must  for  ever  remain  liidden  from  us. 

Functions  of  the  Upper  Part  of  the  Central  Stem  and  Basal  Ganglia. 
— Tlie  function  f)f  tin-  pons  is  suKicicntly  iiuliciiled  l>y  its  name.  The 
grey  matter  so  plentifully  scattered,  especially  in  its  ventral  portion, 
may  exercise  a  not  unimportant  influence  on  the  impulses  that  traverse 
it.  But  on  the  whole  its  main  office  is  to  provide  a  bridge  along  which 
impulses  may  travel  between  other  portions  of  the  nervous  system. 
We  have  already  seen  that  many  of  its  transverse  fibres  arising  from 
the  cells  of  the  pontine  grey  matter,  and  then  crossing  the  middle  line 
to  the  opposite  middle  peduncle,  are  the  cerebellar  segments  of  com- 
missural arcs  connecting  the  cerebral  with  the  opposite  cerebellar 
hemispheres.  ,  The  cerebral  segments  of  these  arcs  are  the  cortico- 
pontine fibres  originating  in  the  prefrontal,  temporal,  and  occipital 
portions  of  the  cerebral  cortex,  and  passing  through  the  corona  radiata, 
internal  capsule,  and  crura  cerebri,  to  end  in  the  nuclei  pontis.  Many 
fibres  and  collaterals  of  the  pyramidal  tract  also  terminate  here.  On 
the  dorsal  aspect  of  the  pons  in  the  floor  of  the  fourth  ventricle  are  the 
nuclei  of  origin  (or  reception)  of  the  fifth,  sixth,  and  seventh  cranial 
nerves.  Various  reflex  centres  are  situated  in  this  region — e.g.,  that 
for  the  closure  of  the  eyelids,  when  the  conjunctiva  is  stimulated. 

The  posterior  corpora  quadrigemina  and  internal  geniculate  bodies  are 
connected  with  the  cochlear  division  of  the  auditory  nerves,  and  form 
important  stations  on  the  auditory  path  to  the  cortex. 

The  anterior  corpora  quadrigemina  and  the  lateral  corpora  geniculata 
are  connected  with  the  optic  tracts.  Their  development  is  arrested 
after  extirpation  of  the  eyeball  in  young  animals,  and  they  may  there- 
fore be  assumed  to  be  concerned  in  vision,  although  the  size  of  their 
homologues,  the  optic  lobes  or  corpora  bigemina,  in  animals  below  the 
rank  of  mammals  (birds,  reptiles,  amphibians),  does  not  seem  to  be 
related  to  the  development  of  the  organs  of  sight.  Proteus  and  the 
Hag-fish,  e.g.,  have  large  optic  lobes,  rudimentary'  eyes  and  optic  tracts. 
The  optic  nerve,  the  anterior  corpus  quadrigeminum,  the  nucleus  of  the 
oculo-motor  nerve  in  the  wall  of  the  Sylvian  acjueduct,  and  the  fibres 
which  it  carries  to  the  iris,  form  a  reflex  arc  for  the  contraction  of  the 
pupil  to  light,  as  represented  in  Fig.  360,  p.  894. 

The  funciions  of  the  optic  ihalami  have  not  been  fully  defined  either 
by  experiment  or  pathological  observation,  except  in  so  far  as  they  can 
be  deduced  from  their  connections.  Lying  as  they  do  in  the  isthmus 
of  the  brain,  begirt  by  the  great  motor  and  sensory  paths,  it  is  to  be 
expected  that  lesions  of  the  thalami  should  affect  also  the  internal 
capsule,  and  give  rise  to  the  symptoms  of  motor  and  sensory  paralysis. 
But  it  is  questionable  whether  any  definite  defect  of  motor  power  or 
common  sensation  has  ever  been  unequivocally  associated  with  a  lesion 
restricted  to  the  thalami.  The  most  constant  features  of  the  so-called 
thalamic  syndrome  (or  symptom-complex)  arc  partial  loss  of  sensibility, 
especially  to  tactile  impressions,  and  of  the  muscular  sense  on  the 
opposite  side,  with  some  degree  of  inco-ordi nation  and  disorder,  though 
little,  if  any,  actual  paralysis  of  voluntary-  movements.  These  phe- 
nomena are  accounted  for  by  the  extensive  connections  of  the  thalami. 
Each  of  the  thalamic  nuclei  is  linked  with  a  definite  cortical  region  in 
sucji  a  way  that  destruction  of  the  cortical  area  in  young  animals  or 
human  beings  leads*  to  degeneration  of  the  corresponding  nucleus. 
Some  of  the  fibres  connecting  the  cortex  (and  the  corpus  striatum) 
with  the  thalamus  end  in  the  thalamic  grey  matter,  and  are  therefore 
efferent  with  respect  to  the  cortex  (corticofugal).     It  is,  however,  the 


904  THE  CENTRAL  NERVOUS  SYSTEM 

afferent  paths  to  the  cortex  with  which  the  thalami  are  specially  related 
as  centres  of  relay.  The  fibres  of  the  upper  fillet  carrying  afferent  im- 
pulses up  from  the  opposite  posterior  column  of  the  cord  to  the  cere- 
brum end  in  the  grey  matter  of  the  thalamus,  as  does  the  central  path 
of  the  afferent  fibres  of  the  opposite  fifth  nerve.  The  posterior  portion 
of  the  thalamus,  or  pulvinar,  forms  part  of  the  central  visual  apparatus; 
for  (fl)  it  is  found  to  be  undeveloped  in  animals  from  which  the  eyeballs 
have  been  removed  soon  after  birth ;  (b)  a  portion  of  the  optic  tract  is 
certainly  connected  with  it;  (c)  in  some  cases  of  atrophy  of  the  occipital 
cortex,  which,  as  we  shall  see,  is  undoubtedly  a  central  area  for  visual 
sensations,  atrophy  of  the  pulvinar  has  also  been  noticed;  {d)  a  lesion 
of  the  pulvinar  may  give  rise  to  hemianopia  (p.  894). 

Hipniorrhage  into  the  caudate  or  lenticular  nucleus  of  the  corpus 
striatum  often  causes  hemiplegia,  but  this  is  frequently  due  to  implica- 
tion of  the  internal  capsule.  It  is  said,  however,  that  lesions  presumably 
confined  to  the  lenticular  nucleus  cause  paralysis  or  paresis  of  the  limbs 
or  face,  which  is  less  severe  than  that  produced  by  lesions  in  the  internal 
capsule.  Experimental  lesions  in  dogs  and  rabbits  are  stated  to  be 
followed  by  disturbances  of  the  heat-regulating  mechanism  and  rise  of 
temperature. 

Certain  structures  belonging  to  the  primary  fore-brain  which  have 
now  lost  some  or  all  of  their  functional  importance  may  nevertheless  be 
mentioned  as  milestones  in  the  march  of  development.  The  pineal 
body  is  made  up  of  the  vestiges  of  the  unpaired  mesial  eye  of  such 
animals  as  the  ancient  labyrinthodonts,  which  resembled  the  eye  of 
invertebrates  in  having  the  retinal  rods  directed  towards  the  cavity 
instead  of  towards  the  circumference  of  the  eyeball.  In  many  living 
forms,  especially  in  certain  lizards,  this  pineal  or  parietal  eye  is  found 
in  a  more  perfect  condition,  though  covered  by  a  thin  membrane.  The 
ganglia  habennlcB,  two  small  collections  of  nerve-cells,  one  of  which  is 
situated  at  the  posterior  part  of  each  thalamus,  are  supposed  by  some 
authorities  to  represent  the  optic  ganglia  of  this  Cyclopean  eye.  They 
are  less  prominent  in  man  than  in  many  of  the  lower  animals.  The 
infundibitlum  is  probably  what  remains  of  the  gullet  of  the  ancestors 
of  the  vertebrates.  The  pituitary  body  is  in  a  different  categor3^  It 
is  now  known  that,  far  from  being  a  useless  vestigial  remnant,  it  has  a 
highly  important  function  (p.  644).  It  consists  of  two  portions,  the 
anterior  lobe,  or  hypophysis,  derived  from  the  buccal  cavity,  the  pos- 
terior lobe,  or  infundibular  body,  from  the  primary  fore-brain. 

Functions  of  the  Cerebellum. — The  elaborate  pattern  of  the  arbor 
vitae,  the  appearance  given  by  the  branched  laminae  in  a  section 
of  the  cerebellum,  excited  the  speculation  of  the  old  anatomists. 
A  structure  so  marvellous  must  be  matched,  they  thought,  with 
functions  as  unique.  At  a  time  when  the  discoveries  of  Galvani 
and  Volta  were  fresh,  and  the  world  ran  mad  on  electricity,  the 
hypothesis  of  Rolando,  that  '  nerve-force  '  was  generated  by  the 
lamellae  of  the  cerebellum  as  electrical  energy  is  generated  by  the 
plates  of  the  voltaic  pile,  ridiculous  as  it  now  appears,  was  not 
unnatural.  The  speculation  of  Gall,  who  connected  the  cerebellum 
with  the  development  of  sexual  emotions  and  the  action  of  the 
generative  mechanisms,  was  based  on  no  fact,  ft  has  been  definitely 
disproved  by  the  observations  of  Luciani,  who  found  that  a  bitch 
deprived  of  its  cerebellum  showed  all  the  phenomena  of  heat  or 


FUNCTIONS  OF  THE  DRAIN 


905 


'  rut,'  was  impregnated,  whelped  at  full  term  in  an  entirely  normal 
manner,  and  manifested  the  maternal  instincts  in  their  full  intensity. 
Flourens  put  forward  the  doctrine  that  the  cerebellum  is  an  organ 
concerned  in  the  co-ordination  of  movements,  and  especially  the 
maintenance  of  equilibrium,  supporting  his  conclusions  by  an 
elaborate  series  of  experiments.  Notwithstanding  the  very  large 
amount  of  experimental  and  clinical  study  which  has  been  devoted 
to  the  cerebellum  since  the  time  of  Flourens,  our  actual  knowledge 


Fig.  363. — Cerebellar  Cortex :  Sectioa  in  Direc- 
tion of  Lamina  (Cajal).  a.  Purkinje's  cell; 
b,  granule  cell  in  inuer  layer;  c,  dendrite  of 
a  granule  cell;  d,  axon  of  a  granule  passing 
into  the  molecular  layer,  where  it  bifur- 
cates into  two  fine  longitudinal  branches 
(Golgi's  method). 


Fig.  364  — Cerei)ellar  Corte.x  : 
Section  across  a  Lamina 
(Cajal).  a,  Purkinje's  cell; 
the  numerous  dots  in  the 
molecular  layer  represent 
cross-sections  of  the  bifur- 
cated axons  of  the  granule 
cells  (Golgi's  method). 


of  its  functions  has  not  greatly  advanced  beyond  the  point  then 
reached.  Some  of  the  more  modern  authorities  restrict  its  influence 
entirely  to  the  actions  on  which  equilibration  depends ;  others  extend 
it  to  all  volitional  movements.  Luciani  looks  upon  it  as  '  an  organ 
which  by  processes  that  do  not  awaken  consciousness  exerts  a  con- 
tinual strengthening  (reinforcing)  action  upon  the  activity  of  all 
other  nerve-centres.'  Sherrington  conceives  of  the  cerebellum  as 
the  head  ganglion  of  the  proprio-ceptive  system — i.e.,  of  the  system 
of  neurons  whose  receptors  lie  not  on  the  surface,  but  in  the  deeper 


9o6  THE  CENTRAL  NERVOUS  SYSTEM 

parts  of  the  body  (labyrinth  of  ear,  muscles,  tendons,  joints,  viscera, 
etc.)  (p.  886).  After  removal  of  the  whole  cerebellum  (in  the  dog 
or  monkey),  there  is  at  first  rigidity  and  tonic  spasm  of  certain 
muscles,  which  contribute  to  the  difficulty  of  co-ordinating  their 
movements.  When  this  stage  has  passed,  the  muscles  all  over  the 
body,  but  especially  those  of  the  loins  and  hind-limbs,  and  those 
which  fix  the  head,  are  weaker  4;han  normal,  are  deficient  in  tone, 
and  contract  with  a  peculiar  want  of  steadiness  (Luciani).  When 
one  lateral  half  of  the  cerebellum  is  removed,  the  symptoms  affect 
especially  the  muscles  on  the  same  side.  In  extensive  lesions  of 
the  cerebellum  in  man  what  has  been  noticed  is  a  marked  inability 
to  m^ntain  the  upright  posture,  giddiness,  a  staggering  gait, 
twitching  movements  of  the  eyes  (nystagmus),  tremor  accompany- 
ing voluntary  movements — in  a  word,  a  general  breakdown  of  the 
co-ordinating  machinery,  and  especially  of  the  part  of  it  concerned 
in  the  movements  necessary  for  locomotion,  and  for  the  maintenance 
of  the  equilibrium  of  the  body — the  so-called  cerebellar  ataxia. 
There  is  no  sensory  paralysis  and  none  of  voluntary  movement 
such  as  lesions  of  the  cerebral  cortex  produce,  nor  is  there  any 
psychical  disturbance.  In  cases  of  congenital  defect  of  the  cere- 
bellum, the  power  of  walking,  and  even  of  standing,  may  be  late  in 
being  acquired,  and  imperfect.  But  it  is  remarkable  what  great 
deficiencies  in  the  cerebellar  substance  are  often  compensated  for 
when  estabhshed  early  in  life,  so  that  even  cases  of  marked  atrophy 
or  lack  of  development  have  sometimes  been  recognised  for  the 
first  time  at  the  necropsy. 

The  connections  of  the  cerebellum  with  other  parts  of  the  central 
nervous  system  and  with  the  periphery  corroborate  the  direct 
results  of  experiment.  For,  in  addition  to  the  visual  impressions, 
the  most  important  afferent  impulses  concerned  in  equilibration  are 
those  from  the  semicircular  canals  and  vestibule  of  the  internal  ear, 
the  muscles,  tendons,  joints,  etc.,  and  certain  portions  of  the  skin, 
such  as  that  of  the  soles  of  the  feet.  And  the  cerebellum,  as  we  have 
seen  (p.  857),  is  linked  with  all  of  these,  and  has  besides  an  extensive 
crossed  connection  through  the  middle  and  superior  peduncles  with 
the  opposite  cerebral  hemisphere.  The  importance  and  extent  of 
this  crossed  connection  with  the  great  brain  is  illustrated  by  the  facts 
that  in  disease  atrophy  or  deficient  development  of  one  cerebellar 
hemisphere  is  associated  with  a  similar  condition  of  the  opposite 
cerebral  hemisphere,  and  that  a  lesion  in  one-half  of  the  cerebellum 
affects  chiefly  the  co-ordination  of  the  movements  of  the  same  side 
of  the  body — that  is  to  say,  of  the  side  connected  with  the  opposite 
cerebral  hemisphere. 

We  do  not  as  yet  know  the  full  significance  of  this  extraordinarily 
free  communication  of  the  grey  matter  of  the  cerebellum  with  every 
part  of  the  central  nervous  system.     But  it  is  evident  that  by  the  broad 


FUNCTIONS  OF  THE  BRAIN 


907 


highway  of  the  restiform  body,  or  the  cross-country  routes  from  cere- 
bral cortex  to  cerebelhim,  impulses  may  reach  it  from  every  quarter; 
while  impulses  passing  out  from  it  along  its  peduncles  may  influence 
the  motor  discharge  either  indirectly  through  the  Rolandic  cortex  and 
the  pyramidal  tract,  or  more  directly  through  the  antero-lateral  de- 
scending spinal  path  that  brings  it  into  relation  with  the  nuclei  of 
origin  of  the  motor  nerves.  It  is  an  organ  so  connected  that  is  suited 
to  take  cognizance  of  the  multitudes  of  afferent  impressions  concerned 
in  the  co-ordination  of  movements  and  the  maintenance  of  equilibrium, 
and  to  regulate  the  outflow  of  efferent  impulses  in  correspondence  with 
the  inflow  of  afferent. 

Sherrington  points  out  that  all  the  modem  theories  of  cerebellar 
function  harmonize  with  his  conception  of  the  cerebellum  as  the  head 
ganglion  of  the  proprio-ceptive  system  (p.  905).  The  most  influential 
of  the  proprio-ceptive  organs  being  the  labyrinth,  the  central  organ  of 
the  whole  proprio-ceptive  mechanism  is  built  up  over  the  central  con- 
nections of  the  labyrinth.  Thither  converge  connecting  (internuncial) 
paths  from  the  central  endings  of  proprio-ceptive  neurons  in  all  seg- 
ments of  the  body  (from  joints,  muscles,  tendons,  ligaments,  viscera, 
etc.).  Thus  a  central  organ  is  developed,  which  varies  in  size  and 
complexity  in 
different  kinds  of 
animals  accord- 
ing to  the  com- 
plexity of  their 
habitual  move- 
ments. 

Afferent  Im- 
pulses concerned 
in  Equilibration 
and  Orientation. 
^This  is  a  con- 
venient place  to 
consider  a  little 
more  in  detail 
the   nature  and 

peripheral  sources  of  some  of  the  most  important  afferent  impressions 
concerned  in  equilibration  and  orientation. 

(i)  Afferent  Impulses  from  the  Semicircular  Canals. — The  semi- 
circular canals  are  three  in  number,  and  lie  nearly  in  three  mutually 
rectangular  planes:  the  external  canal  in  the  horizontal  plane,  the 
superior  canal  in  a  vertical  longitudinal  plane,  and  the  posterior  canal 
in  a  vertical  transverse  plane.  Each  canal  bulges  out  at  one  end  into 
a  swelling,  or  ampulla,  which  opens  into  the  utricular  division  of  the 
vestibule  (Figs.  365,  436).  The  other  extremities  of  the  superior  and 
posterior  canals  join  together,  and  have  a  common  aperture  into  the 
utricle,  but  the  undilated  end  of  the  external  or  horizontal  canal  opens 
separately.  The  utricle  and  the  semicircular  canals  are  thus  connected 
by  five  distinct  orifices.  The  greater  part  of  the  internal  surface  of 
the  membranous  canals,  utricle  and  saccule,  is  lined  by  a  single  layer 
of  flattened  epithelium.  But  at  or.e  part  of  each  ampulla  projects  a 
transverse  ridge,  the  crista  acustica.  covered  not  with  squamous,  but 
with  long  columnar  epithelium.      Hair-like  processes  (auditory  hairs) 


Fig-  365- — The  Semicircular  Canals  (Diagrammatic)  (after 
Ewald).  H,  horizontal  or  external;  S,  superior:  P,  pos- 
terior. The  two  horizontal  canals  lie  in  the  same  plane. 
The  plane  of  the  superior  vertical  canal  of  one  side  is 
parallel  to  the  plane  of  the  posterior  vertical  canal  of  the 
opposite  side. 


9o8  THE  CENTRAL  NERVOUS  SYSTEM 

are  borne  by  some  of  the  columnar  cells,  between  which  lie  more 
elongated  fibre-like  supporting  cells.  The  hairs  project  into  a  mucus- 
like mass,  sometimes  containing  otoconia,  or  crj^stals  of  calcium  car- 
bonate. The  ampullae,  like  the  rest  of  the  membranous  labyrinth,  is 
filled  with  a  watery  fluid  called  endolymph.  The  utricle  and  saccule 
have  each  a  somewhat  similar  but  broader  elevation,  the  macula 
acustica,  covered  with  epithelium  and  hair-cells  of  the  same  character, 
and  the  hairs  project  into  a  similar  mass  in  which  otoconia  are  con- 
stantly present.  In  some  animals,  as  fishes,  the  calcareous  matter  in 
the  utricle  and  saccule  forms  masses  of  considerable  size  {otoliths). 
Fibres  of  the  auditory  nerve  end  in  arborizations  around  the  bodies 
of  the  hair-cells  of  the  maculae  and  cristse  acusticae.  We  have  already 
seen  that  it  is  the  ventral  or  vestibular  division  of  the  nerve  which  is 
especially  related  to  the  vestibule  (p. 


There  is  very  strong  evidence  that  the  semicircular  canals  are  con- 
cerned, not  in  hearing,  but  in  equilibration.  A  pigeon  from  which 
the  membranous  canals  have  been  removed  still  hears  perfectly 
well  so  long  as  the  cochlea  is  intact,  but  exhibits  the  most  profound 
disturbance  of  equihbrium.  If  the  horizontal  canal  is  destroyed 
or  divided,  the  pigeon  moves  its  head  continually  from  side  to  side 
around  a  vertical  axis;  if  the  superior  canal  is  divided,  the  head 
moves  up  and  down  around  a  horizontal  axis.  The  power  of  co- 
ordination of  movements  is  diminished,  but  not  to  the  same  extent 
in  all  kinds  of  animals.  Thrown  into  the  air,  the  pigeon  is  helpless; 
it  cannot  fly;  but  a  gdbse  with  divided  semicircular  canals  can  still 
swim.  The  condition  is  only  temporary,  even  when  the  injury 
involves  the  three  canals  on  one  side ;  but  if  the  canals  on  both  sides 
are  destroyed,  recovery  is  tardy,  and  often  incomplete.  In  mam- 
mals the  loss  of  co-ordination  is  much  less  than  in  birds;  and  move- 
ments of  the  eyes,  the  direction  of  which  depends  on  the  canal 
destroyed,  take  to  a  large  extent  the  place  of  movements  of  the 
head.  The  effects  of  destructive  lesions  have  their  counterpart  in 
the  phenomena  caused  by  stimulation;  excitation  of  a  posterior 
canal,  for  example,  in  the  pigeon  causes  movements  of  the  head 
from  side  to  side. 

Lee's  results  in  fishes  are,  on  the  whole,  of  similar  tenor.  Mechan- 
ical stimulation  of  the  ampullae  in  the  dogfish,  by  pressing  on  them 
with  a  blunt  needle,  calls  forth  characteristic  movements  of  the 
eyes  and  fins,  and  electrical  stimulation  of  the  auditory  nerve 
causes  movements  compounded  of  the  separate  movements  obtained 
by  stimulation  of  the  ampullae  one  by  one.  Lee  concludes  that  the 
semicircular  canals  are  the  sense-organs  for  dynamical  equihbrium 
{i.e.,  equilibrium  of  an  animal  in  motion),  and  the  utricle  and  saccule 
for  statical  equilibrium  {i.e.,  equilibrium  of  an  animal  at  rest). 

The  evidence  from  all  sources  points  strongly  to  the  conclusion 
that  afferent  impulses  are  actually  set  up  in  the  fibres  of  the  auditory 
nerve,  through  the  hair-cells,  by  alterations  of  pressure  or  by  stream- 
ing movements  of  the  endolymph  when  the  position  of  the  head  is 


FUNCTIONS  OF  THE  BRAIN  909 

changed.  Rotation  of  the  head  to  the  right  may  be  supposed  to 
cause  the  endolymph  in  the  right  external  canal,  in  virtue  of  its 
inertia,  to  lag  behind  the  movement,  and  to  press  upon  the  anterior 
surface  of  the  ampulla.  The  disorders  of  movement  after  lesions  of 
the  canals  may  be  explained  as  the  result  of  the  withdrawal  of 
certain  of  these  afferent  impulses,  and  the  consequent  overthrow  of 
that  equipoise  of  excitation  necessary  for  the  maintenance  of  equi- 
librium. An  experiment  of  Kreidl  on  a  crustacean  (palaemon)  has 
made  it  probable  that  the  otoliths  by  their  weight  may  mechani- 
cally affect  the  hair-cells,  and  so  increase  their  sensitiveness  to 
changes  of  position.  This  animal  has  the  peculiarity  that  in  moult- 
ing the  inner  lining  of  the  otocysts,  in  which  the  otoliths  lie  and 
which  open  to  the  exterior,  are  shed  along  with  the  otoliths.  When 
moulting  is  over,  the  animal  by  means  of  its  claws  conveys  fine 
sand  grains  into  the  otocysts,  where  they  function  as  otoliths. 
Kreidl  placed  the  animal  after  moulting  upon  finely  powdered  iron, 
some  of  which  was  conveyed  into  the  otocyst  instead  of  sand.  It 
was  now  found  possible  to  obtain  definite  reactions  from  the  animal 
in  the  presence  of  a  magnet,  which,  of  course,  tended  to  attract  the 
ferruginous  otoliths,  and  so  to  alter  their  position  with  reference 
to  the  hairs.  The  way  in  which  the  animal  changed  its  position  in 
response  to  the  magnet  could  be  satisfactorily  accounted  for  on  the 
hypothesis  that  normally  the  contact  of  the  otoliths  \\ath  the  hairs 
is  altered  under  the  influence  of  gravity  when  such  changes  of  posi- 
tion occur.  Even  in  man  there  is  evidence  of  the  existence  of  some 
mechanism  not  depending  on  the  muscular  sense  or  on  impressions 
passing  up  the  channels  of  ordinary  or  special  sensation,  by  which 
orientation  (the  determination  of  the  position  of  the  body  in  space) 
is  rendered  possible.  For  a  man  lying  perfectly  still,  with  eyes  shut, 
on  a  horizontal  table  which  is  made  to  rotate  uniformly,  can  not 
only  judge  whether,  but  also  in  what  direction,  and  approximately 
through  what  angle,  he  is  moved.  The  phenomena  of  pathology 
afford  weighty  additional  testimony  in  favour  of  the  equilibratory 
function  of  the  semicircular  canals.  For  many  cases  of  vertigo  are 
associated  with  changes  in  the  internal  ear  (Meniere's  disease). 
And  while  nearly  every  normal  individual  becomes  dizzy  when 
rapidly  rotated,  35  per  cent,  of  deaf-mutes  are  entirely  unaffected 
(James),  and  the  proportion  seems  to  be  much  higher  among  con- 
genital deaf-mutes.  Kreidl  and  Bruck,  too,  have  found  that  ab- 
normalities of  locomotion  and  equilibration  are  much  more  common 
in  deaf-and-dumb  children  than  in  others.  Now,  in  these  cases 
the  defect  is  usually  in  the  internal  ear.  We  must  conclude,  then, 
that  the  co-ordination  of  muscular  movements  necessary  for  equili- 
brium is  achieved  in  some  centre,  to  which  afferent  impulses  pass 
from  the  internal  ear  by  the  vestibular  branch  of  the  auditory-  nerve, 
and  from  which  efferent  impulses  pass  out  to  the  muscles.     If,  as 


9IO  THE  CENTRAL  NERVOUS  SYSTEM 

there  is  strong  reason  to  believe,  this  centre  is  situated  in  the  cere- 
bellum, the  efferent  path  is,  as  already  suggested  (p.  906),  partly  an 
indirect  one  (perhaps  by  commissural  fibres  to  the  Rolandic  area, 
and  then  out  along  the  pjTamidal  tract),  or  more  probably  to  lower 
centres,  perhaps  in  the  posterior  portion  of  the  optic  thalamus, 
which  control  such  massive  co-ordinated  movements  as  those  con- 
cerned in  walking  and  the  maintenance  of  the  normal  attitude,  and 
thence  out  along  certain  tracts  that  connect  the  thalamus  to  the 
spinal  cord  (p.  858). 

Ewald  has  made  an  observation  which  illustrates  the  peculiar 
relation  of  the  semicircular  canals  to  the  muscular  system — namely, 
that  the  labyrinth  (in  rabbits)  influences  the  course  of  rigor  mortis 
in  the  striped  muscles.  Rigor  does  not  come  on  so  soon  on  the  side 
from  which  the  labyrinth  has  been  removed.  He  attributes  to  the 
labyrinth,  as  one  of  its  functions,  the  maintenance  of  a  certain 
tonus  in  the  entire  skeletal  musculature. 

(2)  Afferent  Impressions  from  the  Muscles. — Muscles  are  richly 
supplied  with  afferent  fibres,  for  about  half  of  the  fibres  in  the  nerves 
of  skeletal  muscles  degenerate  after  section  of  the  posterior  roots 
beyond  the  ganglia  (Sherrington).  Various  kinds  of  impressions 
may  pass  up  these  nerves:  [a)  Impressions  giving  rise  to  pain,  as  in 
muscular  cramp  and  in  experimental  excitation  of  even  the  finest 
muscular  nerve-filament ;  (b)  impulses  causing  a  rise  of  blood-pres- 
sure; (c)  impulses  which  are  not  associated  with  a  distinct  impres- 
sion in  consciousness,  but  which  enable  us  to  localize  the  position 
of  the  limbs,  head,  eyes,  and  other  parts  of  the  body;  {d)  impulses 
which  inform  us  as  to  the  extent  and  force  of  muscular  contraction, 
and  seem  to  underlie  the  so-called  muscular  sense.  It  is  the  last 
two  kinds — if,  indeed,  they  are  distinct — which  must  be  concerned 
in  equilibration.  In  locomotor  ataxia  such  impressions  are  blocked 
by  degeneration  in  a  part  of  the  afferent  path  (p.  887),  and  disorders 
of  equilibrium  are  the  result. 

(3)  Afferent  Impressions  from  the  Skin. — Of  the  various  kinds  of 
impulses  that  arise  in  the  nerve-endings  of  the  skin,  only  thote  of 
touch  and  pressure  seem  to  be  concerned  in  the  maintenance  of 
equilibrium.  When  the  soles  of  the  feet  are  rendered  insensitive  by 
local  anaesthesia  or  by  cold,  and  the  person  is  directed  to  close  his 
eyes,  he  staggers  and  sways  from  side  to  side.  The  disturbance  of 
equilibrium  in  locomotor  ataxia  must  be  partly  attributed  to  the 
loss  of  these  tactile  sensations,  for  numbness  of  the  feet  is  a  frequent 
symptom,  and  the  patient  asserts  that  he  does  not  feel  the  ground. 
An  interesting  illustration  of  the  importance  of  afferent  impulses 
from  the  skin  in  the  maintenance  of  equilibrium  is  afforded  by  the 
behaviour  of  a  frog  deprived  of  its  cerebral  hemispheres.  Such  a 
frog  will  balance  itself  on  the  edge  of  a  board  like  a  normal  animal 
but  if  the  skin  be  removed  from  the  hind-legs,  it  will  fall  like  a  log! 


FUNCTIONS  OF  THE  BRAIN 


gii 


In  birds  and  lower  vertebrates  the  cerebellum  is  only  represented 
by  the  w.irni.  Yet  in  many  of  these  animals  the  same  characteristic 
disturbances  follow  its  removal  as  in  the  higher  animals  where  the 
cerebellar  hemispheres  have  become  so  prominent.  Indeed,  it  was 
m  .inly  on  the  pigeon  that  Flourens  made  his  classical  experiments. 
At  first  the  pigeon  can  neither  fly  nor  feed  itself.  When  it  attempts 
to  walk,  extensor  spasms  of  the  legs  come  on,  and  it  falls,  wildly 
struggling  and  apparently  panic-stricken,  to  the  ground.  The  power 
of  flight  is  soon  regained'  but  for  a  long  time  the  animal  is  unable  to 
perch,  the  legs  and  talons  stiffening  in  rigid  extension  as  it  attempts 
to  alight. 

In  the  higher  animals  stimulation  of  certain  parts  of  the  worm  and 
lateral  lobe  causes  conjugate  movements  of  che  eyes  towards  the  same 
side,  both  eyes  being  turned  to  the  right — e.g..  when  the  cerebellum  is 
stimulated  to  the  right  of  the  middle  line.  Inhibition  of  movement 
can  also  be  elicited  from  the  organ.  Excitation  of  the  cerebellar  cortex 
for  some  distance 
outwards  from  the  y^"*  '*V 

line  of  junction  of  ,-- -^^     /     i-«-      \        ^-^      L» 

the  superior  worm  '''^'^■ 

with  the  lateral  lobe 
in  animals  which 
exhibit  tonic  con- 
traction jf  extensor 
muscles  after  ex- 
cision of  the  cere- 
bral hemispheres 
(decerebrate  rigid- 
ity or  acerebral 
tonus,  ao  it  is  called) 
causes  immediate 
relaxation  of  the 
rigid  muscles  of  the 
neck,  tail,  and 
especially  the  an- 
terior limb,  particu- 
larly on  the  same 
side.  The  relaxation 
of  the  extensors 
may  be  accom- 
panied by  contrac- 
tion of  the  antago- 
nistic flexors — for  example,  relaxation  of  the  triceps  and  contraction  of 
the  biceps  (Horsley  and  Lowenthal).  But  this  can  scarcely  be  considered 
a  reaction  specific  to  the  cerebellum.  For  Sherrington,  who  finds  that 
the  tonus  or  spasm  is  largely  due  to  centripetal  impulses  coming  from 
the  rigid  limb,  has  been  able  to  inhibit  it  by  stimulation  of  various 
other  regions,  including  the  portion  of  the  cerebral  cortex  in  front  of 
the  fi.ssure  of  Rolando  (p.  921). 

Localization  of  Function  in  the  Cerebellum. — The  confusion  which  so 
long  reigned  in  regard  to  this  matter  li.is  in  great  measure  been  cleared 
up  by  recent  physiological  work^ollowing  on  a  more  accurate  anatomical 
mapping  of  the  lobes  and  lobules  of  the  cerebellum  in  accordance  with 
their  genetic  relations  (Bolk)  (Fig.  366]. 

Following  this  scheme,  van  Rynoerk  lias  obtained  satisfactory 
evidence  of  localization  of  function.  Thus  the  lobulus  simplex  con- 
stitutes a  centre  for  the  neck  muscles,  and  the  elimination  of  its  influ- 


Fig.  366. — Scheme  of  Dog's  Cerebellum  (Dorsal  View),  ac- 
cording to  the  Anatomical  Division  of  Bolk  (after  van 
Rynberk).  La,  lobus  anterior,  which  is  separated  from 
the  larger  posterior  lobe  by  the  deep  primary  fissure 
(sulcus  primarius),  Spr;  Ls,  lobulus  simplex;  Si,  sulcus 
intercruralis;  C^,  crus  primum;  C^,  crus  secundum; 
L.ans,  lobulus  ansiformis;  Lp,  lobulus  paramedianus; 
Lmp,  lobulus  medianus  posterior;  Fv.  formatio  vermi- 
cularis  (pars  tonsillaris);  Sp,  sulcus  paramedianus. 


912  THE  CENTRAL  NERVOUS  SYSTEM 

ence  by  excision  leads  to  movements  of  the  head  (so-called  head 
nystagmus).  The  anterior  extremity  is  represented  by  a  centre  in  the 
crus  primum.  and  the  posterior  extremity  by  a  centre  in  the  cms 
secundum,  of  the  ansiform  lobule  of  its  own  side,  and  injury  in  the 
region  of  these  centres  is  associated  with  abnormal  movements  of  the 
corresponding  fore  and  hind  foot  respectively.  Extirpation  of  a  lobulus 
paramedianus  causes  rolling  movements  of  the  body  around  its  long 
axis  or  bending  of  the  body  to  one  side,  and  this  centre  is  connected 
with  the  muscles  of  the  trunk.  It  is  still  an  open  question  whether  in 
the  function  of  these  centres  only  the  cortex  of  the  lobules  is  concerned, 
or  in  addition  the  corresponding  portions  of  the  central  nuclei  of  the 
cerebellum.  These  observations  are  supported  by  other  facts.  For 
example,  microscopical  studies  have  shown  that  definite  regions  of  the 
cerebellar  cortex  are  especially  connected  with  definite  levels  of  the 
spinal  cord.  Further,  the  lobulation  of  the  cerebeUum  in  mammals 
keeps  pece  with  the  increase  in  complexity  of  the  voluntary  motor 
apparatus  of  the  whole  body,  and  the  variations  in  the  degree  of 
development  of  d(  finite  lobules  are  related  to  the  variatiorai  in  the 
anatomical  and  physiological  development  of  the  corresponding  groups 
of  muscles.  All  this  fits  in  well  with  the  idea  that  the  cerebellum  is  a 
great  reflex  mechanism  standing  in  intimate  relation  on  the  one  hand 
to  numerous  afferent  paths  (skin,  muscles,  labyrinth,  etc.),  and  on  the 
other  to  the  voluntary-  muscles.  It  is  the  precise  nature  of  the  influ- 
ence exerted  by  it  upon  the  latter  which  is  in  doubt,  whether  an  aug- 
menting sthenic  influence,  as  Luciani  supposes,  or  a  co-ordinating  in- 
fluence, as  Flourens  assumed,  or  a  combination  of  these. 

Forced  Movements. — We  have  incidentally  mentioned  that  in  fishes 
injuries  to  the  semicircular  canals  may  give  rise  to  movements  which 
seem  to  be  beyond  the  control  of  the  animal,  and  which  have  conse- 
quently received  the  name  of  '  forced  movements.'  It  may  be  added 
that  when  the  internal  ear  of  a  Necturus  (one  of  the  tailed  amphibia) 
is  destroyed  on  one  side,  rapid  movements  of  rotation  around  a  longi- 
tudinal axis  are  observed.  The  animal  spins  round  and  round  ap- 
parently without  voluntary  control,  purpose,  or  fatigue.  The  direction 
of  rotation  is  towards  the  side  of  the  lesion,  the  observer  being  sup- 
posed to  look  down  upon  the  animal  as  it  lies  in  its  normal  position. 
After  a  time  it  becomes  quiescent;  but  the  forced  movements  can  be 
again  produced  by  pinching  or  exciting  it  in  other  ways.  In  man,  too, 
during  the  passage  of  a  galvanic  current  through  the  head  by  electrodes 
applied  just. behind  the  ears,  a  tendency  to  move  the  head  towards  the 
anode  is  experienced.  The  person  may  resist  the  tendency,  but  if  the 
current  be  strong  enough  his  resistance  will  be  overcome;  he  will  exe- 
cute a  forced  movement.  When  the  head  turns  towards  the  anode 
the  eyes  move  in  the  same  direction,  and  then  undergo  jerking  move- 
ments towards  the  kathode.  There  is  at  the  same  time  a  feeling  of 
vertigo.  Complex  as  such  an  experiment  is,  involving  as  it  does  stimu- 
lation of  so  many  structures  within  the  cranium,  there  is  reason  to 
believe  that  it  is  the  excitation  of  the  semicircular  canals,  or  their 
cerebellar  connections,  that  is  responsible  for  these  forced  movements. 
For  when  the  experiment  is  performed  on  a  pigeon,  forced  movements 
are  caused  so  long  as  the  membranous  canals  are  intact,  but  not  after 
they  have  been  destroyed  (Ewald).  The  observation  of  Rawitz,  that 
the  peculiar  rotatory  movements  of  the  so-called  Japanese  dancing 
mice  are  associated  with  marked  anatomical  peculiarities  in  the  laby- 
rinth, is  another  fact  in  favour  of  the  connection  of  the  canals  with 
the  maintenance  of  equilibrium  and  the  sense  of  rotation.  So  is  the 
relation  between  the  degree  of  development  of  the  canals  in  different 


FUNCTIONS  OF  THE   BRA IX  913 

species  of  birds  and  the  degree  of  agility  in  the  co-ordination  of  their 
movements  (Laiidenbach). 

But  forced  movements  may  also  follow  injuries  (especially  unilateral) 
to  many  portions  of  the  brain — e.g.,  the  pons,  crus  cerebri,  posterior 
corpora  quadrigemina.  corpus  striatum,  even  the  cerebral  cortex,  and 
above  all  the  cerebellum.  The  movements  arc  of  the  most  various 
kinds.  The  animal  may  run  round  and  round  in  a  circle  (circus  move- 
ment);  or,  with  the  tip  of  its  tail  as  centre  and  the  length  of  its  body 
as  radius,  it  may  describe  a  circle  with  its  head,  as  the  iiand  of  a  clock 
does  (clock-hand  movement);  or  it  may  rush  forward,  turning  end- 
less somersaults  as  it  goes.  Intervals  of  rest  alternate  with  paroxysms 
of  excitement,  and  the  latter  may  be  brought  on  by  stimulation.  In 
man  forced  movements  associated  with  vertigo  have  been  sometimes 
seen  in  cases  of  tumour  of  th6  cerebellum — e.g.,  involuntary  rotation 
of  the  body  in  tumour  of  the  middle  peduncle.  No  entirely  satisfac- 
tory explanation  of  these  forced  movements  has  been  given.  They  are 
evidently  connected  with  disturbance  of  the  mechanism  of  co-ordina- 
tion, leading  to  a  loss  of  proportion  in  the  amount  o^  the  motor  dis- 
charge to  muscles  or  groups  of  muscles  accustomed  to  act  together  in 
executing  definite  movements.  For  instance,  in  circus  movements  the 
muscles  of  the  outer  side  of  the  body  contract  more  powerfully  than 
those  of  the  inner  side,  and  the  animal  is  therefore  constrained  to  trace 
a  circle  instead  of  a  straight  line,  the  excess  of  contraction  on  the  outer 
side  being  analogous  to  the  acceleration  along  the  radius  in  the  case 
of  a  point  moving  in  a  circle. 

In  connection  with  the  consideration  of  the  mechanism  of  equilibra- 
tion, a  short  account  of  the  muscular  actions  concerned  in  the  main- 
tenance of  the  erect  posture  so  characteristic  of  man,  and  of  those 
concerned  in  locomotion,  is  subjoined  here: 

Standing. — In  the  upright  posture  the  body  is  supported  chiefly  by 
non-muscular  structures,  the  bones  and  ligaments.  But  muscles  also 
play  an  essential  part,  for  it  is  only  peculiarly-gifted  individuals,  like 
some  of  the  fishermen  of  the  North  Sea,  who  can  go  to  sleep  on  their 
feet,  and  a  dead  body  cannot  be  made  to  stand  erect.  The  condition 
of  equilibrium  is  that  the  perpendicular  dropped  from  the  centre  of 
gravity  to  the  ground  should  fall  within  the  base  of  support — that  is, 
within  the  area  enclosed  by  the  outer  borders  of  the  feet  and  lines 
joining  the  toes  and  heels  respectively.  The  centre  of  gravity  alters 
its  position  with  the  position  of  the  body,  which  tends  to  fall  whenever 
the  perpendicular  cuts  the  ground  beyond  the  base  of  support. 

In  the  comfortable  and  natural  erect  position  the  centre  of  gravity 
of  the  head  is  a  little  in  front  of  the  vertical  plane  passing  through  the 
occipital  cond^des,  and  as  much  as  4  centimetres  in  front  of  the  vertical 
plane  passing  through  the  ankle-joints.  A  certain  degree  of  contrac- 
tion of  the  muscles  of  the  nape  of  the  neck  is  required  to  balance  it. 
When  these  muscles  are  relaxed,  as  in  sleep,  the  head  must  fall  forward, 
and  this  is  the  reason  why  Homer  or  any  lesser  individual  nods.  In 
animals  which  go  upon  all-fours  none  of  the  weight  of  the  head  bears 
directly  upon  the  occipito-atloid  articulation;  its  support  by  muscular 
action  alone  would  be  an  intolerable  fatigue,  and  the  ligamentum 
nucha?  is  specially  strengthened  to  hold  it  up. 

The  vertebral  column  is  kejjt  erect  by  the  ligaments  and  muscles 
of  the  back.  The  centre  of  gravity  of  the  trunk  lies  almost  vertically 
over  the  horir.ontal  line  joining  the  two  acetabula,  but  the  centre  of 
gravity  of  the  whole  body  is  aboMt  the  level  of  the  third  sacral  vertebra, 
and  a  little  more  than  4  centimetres  in  front  of  the  vertical  plane 
passing  through  the  ankle-joints.     Equilibrium  1:   ni;:intained  by  con- 

5S 


914  THE  CENTRAL  NERVOUS  SYSTEM 

traction  of  the  muscles  of  the  back  and  of  the  legs.  By  means  of  the 
.muscular  sense,  and  the  tactile  sensations  set  up  by  the  pressure  of  the 
soles  on  the  ground,  alterations  in  the  position  of  the  centre  of  gravity, 
and  consequent  deviations  of  the  perpendicular  passing  through  it, 
are  detected,  and  adjustment  of  the  amount  of  contraction  of  this  or 
the  other  muscular  group  is  promptly  made. 

In  standing  at  '  attention  '  the  heels  are  close  together,  the  legs  and 
back  straightened  to  the  utmost,  and  the  head  erect;  the  weight  falls 
equally  upon  both  legs,  but  the  advantage  may  be  more  than  counter- 
balanced by  the  muscular  exertion  associated  with  this  more  orna- 
mental than  useful  position.  In  '  standing  at  ease,'  practically  the 
whole  weight  is  supported  by  one  leg,  the  perpendicular  from  the 
centre  of  gravity  passing  through  the  knee  and  ankle-joint.  The 
centre  of  gravity  is  brought  over  the  supporting  leg  by  flexure  of  the 
body  to  the  corresponding  side,  and  comparatively  little  muscular 
effort  is  required.  The  other  foot  rests  lightly  on  the  ground,  the 
weight  of  the  leg  itself  being  almost  balanced  by  the  atmospheric 
pressure  acting  upon  the  air-tight  and  air-free  cavity  of  the  hip-joint. 
The  light  touch  of  this  foot  varies  slightly  from  time  to  time,  so  as  to 
maintain  equilibrium. 

When  the  head  or  arms  are  moved,  or  the  body  swayed,  the  centre 
of  gravity  is  correspondingly  displaced,  and  it  is  by  such  movements 
that  tight-rope  dancers  continue  to  keep  the  perpendicular  passing 
through  it  always  within  the  narrow  base  of  support. 

In  sitting,  the  base  of  support  is  larger  than  in  standing,  and  the 
equilibrium  therefore  more  stable.  The  easiest  posture  in  sitting 
without  support  to  the  back  or  feet  is  that  in  which  the  perpendicular 
from  the  centre  of  gravity  passes  through  the  horizontal  line  joining 
the  two  tubera  ischii. 

Locomotion. — In  walking,  the  legs  are  alternately  swung  forward 
and  rested  on  the  ground.  With  most  persons  the  swinging  foot  first 
strikes  the  ground  by  the  heel;  then  the  sole  comes  down,  the  heel 
rises,  the  leg  is  extended,  and,  with  a  parting  push  from  the  toe,  the 
leg  again  swings  free.  By  this  manoeuvre  the  body  is  raised  vertically, 
tilted  to  the  opposite  side,  and  also  pushed  in  advance. 

The  forward  swing  of  the  leg  is  only  slightly,  if  at  all,  due  to  mus- 
cular action;  it  is  more  like  the  oscillation  of  a  pendulum  displaced 
behind  its  position  of  equilibrium,  and  swinging  through  that  position, 
and  in  front  ot  it,  under  the  influence  of  gravity.  For  this  reason  the 
natural  pace  of  a  tall  man  is  longer  and  slower  than  that  of  a  short 
man;  but  it  may  be  modified  by  voluntary  effort,  as  when  a  rank  of 
soldiers  of  different  height  keeps  step.  The  lateral  swing  of  the  body 
is  illustrated  by  the  everyday  experience  that  two  persons  knock 
against  each  other  when  they  try  to  walk  close  together  without 
keeping  step.  In  step  both  swing  their  bodies  to  the  same  side  at 
the  same  moment,  and  there  is  no  jarring.  Even  in  the  fastest  walk- 
ing on  level  ground  there  is  a  short  time  during  which  both  feet  touch 
the  ground  together,  the  one  leg  not  beginning  its  swing  until  the 
other  foot  has  begun  to  be  set  down.  In  running,  on  the  other  hand, 
there  is  an  interval  during  which  the  body  is  completely  in  the  air, 
while  in  walking  uphill  or  in  carrying  a  load  the  one  foot  is  not  raised 
until  the  other  has  been  firmly  planted. 

Functions  of  the  Cerebral  Cortex. — When  an  animal,  hke  a  frog, 
is  deprived  of  its  cerebral  hemispheres,  the  power  of  automatic 
voluntary  movement  appears  to  be  definitively  and  entirely  lost. 


FUNCTIONS  OF  THE  IJHAIN  y^i 

The  animal,  as  soon  as  the  effects  of  the  ana;sthetic  and  the  shock 
of  the  operation  have  passed  away,  draws  up  its  legs,  erects  its  head, 
and  assumes  the  characteristic  position  of  the  normal  frog  at  rest. 
So  close  maybe  the  resemblance,  that  if  all  external  signs  of  the  opera- 
tion have  been  concealed,  it  may  not  be  possible  for  a  casual  ob- 
server to  tell  merely  by  inspection  which  is  the  intact  and  which  the 
'  brainless  *  frog.  The  latter  will  jump  if  it  be  touched  or  otherwise 
stimulated.  It  will  croak  if  its  Hanks  be  stroked  or  gently  squeezed 
together.  It  will  swim  if  thrown  into  water.  If  placed  on  its  back, 
it  will  promptly  recover  its  normal  position.  But  it  will  do  all 
these  things  as  a  machine  would  do  them,  without  purpose,  without 
regard  to  its  environment,  with  a  kind  of  '  fatal  '  regularity. 
Every  time  it  is  stimulated  it  will  jump,  ever}/  time  its  flanks  are 
squeezed  it  wilt  croak,  and,  in  the  absence  of  all  stimulation,  it  will 
sit  still  till  it  withers  to  a  mummy,  even  by  the  side  of  the  water 
that  might  for  a  while  preserve  it. 

A  Necturus,  without  its  cerebral  hemispheres,  will,  like  the  frog, 
refuse  to  lie  on  its  back.  On  stimulation  it  moves  its  feet  or  tail, 
or  its  whole  body;  but  if  not  interfered  with,  it  lies  for  an  indelinite 
time  in  the  same  position.  Its  gills  are  seen  to  execute  rlu'thmic 
movements,  which  never  stop,  and  rarely  slacken,  except  for  an 
instant,  when  some  part  of  the  skin,  particularly  in  the  region  of 
the  head,  is  mechanically  or  electrically  stimulated.  The  normal 
Necturus,  on  the  other  hand,  lies  for  long  periods  with  its  gills  at 
perfect  rest,  and  when  stimulated,  moves  for  a  considerable  distance. 
After  a  time — two  months  or  more — it  is  true  the  brainless  frog, 
if  it  be  kept  alive,  as  may  be  done  by  careful  attention,  will  recover 
a  certain  portion  of  the  powers  which  it  has  lost  by  removal  of  the 
cerebral  hemispheres ;  and,  indeed,  the  longer  it  lives,  the  nearer  it 
approximates  to  the  condition  of  a  normal  frog.  A  brainless  frog 
has  been  seen  to  catch  flies  and  to  bury  itself  as  winter  drew  on. 
A  fish  even  three  days  after  the  destruction  of  its  cerebrum  has  been 
seen  to  dart  upon  a  worm,  seize  it  before  it  had  time  to  sink  to  the 
bottom  of  the  aquarium,  and  swallow  it.  Even  in  the  pigeon  the 
loss  of  the  hemispheres,  which  at  first  induces  a  state  of  profound 
and  seemingly  permanent  lethargy,  is  to  a  great  extent  compensated 
for,  as  time  passes  on,  by  the  unfolding  in  the  lower  centres  of 
capabilities  previously  dormant  or  suppressed.  A  brainless  pigeon 
has  been  known  to  come  at  the  whistle  of  the  attendant  and  follow 
him  through  the  whole  house. 

In  the  mammal  the  removal  of  the  whole  or  the  greater  part  of 
the  cerebral  hemispheres  at  a  single  operation  is  uniformly  and 
speedily  fatal;  even  rabbits  or  rats,  which  bear  the  operation  best, 
survive  but  a  few  hours.  During  those  hours  tliey  manifest 
phenomena  similar  to  those  observed  in  the  bird  and  the  frog.  In 
the  dog  the  entire  cortex  has  been  removed  piecemeal  by  successive 


9i6  THE  CENTRAL  NERVOUS  SYSTEM 

operatioas.  In  this  case,  of  course,  the  change  in  the  condition  of 
the  animal  is  more  gradually  produced,  and  an  opportunity  is 
afforded  for  a  certain  recovery  of  function  in  the  intervals  between 
the  operations.  On  the  whole,  however,  as  might  be  expected 
from  its  greater  intellectual  development,  recovery  is  more  imperfect 
in  the  dog  than  in  the  bird,  much  more  imperfect  than  in  the  frog. 
But  even  in  the  dog  wonderful  resources  lie  hidden  in  the  grey 
matter  of  the  central  neural  axis,  and  are  called  forth  by  degrees 
to  replace  the  lost  powers  of  the  cerebral  cortex.  It  is  true  that  a 
brainless  dog  is  a  less  efficient  animal  than  a  brainless  fish,  or  even 
than  a  brainless  frog;  but  in  favourable  cases,  even  in  the  dog,  the 
movements  of  walking  may  still  be  carried  out  with  tolerable  pre- 
cision in  the  absence  of  the  cerebral  hemispheres.  The  animal  can 
swallow  food  pushed  well  back  into  the  mouth,  although  it  cannot 
feed  itself.  Stupid  and  listless  as  it  is  compared  with  the  normal 
dog,  it  seems  to  be  by  no  means  devoid  of  the  power  of  experiencing 
sensations  as  the  result  of  impressions  from  without,  or  of  carrying 
on  mental  operations  of  a  low  intellectual  grade.  Goltz  had  a  dog 
which  lived  more  than  a  year  and  a  half  practically  without  its 
cerebral  hemispheres,  and  another  which  lived  thirteen  weeks. 
He  believes  that  they  had  lost  understanding,  reflection,  and  memory, 
but  not  sensation,  special  or  general,  nor  emotions  and  voluntary 
power.  Their  condition  may  be  best  described  as  one  of  general 
imbecility.  Hunger  and  thirst  are  present.  They  experience  satis- 
faction when  fed,  become  angry  when  attacked,  see  a  very  bright 
light,  avoid  obstacles,  hear  loud  sounds,  such  as  those  produced 
by  a  fog-horn,  and  can  be  awakened  by  them.  They  are  not  com- 
pletely deprived  of  sensations  of  taste  and  touch.  But  it  ought  to 
be  remembered  that  the  interpretation  of  the  objective  signs  of 
sensation  in  animals  is  beset  with  difficulties;  and  although  every- 
body admits  the  accuracy  of  Goltz's  description  of  what  is  to  be 
seen,  his  interpretation  of  the  facts  has  been  severely  criticized, 
particularly  by  H.  Munk. 

To  the  monkey  there  can  be  no  doubt  that  the  loss  of  the  cerebral 
hemispheres  would  be  a  still  heavier  and  more  irremediable  blow 
than  to  the  dog.  But  nobody  has  yet  succeeded  in  keeping  a 
monkey  alive  after  complete  removal  of  even  one  hemisphere. 

In  man  the  destruction  of  considerable  masses  of  brain-substance, 
particularly  if  gradual,  is  not  necessarily  fatal.  How  great  a  loss 
is  compatible  with  life  cannot  be  exactly  stated.  It  depends  to  a 
large  extent  on  the  position  of  the  lesion.  But  it  is  possible  that 
one  cerebral  hemisphere  may  be  rendered  functionally  useless 
without  immediately  putting  a  term  to  existence.  In  the  foetus, 
however,  no  portion  of  the  great  brain  is  absolutely  indispensable  for 
life  and  movement.  An  anencephalous  foetus  (in  which  the  brain  has 
remained  undeveloped)  may  be  born  alive,  and  live  for  a  short  time 


FUNCTIONS  OF  THIi  BRAIN 


917 


e.n 


We  see,  than,  lliat  liomologous  organs  arc  not  necessarily,  nor 
indeed  usually,  of  the  same  physiological  value  in  different  kinds  of 
animals.  A  loss  which  perhaps  hardly  narrows  the  range  of  the 
psychical,  and  certainly  restricts  only  to  a  sliglit  extent  the  physical 
powers  of  a  fish,  impairs  in  a  marked  degree  the  voluntary  move- 
ments of  a  dog,  in  addition  to  cutting  off  from  it  a  great  part  of  its 
intellectual  life,  and  is  in  man  incompatible  with  life  altogether. 

The  results  of  the  removal  of  the  entire  cerebral  hemispheres  help 
us  to  fix  their  position  as  a  whole  in  the  physiological  hierarchy.  A 
more  minute  analysis  shows  us  that  the  cerebral  cortex  itself  is  not 
homogeneous  in  function,  that  certain  regions  of  it  have  been  set 
aside  for  special  labours. 
Our  knowledge  of  this 
localization  of  function  in 
the  cerebral  cortex  has  been 
derived  partly  from  clinical, 
coupled  with  pathological 
observations  on  man,  and 
partly  from  the  results  of 
the  removal  or  stimulation 
of  definite  areas  in  animals. 
In  addition,  the  study  of 
the  development  of  the 
myelin  sheath,  and  especi- 
ally in  recent  years  the 
minute  study  of  the  hist- 
ology of  the  various  regions, 
have  aided  materially  in 
mapping  out  the  cortex. 

It  is  a  fact  which  might 
appear  strange  and  ahnost 
inexpUcablc  did  the  history 
of  science  not  constantly 
present  us  with  the  hke,  that 
fifty  years  ago  the  universal 
opinion  among  physiologists, 
pathologists,  and  physicians 

was  that  the  cerebral  cortex  is  inexcitable  to  artificial  stimuli,  that 
no  x'isiblc  response  can  be  obtained  from  it.  Tlie  great  names  of 
Flourens  and  IMagendie  stood  sponsors  for  this  error,  and  repressed 
research.  In  1870,  however,  Hitzig  and  Fritsch  showed  tltat  not  only 
was  it  po.ssibIe  to  elicit  muscular  contractions  by  stimukition  of  the 
cortex  of  the  brain  in  the  dog  with  voltaic  currents,  but  that  the 
excitable  area  occupied  a  definite  region  in  the  neighbourhood  of  the 
crucial  sulcus  or  sulcus  centralis,  which  runs  out  over  the  convexity  of 
the  honiispliiTOs  nearly  at  right  angles  to  the  longitudinal  fissure.  In 
this  region  they  were  further  able  to  isolate  several  distinct  areas, 
stimulation  of  which  was  followed  by  movements  respecti\ely  of  the 
head,  face,  neck,  hind-leg,  and  fore-leg  (Fig.  367).  This  was  the 
starting-point  of  a  long  series  of  researches  by  Ferrier,  Munk,  Horsley, 


Fig.  367. — Motor  Areas  of  Dog's  Brain,  n.  neck ; 
f.l.,  fore-limb;  h.L,  hind-limb;  t,  tail;/,  face; 
C.S.,  crucial  sulcus;  g.m.,  eye  movements;  p, 
dilatation  of  the  pupil  in  both  eyes,  but  espe- 
cially in  the  opposite  eye.  All  the  areas  are 
marked  in  the  figure  only  on  the  left  side 
except  the  eyi  rrj  is,  whose  position,  to  avoid 
confusion,  is  indicated  on  the  right  hemi- 
sphere. 


9i8 


THE  CENTRAL  NERVOUS  SYSTEM 


c.m. 


Schafer,  Heidenhain,  and  many  others,  on  the  brains  of  monkeys  as 
well  as  dogs — researches  which  have  formed  the  basis  of  an  exact 
cortical  localization  in  the  brain  of  man,  and  have  enriched  surgery 
with  a  new  province.  In  these  later  experiments  the  interrupted  cur- 
rent from  an  induction  machine  has  been  found  the  most  suitable  form 
of  stimulus  (see  Practical  Exercises,  p.  962),  especially  when  one  elec- 
trode only  is  placed  on  the  cortex  and  the  other  on  some  indifferent 
part  of  the  body — e.g.,  in  the  rectum  (unipolar  stimulation),  a  pro- 
cedure which  permits  of  finer 
localization  than  when  both 
electrodes  are  applied  to  the 
brain  (bipolar  stimulation). 

'  Motor  '  Areas.* — These 
have  been  localized 
with  great  care  (both  by 
stimulation  and  by  removal 
of  portions  of  the  cortex) 
in  the  brains  of  the  higher 
apes  (gorilla,  orang,  and 
chimpanzee)  by  Sherrington 
and  Griinbaum,  and  there 
can  be  no  doubt  that  the 
results,  in  their  general 
outlines  at  least,  can  be 
applied  to  the  human  brain. 
These  observers  employed 
the  so-called  unipolar 
method  of  stimulation. 

The  '  motor  '  region  in- 
cludes the  whole  length  of 
and  the  whole  of  the  free 
width  of  the  precentral 
or  ascending  frontal  con- 
volution, and  dips  down  to 
the  bottom  of  the  central 
sulcus  (fissure  of  Rolando 
in  man),  but  does  not 
extend  behind  the  sulcus.  It  extends  also  into  the  depth  of  all  the 
fissures,  so  that  the  hidden  part  of  the  excitable  area  probably 
equals,  perhaps  exceeds,  the  part  which  is  free  on  the  surface  of  the 
hemisphere.     The  anterior  limit  of  the  '  motor  '  field  is  not  quite 

*  Since  the  so-called  '  motor  '  area,  as  is  now  well  known,  is  really  sensori- 
motor, and  a  region  having  to  do  purely  with  the  discharge  of  motor  impulses 
does  not  exist,  it  would  be  better  to  call  it  the  sensori-motor,  or,  following 
Bastian's  suggestion,  the  kinaesthetic  area.  Probably,  however,  the  altera- 
tion of  a  term  so  long  sanctioned  by  custom  in  physiological  writings  would 
lead  to  confusion.  Accordingly,  in  what  follows  the  word  '  motor  '  will  be 
retained,  but  to  show  that  it  is  used  in  a  special  sense  it  will  be  enclosed  in 
quotation  marks. 


Fig.  368. — Dog's  Brain  with  Lesion.  A  portion 
of  the  cortex  ijulicated  by  the  shaded  area 
was  destroyed  by  cauterization.  The  symp- 
toms were  complete  blindness  of  the  opposite 
eye  (in  this  case  the  right);  weakness  of  the 
muscles  of  the  limbs  and  of  the  neck  on  the 
right  side;  slight  weakness  of  the  limbs  on  the 
left  side.  When  the  animal  walked,  there  was 
a  tendency  to  turn  to  the  left  in  a  circle.  In 
eating  or  drinking,  the  head  was  turned  to  the 
left,  so  that  the  mouth  was  oblique,  and  the 
right  angle  of  the  mouth  was  lower  than  the 
left.  The  tail  movements  were  normal,  and 
there  was  no  deviation  of  the  tail  to  one  side. 


FUNCTIONS  OF  THE  BRAIN 


919 


sharp,  but  shades  off  somewhat  gradually  into  inexcitable  cortex. 
The  sulci  in  this  region  cannot  be  considered  to  represent  physio- 
logical boundaries,  and  they  vary  so  much  in  these  higher  brains, 
that  they  can  easily  prove  fallacious  landmarks.  On  the  mesial 
surface  of  the  hemisphere  the  '  motor '  area  does  not  extend  quite 
to  the  calloso-marginal  fissure. 

Within  this  area  are  localized  movements  of  the  leg  and  arm  and 
their  various  joints,  of  the  head,  face,  mouth,  tongue,  ear,  nostril, 
and  vocal  cords,  of  the  neck,  chest,  and  abdominal  wall,  of  the  pelvic 
floor,  and  the  anal  and  vaginal  orifices. 

Toes,  y  SuJjCUf9_,._  Abdomen 

Ankl^ 

ShouCder 


WrisC 
<J  t humble  ^ 


Ear/ 

^^'t  /  CUdsure 


afja.w. 


Opening 

afja.^      Voca.i  \ 

cords.     ^ThsHcaZion 


Sulcus  eerUraUa. 


CIS  del. 


Fig.  369. — '  Motor  '  Area  of  Cortex  of  Chimpanzee  (Griinbaum  and  Sherrington). 
Lateral  aspect  of  the  hemisphere. 

The  arrangement  of  the  various  regions  follows  very  closely  the 
order  of  the  cranio-spinal  nerves,  which  supply  them,  but  the  organs 
whose  nerves  come  off  lowest  down  are  represented  highest  up  in 
the  '  motor  '  area.  Figs.  369,  370  will  make  this  clear.  In  the  frontal 
region,  isolated  from  the  '  motor  '  area  by  a  strait  of  inexcitable 
cortex,  lies  an  area  the  stimulation  of  which  causes  conjugate  devia- 
tion of  the  eyes.  But  the  reaction  differs  from  that  obtamed  on 
excitation  of  the  '  motor  '  area  proper  in  front  of  the  Rolandic  fissure. 

It  is  to  be  particularly  noted  (i)  that  within  the  larger  areas,  such 
as  those  of  the  arm  and  leg,  smaller  foci  can  be  mapped  off  which 
are  related  to  movements  of  the  separate  joints — thus,  in  the  leg 
area,  the  hip,  knee,  and  ankle-joints,  and  the  great  toe,  are  repre- 


920 


THE  CENTRAL  NERVOUS  SYSTEM 


sented  by  separate  and  special  centres;  (2)  that  stimulation  of  any 
one  of  these  areas  leads,  not  to  contraction  of  individual  muscles, 
but  to  contraction  of  muscular  groups  which  have  to  do  with  the 
execution  of  definite  movements. 


Sulc  Central 


Sulccalioso 

SuJyC.parUlo 
occip 


/  SutcprecenCrmarg 


Sv.bc.  calcarin 


C  S  S  dd. 


Fig. 


370. — 'Motor'  Area  ou  Mesial  Surface  of  Hemisphere:  Brain  of  a  Chimpanzee 
(Troglodytes  Niger)  (Grijnbaum  and  Sherrington).  Left  hemisphere:  mesial  sur- 
face. The  extent  of  the  '  motor  '  area  on  the  free  surface  of  the  hemisphere  is 
indicated  by  the  black  stippling.  On  the  stippled  area  '  LEG  '  indicates  that 
the  movements  of  the  lower  limb  are  represented  in  all  the  regions  of  the  '  motor  ' 
area  visible  from  this  aspect.  The  minuter  subdivisions  in  this  area  overlap 
each  other  so  much  that  no  attempt  is  made  to  distinguish  them  in  the  diagram. 
'  Anus  and  vagina  '  indicates  the  position  from  which  perineal  movements  can 
be  primarily  elicited.  Side,  central.  =  central  fissure;  Sulc.  calcarin.  =  calcarine 
fissure;  Sulc.  parieto  occ/^.  =parieto-occipital  fissure;  SmZc.  calloso  >«flrg.=  calloso- 
marginal  fissure;  Side,  precentr.  marg.  =  preccntral  marginal  fissure.  The  single 
italic  letters  mark  spots  whence,  occasionally  and  irregularly,  movements  of  the 
foot  and  leg  (//),  of  the  shoulder  and  chest  (s),  and  of  the  thumb  and  fingers  (/j). 
have  been  evoked  by  strong  faradization.  The  shaded  area  marked  '  EYES  ' 
indicates  a  field  of  free  surface  of  cortex  which,  under  faradization,  yields  con- 
jugate movements  of  the  eyeballs.  The  conditions  under  which  these  reactions 
are  obtained  separates  them  from  those  characterizing  the  '  motor  '  area. 

The  Stability  of  the  Reactions  obtained  by  Stimulating  Cortical  Points. 

— The  question  whether  stimulation  of  a  '  motor '  area  or  point  invariably 
causes  the  same  movements,  when  it  causes  anj'  movements  at  all,  has 
been  recently  investigated  by  Graham  Brown  and  Slierrington.  They 
observed  the  contractions  of  two  isolated  antagonistic  muscles  acting 
on  the  elbow-joint  (in  monkeys)  after  elimination  of  all  the  other 
muscles  of  the  arm  and  shoulder  by  seotion  of  their  '  motor '  nerves,  when 
a  point  on  the  area  of  the  cortex  in  which  the  movements  of  the  elbow 
are  represented  was  excited  by  the  unipolar  method.  They  find  Miat 
a  cortical  point  which  has  given  flexion  at  the  elbow,  sometimes  on 


FUNCTIONS  OF  THE  BRAIN  921 

investigation  tlic  next  day,  may  give  the  opposite  result  of  extension  cA 
the  elbow.  Even  within  short  intervals  reversal  of  the  reaction  elicited 
from  one  and  tlic  same  point  may  be  seen.  They  do  not  question  at  all 
the  general  regularity  of  the  results  which  such  cortical  points  give 
when  investigated  by  suitable  methods  after  sufficient  intervals  of  rest, 
and  on  which  the  current  statements  as  to  the  reactions  elicited  from 
the  various  '  motor'  areas  are  based.  But  they  see  in  the  influence  of 
transient  excitation  either  of  the  point  itself  or  of  other  more  distant 
points  in  modifying  or  reversing  the  reaction  an  indication  that  one 
of  the  functions  of  the  cortex  may  be  the  carrying  out  of  such  phe- 
nomena of  reversal,  a  function  which  may  play  some  part  in  the 
co-ordination  of  voluntary  movements. 

Inhibition  from  the  Cortex. — Contraction  is  not  the  only  effect  on 
the  muscles  which  can  be  elicited  by  stimulating  the  cortex.  Cor- 
tical inhibition  of  tonus  and  of  active  contraction  is  just  as  char- 
acteristic, though  not  so  obvious  a  result.  There  is  abundant  evidence 
of  reciprocal  innervation  of  volitional  movements  from  the  cortex. 
When,  e.g.,  the  part  of  the  arm  area  which  presides  over  extension 
of  the  elbow  is  stimulated  (in  tlie  monkey),  it  can  be  shown  that  the 
biceps  relaxes  as  the  triceps  contracts.  In  like  manner,  stimulation 
of  the  appropriate  part  of  the  leg  area  will  cause  along  with  contrac- 
tion of  the  extensors  of  the  hip  relaxation  of  such  flexors  as  the  psoas- 
iliacus  and  the  tensor  jascicB  femoris.  Such  observations  are  most 
easily  made  when,  in  a  certain  stage  of  narcosis,  the  limbs,  instead 
of  hanging  limp,  assume  a  position  of  tonic  flexion,  especially  at  the 
elbow  and  hip.  Under  other  conditions  the  position  of  tonic  exten- 
sion of  a  joint  may  be  assumed,  and  then  it  can  be  shown  that  excita- 
tion of  the  appropriate  focus  for  flexion  of  that  joint  will  cause 
simultaneous  contraction  of  the  flexors  and  relaxation  of  the 
extensors. 

The  observer  cannot  fail  to  be  struck  with  the  general  resem- 
blance between  these  cortical  reactions  and  their  co-ordination  and 
the  co-ordinated  bulbo-spinal  reflex  movements  previously  studied. 
There  are,  however,  certain  differences  which  place  the  cortical 
reactions  upon  a  higher  level.  One  of  the  most  important  is  the 
part  played  by  visual,  auditory,  and  pure  '  touch  '  stimuli  in  eliciting 
cortical  motor  responses — e.g.,  '  the  closure  of  the  hand,  pricking 
of  the  ear,  opening  of  the  eyes,  and  turning  of  the  head  in  the 
direction  of  the  gaze  '  (Sherrington).  The  facility  of  response  to 
stimuH  acting  from  a  distance  through  the  distance-receptors,  such 
as  those  of  the  retina  and  labyrinth,  is  one  of  the  great  characteristics 
of  the  cerebrum  as  an  organ  concerned  in  movements,  and  helps 
to  place  the  '  motor  '  cortex  at  the  helm,  since  these  distance- 
receptors  control  more  than  others  the  skeletal  musculature  as  a 
whole.  Spinal  rellex  movements  are  mainly  such  as  are  elicited 
by  harmful  (nocuous)  stimuli  (protective  reflexes),  or  through  the 
sexual  skin  nerves,  or  from  the  visceral  afferent  fibres,  or  such  as 
are  concerned  in  the  chief  movements  of  locomotion. 


922  THE  CENTRAL  NERVOUS  SYSTEM 

Decerebrate  Rigidity  is  a  phenomenon  closely  related  to  the  in- 
hibitory function  of  the  cerebral  cortex.  It  is  a  condition  of  pro- 
onged  spasm  of  certain  groups  of  skeletal  muscles  (especially  the 
retractor  muscles  of  the  head  and  neck,  the  elevators  of  the  jaw 
and  tail,  and  the  extensors  of  the  elbow,  knee,  shoulder,  and  hip), 
supervening  on  removal  of  the  cerebral  hemispheres  by  transection 
anywhere  in  the  mid-brain  or  in  the  posterior  part  of  the  thalamus, 
and  favoured  by  suspending  the  animal  in  the  vertical  posture. 
If  the  afferent  roots  belonging  to  one  of  the  rigid  limbs  are  severed, 
it  at  once  becomes  flaccid,  while  the  other  limbs  remain  rigid.  The 
tonus  is  therefore  reflex  through  the  local  afferent  nerves,  and,  to 
be  more  precise,  through  those  that  supply  the  deep  structures 
(joints,  muscles,  etc.).  The  centre  must  be  situated  somewhere 
between  cerebrum  and  spinal  bulb,  since  section  of  the  bulb 
abolishes  the  rigidity.  It  is  not  apparently  in  the  cerebellum.  It 
is  noteworthy  that  the  muscles  mainly  involved  in  decerebrate 
rigidity  are  those  which  are  much  more  easily  inhibited  than  excited 
from  the  '  motor  '  cortex,  and  also  in  the  local  spinal  reflexes.  After 
removal  of  the  cerebrum,  the  mechanism  which  maintains  their 
tonic  contraction  has  free  play.  Sherrington  points  out  that  this 
mechanism  sustains  the  steady  muscular  tension  necessary  to  pre- 
serve against  the  force  of  gravity  the  attitude  or  posture  of  the  body. 
When  the  transient  spinal  reflex  or  the  transient  cortical  effect 
breaks  in  upon  this  tonic  contraction — e.g.,  in  locomotion — inhibi- 
tion of  the  contracted  extensors  accompanies  contraction  of  the 
flexors  (see  also  p.  911). 

Removal  of  a  single  '  motor '  region  leads  to  paralysis  of  the 
corresponding  limb,  or  part  of  a  limb,  on  the  opposite  side.  For 
example,  after  extirpation  of  the  hand  area  the  hand  is  for  a  few 
days  practically  useless  and  apparently  powerless.  In  a  few  weeks, 
however,  it  recovers  remarkably,  so  that  it  is  once  more  used  in 
climbing  or  in  conveying  food  to  the  mouth.  It  is  an  important 
question  in  what  way  this  recovery  is  brought  about.  If  the  whole 
of  the  corresponding  area  in  the  opposite  hemisphere  is  now  removed, 
a  similar  paralysis  occurs  in  the  other  hand,  but  the  hand  whose 
'  motor  '  area  was  first  extirpated  remains  entirely  unaffected  by  the 
second  lesion.  On  the  contrary,  the  first  hand  is  used  more  freely 
and  more  adroitly  than  before  the  second  operation,  probably  be- 
cause the  animal  needs  to  use  it  more.  The  second  hand  recovers 
eventually,  like  the  first.  If  when  this  has  taken  place  the  remain- 
ing part  of  the  arm  area  from  which  the  hand  area  was  first  excised 
be  removed,  neither  hand  is  apparently  affected,  although  there  is 
severe  paralysis  of  the  shoulder  and  slighter  paralysis  of  the  elbow 
on  the  side  opposite  to  the  lesion,  which  is  again  largely  recovered 
from.  The  recovery  of  the  hand  movement  cannot  therefore  be 
attributed  to  the  taking  on  of  the  function  of  the  corresponding 


FUNCTIONS  OF  THE  DRAIN 


923 


'  motor  '  area  either  by  the  opposite  hand  area  or  by  the  adjacent 
'  motor '  cortex  of  the  same  hemisphere.  According  to  some 
authorities,  the  recovery  is  due  to  the  representation  of  the  upper 
limb  in  the  post-central  gyrus  (ascending  parietal  convolution  in 
man)  acting  through  fibres  that  descend  from  this  gyrus  to  the 
optic  thalamus,  and  thence  through  the  rubro-spinal  tract,  which 
runs  to  the  spinal  cord  (p.  839). 

Removal  of  the  whole  of  the  '  motor  '  cortex  of  one  hemisphere, 
in  such  animals  as  this  operation  has  been  performed  on,  causes 
paralysis  of  movement  on  the  opposite  side  of  the  body.  The 
paralysis  is  less  marked  in  the  case  of  bilateral  muscles  that  habitu- 
ally act  together  than  in  the  case  of  those  which  ordinarily  act  alone. 
Thus  the  muscles  of  respiration  and  the  muscles  of  the  trunk  in 


Fig.  371. — Cerebral  Cortex  Man  (seen  from  Above).  The  front  of  the  brain  is  towards 
the  left.  The  dotted  line  shows  the  position  of  the  fissure  of  Rolando,  as  fixed 
by  Thane's  rule  (p.  929). 

general  are,  although  perhaps  weakened,  never  completely  para- 
lyzed. This  is  an  indication  that  each  member  of  such  functional 
pairs  of  muscles  is  innervated  from  both  hemispheres;  and  this 
physiological  deduction  is  supported  by  the  anatomical  fact  already 
referred  to,  that  after  removal  of  the  '  motor  '  cortex,  or  injury  to 
the  pyramidal  tracts  in  the  internal  capsule  or  crus,  some  degener- 
ated fibres  (homolateial  fibres)  are  found  in  the  crossed  pyramidal 
tract  on  the  side  of  the  lesion  (p.  847). 

In  the  dog  after  a  time  the  paralysis  may  more  or  less  completely 
disappear.     In  the  monkey  restoration  is  less  complete. 

Some  interesting  observations  have  been  made  on  a  monkey, 
which  was  carefully  watched  for  eleven  years  after  the  removal  by 
two  operations  of  the  cortex  of  the  greater  portion  of  the  frontal 


924  THE  CENTRAL  NERVOUS  SYSTEM 

and  parietal  lobes  on  the  left  side.  The  character  of  the  animal, 
which  had  been  studied  for  months  before  the  operations,  was  en- 
tirely unaffected.  All  its  traits  remained  unaltered.  There  was  no 
loss  of  memory  or  intelligence.  On  the  other  hand,  disturbances 
of  movement  on  the  right  side  were  very  noticeable  up  till  its  death. 
It  learned  again  to  use  the  right  limbs  in  locomotion;  but,  although 
they  were  not  markedly  weaker  than  those  of  the  left  side,  their 
movements  had  a  certain  clumsiness,  which  was  associated  with  a 
permanent  diminution  in  the  sensibility  of  the  skin  of  these  limbs. 
Muscular  sensibility  was  also  lessened.  In  acts  requiring  the  use  onlj' 
of  one  hand,  the  right  was  never  willingly  employed,  and  it  evidently 
cost  the  animal  a  great  effort  to  use  it  in  such  movements,  but  by 
special  training  it  learnt  again  to  give  the  right  hand  when  asked 
for  it,  and  to  make  use  of  it  for  other  purposes.  The  movements 
with  which  the  '  motor  '  areas  are  concerned  are  essentially  skilled 
movements,  and  we  may  suppose  that  it  is  more  difficult  for  a 
monkey  to  educate  again  a  centre  for  such  complex  and  elaborate 
manoeuvres  as  are  performed  by  fts  hand  than  for  a  dog  to  regain 
normal  control  of  the  comparatively  simple  movements  of  its  paw. 
In  man  in  cases  of  hemiplegia,  when  the  patient  lives  for  some  time, 
a  certain  amount  of  recovery  usually  takes  place,  especially  in  young 
persons,  in  the  paralyzed  leg,  but  much  less  in  the  paralyzed  arm. 

In  the  lower  monkeys  the  '  motor  '  area  was  formerly  stated  to 
extend  behind  the  sulcus  centralis  into  what  in  man  would  be  called 
the  ascending  parietal  convolution  (post-central  gyrus),  and  also  to 
be  more  extensively  represented  on  the  mesial  surface  of  the  hemi- 
sphere than  in  the  higher  apes.  Such  observations,  however,  require 
to  be  reinterpreted  in  view  of  the  results  of  Sherrington  and  Griin- 
baum,  especially  as  they  were  carried  out  by  the  bipolar  method  of 
stimulation,  with  both  electrodes  on  the  cortex.  This  method  does 
not  admit  of  such  strict  locahzation  of  the  stimulus  as  the  unipolai 
method.  The  most  recent  work  with  the  unipolar  method  has 
indicated  that  in  the  lower  apes  also  excitation  of  the  gyrus  post- 
centralis  does  not  cause  movements  (C.  and  O.  Vogt). 

It  is  in  the  light  of  the  results  obtained  in  monkeys,  and  by  the 
aid  of  histological,  embryological,  clinical,  and  pathological  ob- 
servations, that  the  '  motor  '  areas  in  man  have  to  a  great  extent 
been  mapped  out. 

The  histological  differentiation  of  the  various  cortical  regions  recently 
demonstrated  by  Brodmann  and  by  Campbell  are  of  especial  interest 
(Figs.  37--376).  It  has  long  been  customarj-  to  divide  the  cortex  into 
layers,  although  the  number  and  the  boundaries  of  these  layers  are 
somewhat  arbitrarily  fixed.  Brodmann  distinguishes  six  layers:  (i)  A 
zonal  or  peripheral  layer,  containing  many  nerve-fibres  and  neuroglia 
cells,  but  few  nerve-cells;  (2)  a  layer  containing  '  granules  '  and  small 
pyramidal  cells  {external  granular  layer) ;  (3)  a  layer  of  medium  and 
large  pyramidal  cells  {pyramidal  layer) ;    (4)  a  layer  of  small  irregular 


FUNCTIONS  OF  THE  BRAIN 


925 


cells  {internal  granular  or 
stellate  layer) ;  (5)  a  '  gang- 
lionic '  layer,  containing  the 
largest  pyramidal  cells  {deep 
large  pyratnids);  (6)  a  layer 
{lamina  mnl(ijormis)  uf 
spindle-shaped  or  polymor- 
])hous  cells.  These  layers 
vary  in  their  structural  de- 
tails, and  especially  in  their 
relative  development  in 
arimals  of  dilTerent  rank  in 
the  mammalian  scale,  in  one 
and  the  same  animal  at 
different  periods  in  its  em- 
br^^-onic  and  extra  -  uterine 
growth,  and  also  in  different 
parts  of  the  cortex  in  an  adult 
animal  of  given  species.  The 
region  in  front  of  the  central 
sulcus  (fissure  of  Rolando)^ 
e.g.,  is  characterized  by  the 
presence  of  the  giant  pyra- 
mids of  Betz,  which  give 
origin  to  the  pyramidal  fibres 
going  to  the  trunk  and  limbs 
(Fig-  373)- 


\\\  ■ 

W 

.  I 

16',' 


•     .1' 

J  !  ■■ 


k 

B 


Fig.  372. — Cell-Lamination  of  Gyrus  Postcen- 
tralis  (Campbell).  A,  just  behind  upper  end 
of  fissure  of  Rolando;  B,  from  the  posterior 
edge  of  the  gyrus  (intermediate  postcentral 
area  of  Campbell). 


J,  • . 

r  . 


.•  4 


5IV  ^:::;:.f^^  V* 


Fig.  373. — Cell-Lamination  of  Cyrus  Pre. 
centralis  (Campbell).  From  the  portion 
of  the  gyrus  immediately  in  front  of  the 
central  sulcus  (Campbell's  precentral 
area  in  Figs.  375,  376). 


Fig.  374- — Cell-La'iuiiatioTi  uf  (iyrus 
Precentralis  (Campbell).  From  an- 
terior part  of  the  g>'rus  (Campbell's 
intermediate  precentral  area  in 
Figs.  375.  376). 


Although  the  results  arc  less  definite,  the  work  of  Flechsig  on  the 
time  of  development  of  the  medullary  sheath  of  the  fibres  in  the  various 
cerebral  convolutions  has  also  contributed  to  our  knowledge  of  localiza- 


926 


THE  CENTRAL  NERVOUS  SYSTEM 


Tii^P* 


Fig-  375. — Structurally  Differentiated  Cortical  Areas  (Campbell).     External  surface 
of  hemisphere  (human  brain). 


Fig.  376. — Structurally  Differentiated  Cortical  Areas  (Campbell).     Mesial  surface  of 
hemisphere  (human  brain). 


FUNCTIONS  OF  THE  BRAIN 


927 


tion  in  the  cortex.  In  the  development  of  a  neuron  four  stages  can  be 
distinguished:  (i)  Cells  without  processes;  (3)  the  appearance  of  pro- 
cesses, first  the  axon  and  then  the  dendrites;  (3)  the  formation  of  col- 


Fig.  377. — Flechsig's  Developmental  Zones  (after  Flechsig).  Outer  surface  of  human 
cerebral  hemisphere.  Primary  zones  (i-io),  darkly  shaded;  intermediate  zones 
(11-31),  less  deeply  shaded;  terminal  zones  (32-36),  unshaded. 

laterals;   (4)  myelination  or  the  formation  of  the  medullary  sheath 
(Fig.  323.  P-  826). 

Myelination  occurs  in  the  cerebral  convolutions  in  a  regular  order. 
In  some  areas  the  fibres  may  be  medulla  ted  three  months  before  birth, 


Fig.  378.— Flechsig's  Developmental  Zones  (after  Flechsig).     Inner  surface  of  human 
cerebral  hemisphere. 

in  others  not  till  six  months  later.  For  instance,  the  Rolandic  and 
olfactory  regions,  the  calcarine  portion  of  the  occipital  lobe  associated 
with  vision,  and  the  portion  of  the  temporal  lobe  associated  with 
hearing,  are  plentifully  provided  with  medullated  fibres  a  short  time 
after  birth,  at  any  rate  before  the  first  month,  whereas  the  remaining 
regions  of  the  cortex  are  completely,  or  almost  completely,  free  from 


928  THE  CENTRAL  NERVOUS  SYSTEM 

sucli  fibres.  In  this  way  Flechsig  has  distinguished  thirty-six  cortical 
fields  (Figs.  377,  37S),  which  he  divides  according  to  the  time  of 
myelination  into  three  groups: 

1.  Primary  fields,  ten  in  number,  which  are  well  provided  with  mye- 
linated fibres  at  birth.  They  include  the  cortical  centres  for  the 
various  sensations  and  also  the  '  motor  '  area.  They  are  connected 
especially  with  the  so-called  projection  fibres.  Thus,  the  cutaneous 
and  muscular  sense  is  assumed  to  be  represented  in  field  i,  the  sense 
of  smell  in  field  2,  of  vision  in  4,  and  of  hearing  in  5.  From  field  i 
arise  the  fibres  of  the  pyramidal  tract,  chiefly  from  the  ascending 
frontal  convolution,  while  the  sensory  fibres  from  the  skin  and  muscles 
end  mainly  in  the  ascending  parietal.  This  is  an  illustration  of  what 
Flechsig  considers  a  general  rule  for  these  primary  fields — viz.,  that 
each  primordial  sensory  region  is  connected  both  with  an  afferent 
(cortici-petal)  and  with  an  efferent  (cortici-fugal)  tract.  From  the 
visual  area  (4),  e.g.,  arises  a  tract  which  proceeds  mainly  to  the  anterior 
corpus  quadrigeminum. 

2.  Terminal  fields  (32  to  36  in  the  figures)  which  become  myelinated 
late,  the  process  not  beginning  until  at  least  a  month  after  birth. 

3.  Intermediate  fields  (11  to  31)  which  become  myelinated  earlier 
than  the  terminal,  but  later  than  the  primary.  The}^  and  the  terminal 
fields  constitute  par  excellence  association  centres,  which  furnish  fibres 
(association  fibres)  connecting  the  centres  represented  in  the  priniary 
fields — e.g.,  such  fibres  as  must  be  continually  conveying  impressions 
from  the  visual  centre  to  the  '  motor '  cortex  when  the  hand  is  sketching 
a  landscape.  It  may  also  be  considered  a  function  of  these  association 
centres  to  store  up  the  memories  of  previous  sense  impressions.  Flech- 
sig divides  the  association  centres  represented  in  the  terminal  fields 
into — (i)  The  great  anterior  association  centre  in  the  frontal  lobe  in 
front  of  the  '  motor  '  area;  (2)  the  great  posterior  association  centre  in 
the  parieto-temporal  region;  (3)  the  smaller  middle  or  insular  associa- 
tion centre,  which  coincides  with  the  island  of  Reil,  an  area  which, 
according  to  Sherrington  and  Criinbaum,  is  totally  '  inexcitable  '  as 
regards  the  production  of  movement  in  the  anthropoid  apes.  These 
association  centres  are  foci,  from  which  issue  and  to  which  come  the 
long  association  paths.  The  reader  must  bear  in  mind  that  Flechsig's 
conclusions  as  to  the  functions  of  his  very  numerous  areas  are  in  many 
cases  hypothetical,  and  can  only  be  accepted  when  corroborated  by 
other  methods.  We  are  far  from  being  able  at  present  to  subdivide 
the  functions  of  the  cortex  so  minutely  as  is  suggested  by  his  map. 

Clinical  and  Pathological  Observations  in  man  agree,  upon  the 
whole,  with  wonderful  precision  with  the  results  of  experiments  on 
animals ;  and,  indeed,  before  any  experimental  proof  of  the  minute 
and  elaborate  subdivision  of  the  cortex  had  been  obtained,  Broca 
had  already,  from  the  phenomena  of  the  sick-bed  and  the  post- 
mortem room,  located  a  centre  for  speech  in  the  left  inferior  frontal 
convolution  (but  see  p.  936),  and  Hughlings  Jackson  had  associated 
pathological  lesions  of  the  Rolandic  area  with  certain  cases  of  epi- 
leptiform convulsions. 

An  extensive  haemorrhage  involving  the  Rolandic  area  of  the 
cerebral  cortex,  or  an  embolus  blocking  the  middle  cerebral  artery, 
causes  paralysis  of  the  opposite  side  of  the  body.  An  embolus  of  a 
branch  of  the  middle  cerebral  artery  causes  paralysis  of  the  muscles. 


FUNCTIONS  OF  THE  BRAIN  929 

or  rather  movements,  represented  in  the  area  supphed  by  it.  A 
tumour  causes  symptoms  of  irritation,  motor  or  sensory — convul- 
sions beginning  in,  or  sensations  referred  to,  the  parts  represented 
in  the  regions  on  which  it  presses.  In  connection  with  the  locaHza- 
tion  of  lesions  in  the  '  motor  '  area  of  the  cortex,  and  operative 
interference  for  their  cure,  the  cortex  has  been  frequently  stimulated 
in  man.  There  is  no  doubt  that  the  '  motor  '  region  corresponds 
closely  in  position  to  that  of  the  higher  apes.  It  does  not  include 
the  postcentral  gyrus,  for  stimulation  of  this  convolution  with  such 
strengths  of  current  as  are  permissible  evokes  no  movements,  while 
movements  are  readily  elicited  from  the  precentral  gyrus  (Horsley, 
etc.).  In  exposing  the  '  motor  '  region,  or  any  particular  part  of  it, 
the  exact  position  of  the  fissure  of  Rolando  becomes  important ;  and 
Thane  has  given  the  following  simple  method  for  fixing  it :  The 
point  midway  between  the  point  of  the  nose  and  the  occipital  pro- 
tuberance is  fixed  by  measuring  the  distance  with  a  tape.  The 
upper  end  of  the  fissure  of  Rolando  lies  half  an  inch  behind  this 
middle  point.  The  fissure  makes  an  angle  of  67°  with  the  longi- 
tudinal fissure  (Fig.  371).  The  minor  fissures  are  so  inconstant  as 
to  afford  no  safe  guidance  in  the  localization  of  a  given  area.  This 
must  be  dehmited  by  stimulation. 

Sensory  Functions  of  the  Rolandic  Area. — There  are  many  proofs 
that  the  '  motor  '  region  is  not  a  purely  motor,  but  a  sensori-»ioior, 
or  kincBsthetic,  area.  Histological  and  embryological  studies  on  the 
course  of  the  sensory  paths,  as  already  pointed  out,  support  this 
conclusion.  It  has  also  been  mentioned  that,  according  to  Goltz's 
observations  (p.  916),  removal  of  the  Rolandic  cortex  causes  defects 
of  sensation  as  well  as  of  movement.  In  man,  in  connection  with 
operations  on  the  brain,  still  better  evidence  has  been  obtained. 
In  two  cases  Gushing  was  able  to  elicit  tactile  sensations  by  electrical 
stimulation  of  the  gyrus  postcentralis  (ascending  parietal  convolu- 
tion), and  the  sense  of  muscular  movement  by  electrical  stimulation 
of  the  gyrus  precentralis.  In  a  very  careful  study  of  a  case  in  which 
he  removed  the  upper  limb  area  of  the  right  hemisphere  in  a  boy 
for  violent  convulsive  movements  of  the  whole  of  the  left  arm, 
Horsley  came  to  the  condur-ion  that  the  precentral  gyrus  in  man 
is  the  seat  of  representation  of  (i)  slight  tactile  sensation  (after  the 
operation  appreciation  of  the  lightest  tactile  stimuli  was  lost); 
(2)  topognosis — i.e.,  appreciation  of  the  localization  in  space  of  the 
point  touched;  (3)  muscular  sense;  (4)  stereognosis,  or  the  power  of 
recognizing  the  form  of  objects  touched  and  handled ;  (5)  pain — 
e.g.,  that  caused  by  a  pin-prick;  (6)  volitional  movement.  The 
postcentral  g\Tus  in  man  appears  to  be  the  seat  of  a  similar  sensory 
representation,  but  as  its  relation  to  the  efferent  impulses  concerned 
in  volitional  movements  is  less  decided  than  that  of  the  precentral 
gyrus,  so  its  relation  to  afferent  impulses,  both  from  the  skin  anrl  the 

59 


930  THE  CENTRAL  NERVOUS  SYSTEM 

deeper  structures,  is  better  marked.  From  the  field  of  experiment 
further  evidence  of  the  sensori-motor  nature  of  the  '  motor  '  region 
is  forthcoming- 

(i)  It  has  been  found  that  if  the  posterior  roots  of  the  nerves 
supplying  one  of  the  limbs  be  cut  in  a  monkey,  all  the  most  delicate 
and  skilled  movements  of  the  limb  are  either  greatly  impaired  or 
totally  abolished  (Mott  and  Sherrington).  The  limb  is  not  used  for 
progression  or  for  climbing,  but  hangs  limp,  and  apparently  help- 
less, by  the  side  of  the  animal.  That  this  condition  is  not  due  to 
any  loss  of  functional  power  by  the  peripheral  portion  of  the  motor 
path  may  be  assumed,  since  the  anterior  roots  remain  intact.  That 
it  is  not  due  to  any  want  of  capacity  on  the  part  of  the  '  motor  ' 
centres  to  discharge  impulses  when  stimulated  may  be  shown  by 
exciting  the  cortical  area  of  the  limb — either  electrically  or  by 
inducing  epileptic  convulsions  by  intravenous  injection  of  absinthe 
— when  movements  of  the  affected  limb  take  place  just  as  readily 
as  movements  of  the  sound  limb.  The  cause  of  the  impairment  of 
voluntary  motion,  then,  can  only  be  the  loss  of  the  afferent  impulses 
which  normally  pass  up  to  the  brain,  and  presumably  to  the  '  motor  ' 
cortex.  When  only  one  sensory  nerve-root  is  cut,  no  defect  of  move- 
ment can  be  seen;  and  this  is  evidently  in  accordance  with  the  fact 
previously  mentioned  (p.  863),  that  complete  anaesthesia  of  even  the 
smallest  patch  of  skin  is  never  caused  by  section  of  a  single  posterior 
root.  And  that  it  is  the  loss  of  impulses  from  the  skin  which  plays 
the  chief  part  is  shown  by  the  fact  that  after  division  of  the  posterior 
roots  supplying  the  muscles  of  the  hand  or  foot,  which  only  partially 
interferes  with  the  sensory  supply  of  the  skin,  joints,  sheaths  of 
tendons,  etc.,  movement  is  unimpaired;  while  section  of  the  nerve- 
roots  supplying  the  skin,  those  of  the  muscles  being  left  intact,  causes 
extreme  loss  of  motor  power. 

(2)  If  a  strength  of  stimulus  be  sought  which  will  just  fail  to 
cause  contraction  of  the  muscular  group  related  to  a  given  motor 
area,  and  a  sensory  nerve,  or,  better,  a  sensory  surface  (best  of  all, 
the  skin  over  the  corresponding  muscles),  be  now  stimulated,  con- 
traction may  occur — that  is  to  say,  the  excitability  of  the  motor 
centres  may  be  increased.  This  shows  that  the  '  motor  '  region  is 
en  rapport  not  only  with  efferent,  but  also  with  afferent  fibres,  that 
it  receives  impulses  as  well  as  discharges  them. 

The  same  experiment  is  a  proof  that  the  results  of  excitation  of  the 
motor  cortex  are  due  to  stimulation  of  the  grey  matter,  and  not,  as 
might  be  objected,  of  the  white  fibres  of  the  corona  radiata.  It  is 
undoubtedly  possible  to  excite  these  fibres  by  electrodes  directly 
applied  to  the  motor  cortex,  but  in  the  latter  case  the  current  has  to 
be  made  stronger  than  is  sufficient  to  excite  the  grey  matter  alone. 
Further  evidence  is  afforded  by  the  following  facts:  (a)  The  '  period 
of  delay  ' — that  is,  the  period  which  elapses  between  stimulation  and 
contraction — is  greater  by  nearly  50  per  cent,  when  the  cortex  is  stimu- 


FUNCTIONS  OF  THE  BRAIN 


931 


lated  than  when  tlic  wliite  hbrcs  are  direGtly  excited,  (b)  Morphine 
greatly  increases  the  period  of  delay  for  stimluation  of  the  cortex,  and 
at  the  same  time  renders  the  resulting  contractions  more  prolonged 
than  normal,  while  the  results  of  direct  stimulation  01  the  white  fibres 
are  much  less,  if  at  all,  affected,  (c)  Stimulation  of  the  grey  matter, 
when  separated  from  the  subjacent  white  matter  by  the  knife,  but  left 
in  position,  is  without  effect  unless  the  strength  of  stimulus  be  increased, 
altliough  twigs  of  the  current  ought,  of  course,  to  pass  into  the  corona 
radiata    as    easily    as    before. 

Perfectly  definite   movements  LF  RF  LF  Rf 

can,    however,    be   excited   or  ' 

inhibited  by  stimulating  de- 
finite spots  in  the  corona  radi- 
ata, and  even  in  the  internal 
capsule.  This  simply  means 
that  in  these  positions  the 
fibres  representing  these  move- 
ments are  not  yet  intermingled 
with  fibres  representing  other 
mo\'ements. 

Sensory  Areas — ^Visual  Cen- 
tres.— In  the  occpital  lobe  in 
animals  an  area  of  consider- 
able extent  has  been  found, 
destruction  of  which  causes 
hemianopia  (p.  894).  Thus, 
if  the  right  occipital  cortex  is 
destroyed,  the  right  halves 
of  the  two  retinae  are  para- 
lyzed, and  the  left  half  of  the 
field  of  vision  is  a  blank. 
There  is  conjugate  deviation 
of  the  head  and  eyes  to  the 
same  side  as  the  lesion — in 
other  words,  the  animal  turns 
its  head  and  eyes  to  the  right. 
Destruction  of  this  region  on 
both  sides  causes  complete 
blindness.  When  the  same 
region  is  stimulated,  the  eyes 
and  head  are  turned  to  the 
left — that  is,  there  is  conju- 


Fig.  379. — Diagram  of  Relations  of  Occipital 
Cortex  to  the  Retinae.  RO,  LO,  right  and 
left  occipital  corte.x;  RE,  LE,  right  and  left 
retina;  C,  optic  chiasma;  RF,  LF,  right  and 
left  visual  fields.  The  continuous  lines 
passing  back  from  the  retina;  to  the  occi- 
pital cortex  represent  the  crossed,  the 
broken  lines  the  uncrossed,  fibres  of  the 
optic  nerves  and  tracts.  For  the  sake  of 
simplicity  the  intermediate  stations  on  the 
visual  path  in  the  anterior  corpora  quadri- 
gemina.  lateral  geniculate  bodies,  and  pul- 
vinar  are  not  represented  in  the  diagram. 
For  these  connections,  see  Fig.  360,  p.  894. 


gate  deviation  to  the  opposite 
side.  In  the  higher  monkeys  the  eye  movements  can  be  elicited  only 
from  the  extreme  posterior  apex  of  the  occipital  lobe  and  from  its 
calcarine  region,  and  tlten  not  easily.  The  movements  differ  from 
those  produced  by  stimulation  of  the  area  for  eye  movements  in  the 
frontal  lobe.  They  are  not  so  certain,  their  latent  period  is  longer, 
and  a  stronger  stimulus  is  required  to  evoke  them.     It  cannot  be 


932  THE  CENTRAL  NERVOUS  SYSTEM 

doubted  that  the  occipital  region  is  concerned  in  vision,  and  it  is  a 
very  natural  suggestion  that  the  movements  are  the  result  of  visual 
sensations  in  the  excited  occipital  cortex.  The  right  occipital  lobe 
is  concerned  with  vision  in  the  right  halves  of  the  two  retinae  (Figs. 
360  and  379).  Now,  under  normal  conditions,  a  visual  image  would 
be  cast  on  the  two  right  retinal  halves  b}^  an  object  placed  towards 
the  left  of  the  field.  The  movements  of  the  head  and  eyes  to  the 
left  may  therefore  be  plausibly  explained  as  an  attempt  to  look  at, 
and  a  rotation  towards,  the  supposed  object. 

The  pathological  evidence  is  very  clear  that  disease  of  the  occipital 
lobe,  especially  of  the  cuneus,  a  triangular  area  on  its  mesial  surface, 
causes  hemianopia  in  man.  A  limited  lesion  may  even  be  associated 
with  an  incomplete  hemianopia,  and  cases  have  been  recorded  in  which 
colour  hemianopia  (blindness  of  the  corresponding  halves  of  the  two 
retinae  for  coloured  objects)  co-existed  with  normal  vision  for  white 
light.  The  precise  limits  of  the  occipital  visual  area  are  still  disputed. 
It  probably  occupies,  in  addition  to  the  cuneus,  the  lingual  lobule  and 
a  portion  of  the  external  aspect  of  the  occipital  lobe.  The  question  of 
the  projection  of  the  retina  upon  the  visual  cortex — i.e.,  the  question 
whether  each  retinal  area  is  represented  in  a  definite  cortical  area — 
has  given  rise  to  much  debate.  The  representation  of  the  fovea  cen- 
tralis, the  area  of  most  distinct  vision,  has  aroused  especial  interest. 
It  has  been  asserted  that  a  circumscribed  area  in  the  region  of  the  cal- 
carine  fissure  is  the  centre  for  the  fovea  (Henschen).  But  it  is  totally 
opposed  to  this  view  that  extensive  lesions  of  the  occipital  cortex,  even 
on  both  sides,  do  not,  except  in  rare  cases,  cause  total  blindness  in  the 
foveal  region,  although  peripheral  vision  is  destroyed.  On  the  other 
hand,  in  no  case  has  a  purely  cortical  lesion  been  found  associated  with 
blindness  confined  to  the  fovea  (Monakow).  The  fibres  of  the  optic 
radiation  which  are  on  the  path  from  the  fovea  are  accordingly  dis- 
tributed diffusely  to  the  visual  cortex.  Sometimes  dimness  of  vision  in 
the  whole  of  the  opposite  eye  (crossed  amblyopia),  and  not  hemianopia, 
is  caused  by  a  lesion  of  the  occipital  cortex.  It  seems  impossible  to 
explain  this  and  other  facts  without  postulating  the  existence  of  more 
than  one  visual  centre;  and  it  has  been  supposed  that  in  the  angular 
gjTus  and  the  neighbouring  region  a  higher  visual  centre  exists  which 
is  connected  with  the  lower  occipital  centres  for  the  two  halves  of  the 
opposite  eye.  Thus,  the  right  angular  gyrus  would  be  in  connection 
with  the  part  of  the  right  occipital  cortex  which  has  to  do  with  vision 
in  the  nasal  half  of  the  left  eye,  and  with  the  part  of  the  left  occipital 
cortex  which  has  to  do  with  vision  in  the  temporal  half  of  that  eye. 
This  higher  centre,  which  perhaps  functions  as  a  storehouse  of  visual 
memories,  probably  corresponds  to  the  structurally  differentiated  area 
(visuo-psychic  area  of  Campbell),  as  the  lower  centre  corresponds  to 
his  structurally  differentiated  visuo-sensory  area  (Figs.  376,  377). 

Auditory  Centre. — On  the  outer  surface  of  the  temporo-sphenoidal 
lobe,  mainly  in  the  first  temporal  convolution,  lies  an  area  asso- 
ciated with  the  sense  of  hearing.  Stimulation  in  the  region  of  the 
first  temporal  convolution  may  cause  the  animal  to  prick  up  its  ears 
on  the  opposite  side.  Destruction  of  this  area  on  both  sides  is 
followed  by  complete  and  irremediable  loss  of  hearing.  If  it  is 
destroyed  only  on  one  side,  there  is  partial  deafness  of  the  opposite 


FUNCTIONS  OF  THE  BRAIN 


933 


ear,  and  also  to  some  extent  of  the  ear  on  the  same  side.  This  is 
gra(kia!4y  recovered  from.  If  it  is  destroyed  on  the  left  side  there 
is  also  the  peculiar  condition  called  '  word-deafness,'  which  will  be 
referred  to  directly  (p.  937).  In  deaf-mutes  the  first  temporal 
convolution  may  be  atrophied.  There  is  evidence  that  the  posterior 
corpora  quadrigemina  and  the  mesial  geniculate  body  form  an  in- 
ferior relay  on  the  route  between  the  fibres  of  the  auditory  nerve 
and  the  temporal  cortex.  There  are  indications  that  within  the 
auditory  area  so-called  '  musical  centres  '  exist — that  is,  an  orderly 


Fig.  380. 


-Lateral  View  of  Left  Hemisphere  with  Sensory  Areas:  Man. 
of  the  brain  is  towards  the  left. 


The  front 


arrangement  of  the  cell-bodies  of  the  neurons  that  have  to  do  with 
the  perception  of  pitch,  so  that  a  limited  lesion  may  cause  deafness 
to  notes  of  a  particular  pitch  when  it  is  situated  on  one  part  of  the 
area,  and  deafness  to  notes  of  a  different  pitch  when  it  is  situated 
elsewhere  (T.arionow). 

Centre  for  Smell. — As  to  the  position  of  the  centre  for  smell,  direct 
experiment  on  animals  cannot  teach  us  much,  for  if  the  outward 
tokens  of  visual  and  auditory  sensations  are  dubious  and  fluctuating, 
still  more  is  this  the  case  with  the  signs  of  sensations  of  smell.      A 


934 


THE  CENTRAL  NERVOUS  SYSTEM 


further  source  of  fallacy  is  the  fact  that  other  sensations  than  those 
of  smell  are  caused  by  stimulation  of  the  mucous  membrane  of  the 
nose.  Substances  like  ammonia,  for  example,  affect  entirely  the 
endings  of  the  trigeminus,  which  is  the  nerve  of  common  sensation 
for  the  nostrils.  Pathological  and  clinical  evidence  would  be  of  great 
value,  but  it  is  as  yet  scanty,  and  of  itself  indecisive.  Some  cases 
of  epilepsy  have  been  reported  in  which  the  attack  was  heralded  by 
smells  for  which  there  was  no  objective  cause.  At  necropsy  the  un- 
cinate gyrus  was  found  diseased.  So  far  as  it  goes,  such  evidence 
supports  the  view  derived  from  the  anatomical  connections  of  the 
olfactory  tracts,  that  the  centre  for  smell  is  situated  in  the  uncinate 
g^Tus  on  the  mesial  aspect  of  the  temporal  lobe,  for  the  olfactory 
track  may  be  traced  into  this  region.  In  animals  with  a  very  acute 
sense  of  smell,  this  gyrus  is  magnified  into  a  veritable  lobe,  called 
from  its  shape  the  pyriform  lobe;  from  its  supposed  function,  the 


Fig.  381.- 


-Sensory  Areas  of  Mesial  Surface  of  Human  Brain.    The  front  of  the  brain 
is  towards  the  right. 


rhinencephalon.  The  centre  for  taste  is  supposed  to  be  situated  in 
the  same  region  as  the  centre  for  smell  (in  the  hippocampal  convolu- 
tion posterior  to  the  uncinate  gyrus). 

Ordinary  and  Tactile  Sensations,  including  the  muscular  sense, 
have  been  located  in  the  Rolandic  area  (p.  929) ;  and  there  are  good 
grounds  for  believing  that  afferent  fibres  from  the  joints,  the  muscles 
and  their  accessory  structures  and  the  skin  terminate  here  in  arboriza- 
tions which  come  into  contact  either  \\ith  the  motor  pyramidal 
cells,  or  with  intermediate  cells  which  link  them  to  the  pysamidal 
cells. 

Aphasia. — Words  are,  at  bottom,  arbitrary  signs  by  which  certain 
ideas  arc  expressed.  The  power  of  intelUgent  communication  by  spoken 
or  written  language  may  be  lost:  (i)  by  paralysis  of  the  muscles  of 
articulation  or  the  muscles  which  guide  the  pen;  (2)  by  inability  to 
hear  or  see  the  spoken  or  written  word — i.e.,  bj^  deafness  or  blindness; 
(3)  by  inability  to  comprehend  the  meaning  of  spoken  or  written  lan- 
guage, although  sensations  of  hearing  and  sight  may  not  be  abolished 


FUNCTIONS  OF  THE  BRAIN  933 

— that  is  to  say,  by  inability  to  interpret  the  auditory  or  visual  symbols 
by  which  ideas  are  conveyed;  (4)  by  inability  to  clothe  ideas  in  words, 
although  the  words  may  be  present  in  the  patient's  corusciousness,  and 
the  ideas  conveyed  by  speech  or  writing  may  be  comprehended. 
Neither  (i)  nor  (2)  is  considered  to  constitute  the  condition  of  apliasia; 
(3)  represents  what  is  called  amnesia,  or  sensory  aphasia  ;  (4)  is  aphasia 
in  the  ordinary'  restricted  sense,  or  motor  aphasia. 

Motor  aphasia  may  be  divided  into  two  varieties — subcortical  or  pure 
motor  aphasia,  and  cortical,  or  Broca's  aphasia.  In  tlie  subcortical 
type  the  patient  understands  speech  and  writing  perfectly,  and  is  able 
to  write  normally;  but  he  cannot  speak  spontaneously  or  read  aloud, 
or  repeat  words  when  requested  to  do  so.  He  may  know  quite  well 
what  to  reply  in  answer  to  a  question,  but  the  words  necessary  to 
express  his  meaning  do  not  come  to  him.  In  Broca's  type  of  aphasia, 
which  is  the  most  common,  the  patient  may  understand  spoken 
and  written  words — often  imperfectly,  it  is  true — but  he  is  unable  to 
speak  spontaneously,  to  repeat  words  spoken  to  him,  and  to  read  aloud. 
Unlike  the  person  suffering  from  the  subcortical  type  of  motor  aphasia,  he 
has  difficulty  in  reading  by  the  eye  without  articulation,  and  in  writing 
spontaneously  or  to  dictation.  There  is  often  or  always  some  intellectual 
deficiency.  The  gradations  in  the  loss  of  the  expressive  factor  in  speech 
may  be  infinite.  A  patient  may  sometimes  sing  a  song  without  a  single 
slip  in  words  or  measure,  and  yet  be  unable  to  speak  or  write  it.  In  a 
case  recorded  by  Larionow  an  aphasic  could  speak  only  one  syllable, 
'  tan,'  but  could  sing  the  '  Marseillaise.'  In  certain  cases  the  change 
is  confined  to  loso  of  the  power  of  spontaneous  speech,  and  the  patient 
may  be  able  to  read  intelligently.  Sometimes  he  can  express  his  ideas 
in  speech,  but  not  in  writing  {agraphia) .  Sometimes  the  loss  is  restricted 
to  certain  sets  of  ideas.  For  example,  a  boy  was  injured  by  falling  on 
his  head.  Typical  symptoms  of  motor  aphasia  developed,  but  the 
power  of  dealing  with  ideas  of  number  was  not  interfered  with,  and 
the  boy  continued  to  learn  arithmetic  a^  if  nothing  had  happened. 
Proper  names  and  nouns  are  more  easily  lost  than  adjectives  and  verbs. 
Motor  aphasia  is  generally  accompanied  by  paralysis,  frequently 
transient,  of  voluntary-  movement  on  the  right  side,  sometimes  amount- 
ing to  complete  hemiplegia,  but  more  often  involving  the  right  arm  alone. 
This  association  is  generally  explained  by  the  proximity  cf  the  inferior 
frontal  convolution  to  the  motor  area  of  the  arm,  and  their  common 
blood-supply.  It  has  already  been  stated  that  since  Broca  it  has  been 
generally  assumed  that  in  most  persons  the  inferior  frontal  convolution 
on  the  left  side  is  concerned  in  the  expression  of  ideas  in  spoken  or 
written  language.  It  is  even  said  that  oratorical  powers  have  been 
found  associated  with  marked  development  of  this  convolution  (as  in  the 
case  of  Gambetta,  the  French  statesman).  It  is  the  cortical  or  Broca's 
type  of  motor  aphasia  which  has  been  supposed  to  be  associated  with  a 
lesion  in  the  left  inferior  frontal  convolution.  The  portion  of  the  con- 
volution concerned  is  the  posterior  extremity,  where  it  borders  on  the 
fissure  of  Sylvius,  and  it  either  completely  coincides  with  or  largely 
overlaps  the  centre  for  the  movements  of  the  tongue,  lips,  and  larynx 
concerned  in  articulation.  The  failure,  however,  does  not  lie  in  the 
articulatory  mechanism.  The  patient  uses  the  same  muscles  of  articu- 
lation, without  any  marked  impairment  of  function,  for  chewing  and 
swallowing  his  food.  It  in  only  when  the  corresponding  area  in  the 
right  inferior  frontal  convolution,  or  the  path  from  it  to  the  internal 
capsule,  is  also  destroyed,  that  articulation  is  greatly  and  permanently 
interfered  with. 

The  question  obviously  presents  itself  why  it  is  that  motor  aphasia  is 


936  THE  CENTRAL  NERVOUS  SYSTEM 

commonl}'  due  to  a  lesion  in  the  left  hemisphere  alone.  The  answer  to 
this  question  is  supposed  to  be  partlj-  supplied  by  the  important  and 
curious  observation  that  in  left-handed  individuals  damage  to  the  right 
inferior  frontal  convolution  may  cause  aphasia.  In  the  right-handed 
man  the  motor  areas  of  the  left  hemisphere  may  be  supposed  to  be  more 
highly  ediicated  than  those  of  the  right  hemisphere.  The  movements 
of  the  right  side  which  they  initiate  or  control  are  stronger  and  more 
delicate  and  precise  than  those  of  the  left  side.  It  is  only  necessary  to 
a.ssume  that  this  processs  of  specialization,  of  selective  training,  has 
been  carried  on  to  a  still  greater  extent  in  the  left  frontal  convolution, 
that  in  most  men  the  speech-centre  there  has  taken  upon  itself  the  whole, 
or  the  greater  part,  of  the  labour  of  clothing  ideas  in  words,  leaving  to 
the  right  centre  only  its  primitive  but  undeveloped  powers.  In  left- 
handed  persons  the  speech-centre  on  the  right  side  may  be  supposed  to 
share  in  the  general  functional  development  of  the  right  hemisphere. 
That  great  capabilities  are  lying  dormant  in  the  right  speech-centre  of 
the  ordinary  right-handed  individual  is  indicated  by  the  fact  that  after 
complete  destruction  of  the  left  inferior  frontal  convolution  the  power 
of  speech  may  be  to  a  considerable  extent,  though  slowly  and  laboriously 
regained;  and  it  is  said  that  this  second  accumulation  may  be  swept 
away,  and  without  remedy,  by  a  second  lesion  in  the  right  inferior  frontal 
convolution.  But  frail  is  the  tenure  of  life  in  a  person  who  has  twice 
suffered  from  such  a  lesion ;  and  we  do  not  know  whether  recovery  might 
not  take  place  to  some  extent  even  after  destruction  of  both  inferior 
frontal  convolutions,  if  the  patient  only  lived  long  enough. 

Recently  Marie  has  reopened  the  whole  question  of  the  relation  of 
aphasia  to  lesions  of  the  inferior  frontal  convolution.  He  believes  that 
the  so-caUed  Broca's  area  has  nothing  to  do  with  aphasia  in  the  proper 
sense  of  the  term — i.e.,  it  is  not  a  cortical  area  concerned  in  '  internal ' 
speech  processes,  or  in  which  motor  or  kinaesthetic  '  speech  memories  ' 
are  stored — but  simply  a  '  motor  '  area  for  the  movements  of  articula- 
tion. He  maintains  that  there  is  but  one  form  of  true  aphasia — the 
aphasia  of  Wernicke — which  has  for  its  basis  a  lesion  of  the  so-called 
zone  of  Wernicke  (the  supramarginal  and  angular  gyri,  and  the  posterior 
portions  of  the  first  and  second  temporal  convolutions) .  This,  according 
to  him,  is  the  true  speech-centre.  The  sjinptom-complex  known  as 
Broca's  aphasia,  which  everybody  admits  to  exist  as  a  distinctly  charac- 
terized clinical  condition,  is  due,  he  says,  to  a  double  lesion.  One  lesion 
causes  aphemia  (loss  of  the  power  of  co-ordinating  the  movements 
needed  in  the  articulation  of  words  without  actual  paralysis  of  the 
muscles),  and  the  other  the  disturbance  of  internal  speech,  and  the 
difficulty  of  reading  and  of  writing,  which  constitute  the  true  aphasia. 
According  to  Marie,  the  lesion  which  causes  the  aphemia  is  not  even 
situated  in  Broca's  convolution,  but  somewhere  in  a  rather  badly  de- 
fined region,  which  he  denominates  the  lenticular  zone,  since  it  includes 
the  lenticular  as  well  as  the  caudate  nucleus,  in  addition  to  the  external 
and  internal  capsules  and  the  cortex  of  the  island  of  Reil.  It  would  be 
out  of  place  to  enter  more  minutely  here  upon  such  controversial 
matters.  The  conclusion  which  emerges  most  definitely  from  the  dis- 
cussion is  that  Broca's  localization  was  based  upon  a  very  narrow 
foundation,  and  must  probably  be  modified. 

It  is  generally  recognized  that  in  almost  all  cases  of  aphasia  in  which 
the  brain  has  been  studied  after  death,  some  lesion  of  as.sociation  fibres 
has  been  present,  and  not  merely  a  cortical  lesion.  Interference  with  the 
association  fibres  causes  confusion  in  the  processes  of  association  which 
are  so  important  in  mental  activity,  and  defects  of  intelligence  are  there- 
fore commonly  observed  in  aphasia. 


FUNCTIONS  OF  THE  BRAIN  937 

A  so-called  temporary'  aphasia  may  occur  without  any  structural 
change  in  the  speech-centre — for  example,  during  an  attack  of  migraine. 
In  children  it  may  even  be  caused  by  some  comparatively  slight  irrita- 
tion in  the  digestive  tract,  such  as  that  due  to  the  presence  of  a  tape- 
worm. 

In  the  anthropoid  apes  no  evidence  of  the  existence  of  any  '  speech- 
centre,'  even  distantly  foreshadowing  the  human,  has  been  obtained 
by  stimulating  the  inferior  frontal  convolution  on  either  side.  No  move- 
ments, and  particularly  no  movements  connected  with  vocalization,  are 
elicited. 

Sensory  Aphcisia. — In  typical  motor  aphasia  spoken  and  written 
words  convey  to  the  patient  their  ordinary  meaning.  They  call  up  in 
his  mind  the  usual  sequence  of  ideas,  but  the  chain  is  broken  at  the 
speech-centre,  and  the  outgoing  ideas  cannot  be  clothed  in  words.  The 
expressive  factor  in  speech  is  deranged.  In  sensory  aphasia  the  percep- 
tive factor  in  speech  is  deranged.  In  ordinary  sensory  aphasia  {Wer- 
nicke's, or  cortical  sensory  aphasia)  the  patient  cannot  understand 
spoken  or  written  language,  but,  far  from  being  unable  to  speak,  he 
often  babbles  incessantly.  He  may  string  together  a  series  of  words, 
each  correctly  articulated,  but  having  no  meaning,  or  may  utter  a  jargon 
not  composed  of  known  words  at  all.  Instead  of  the  words  which  he 
desires  to  use  to  express  his  meaning,  he  may  use  others  having  a 
similar  sound  {paraphasia).  Damage  to  two  regions  of  the  brain  has 
been  found  associated  with  this  condition:  (i)  the  middle  part  of  the 
first  and  second  temporal  convolutions,  (2)  inferior  parietal  convolu- 
tions and  the  angular  g>^rus  in  the  neighbourhood  of  the  occipital  visual 
centre.  When  the  temporal  region  is  alone  affected,  it  is  the  spoken 
word  that  is  missed,  the  written  that  is  understood  {word-deafness). 
WTien,  as  occasionally  happens,  the  lesion  is  confined  to  the  occipital 
region,  spoken  language  is  perfectly  understood,  written  language  not 
at  all  {word-blindness).  It  is  the  left  hemisphere  wh-ch  is  affected  in 
right-handed  persons,  the  right  hemisphere  in  left-handed  persons. 
Sensory,  like  motor  aphasia,  may  exist  in  any  degree  of  completeness, 
from  absolute  word-deafness  or  word-blindness,  in  which  no  spoken  or 
printed  word  calls  up  any  mental  image,  to  a  condition  not  amounting 
to  much  more  than  a  marked  absence  of  mind  or  unusual  obtuseness. 
Motor  and  sensory  aphasia  may  be  present  together.  In  well-marked 
cortical  word-deafness  speech  is  always  interfered  with  to  some  extent. 
In  so-called  pure  word-deafness  (subcortical  sensory-  aphasia)  the  patient 
may  be  perfectly  capable  of  rational  speech.  He  may  talk  to  himself 
or  on  a  set  topic  with  fluency  and  sense,  may  write  intelligently,  and 
understand  what  he  reads ;  but  he  may  be  unable  to  understand  a  single 
word  spoken  to  him,  or  to  repeat  words  when  asked  to  do  so. 

Cortical  Epilepsy. — Disturbed  action  of  the  motor  centres  may  take 
the  form  either  of  depression  or  of  increased  excitability.  The  former 
will  be  associated  with  partial  or  complete  paralysis  of  the  movements 
represented  in  the  area,  the  latter  by  abnormally  intense  or  prolonged 
discharge  leading  to  the  condition  called  cortical  epilepsy — tliat  is, 
epileptic  attacks  associated  with  cortical  lesions.  Among  these  are  the 
cases  of  so-called  Jacksonian  epilepsy — a  condition  characterized  by  the 
fact  that  the  seizure  does  not  begin  by  general,  but  by  local,  convulsions. 
They  ma.y  remain  confined  to  a  single  limb,  or  to  one  side  of  the  face,  or 
to  one  side  of  the  body.  So  long  as  the  convulsions  are  not  general, 
consciousness  need  not  be  lost.  Or  a  seizure  beginning  as  Jacksonian 
may  spread  so  as  to  involve  the  whole  todv,  in  which  case  the  symptoms 
become  identical  with  those  of  ordinan,-  cp«lcp.<;y,  including  the  loss  of 
consciousness.     It  has  been  found  possible  in  some  cases  to  localize  the 


938  THE  CENTRAL  NERVOUS  SYSTEM 

position  of  the  lesion  from  the  pait  of  the  body  in  which  the  fit,  or  the 
aura  (the  sensation  or  group  of  sensations  pecvihar  to  each  case,  which 
precedes  and  announces  the  attack)  begins.  For  example,  if  the  con- 
vulsions commence  with  a  twitching  of  the  right  thumb  and  extend  over 
the  arm,  or  if  the  aura  consists  of  sensations  beginning  in  the  thumb, 
there  is  a  strong  presumption  that  the  seat  of  the  lesion  is  the  part  of  the 
arm-area  known  as  the  '  thumb-centre  '  in  the  left  cerebral  hemisphere. 
It  is  the  seat  of  the  convulsion  at  its  commencement,  not  the  regions  to 
which  it  may  afterwards  spread,  that  is  important  in  diagnosing  the 
position  of  the  lesion.  For  just  as  strong  or  long-continued  electrical 
stimulation  of  a  given  '  centre  '  of  the  '  motor  '  cortex  may  give  rise  to 
contractions  of  muscles  associated  with  other  '  centres,'  so  the  excita- 
tion set  up  by  localized  disease  may  spread  far  and  wide  from  its 
original  focus,  involving  area  after  area  of  the  '  motor '  region  first  in 
the  one  hemisphere  and  then  in  the  other.  The  part  of  the  body  to 
which  a  sensory  aura  is  referred  is  as  significant  an  indication  of  the 
seat  of  the  discharging  lesion  as  is  the  part  of  the  body  which  first  begins 
to  twitch.  This  is  one  of  the  proofs  that  the  '  motor  '  region  is  not  a 
purely  motor  area.  Disturbed  action  of  the  sensory  areas  on  the  cortex 
may,  as  in  the  case  of  the  motor  regions,,  take  the  form  either  of  de- 
ficiency or  of  excitation.  Excitation  expresses  itself  by  hallucinations, 
the  person  having  the  impression  of  a  sight,  a  sound,  a  smell  or  taste,  or 
one  or  other  of  the  cutaneous  sensations  in  the  absence  of  the  rehied 
objects. 

Seat  of  Intellectual  Processes — ^Association  Areas. — When  we 
have  deducted  from  the  cortex  of  the  hemisphere  the  whole  Rolandic 
region  and  the  sensory  centres,  there  still  remains  a  large  territory 
unaccounted  for.  Considerable  portions  of  the  occipital,  parietal, 
and  temporal  lobes,  nearly  the  whole  of  the  island  of  Reil  and  the 
greater  part  of  the  frontal  lobe  anterior  to  the  ascending  frontal 
convolution  are  '  silent  areas,'  and  respond  to  stimulation  by  neither 
motor  nor  sensory  sign.  They  correspond  to  the  association 
centres  previously  referred  to.  They  are  connected  with  the 
sensory  and  motor  areas  and  with  each  other,  but  are  not  directly 
connected  by  projection  fibres  with  the  lower  parts  of  the  central 
nervous  system,  as  the  motor  area,  for  example,  is  by  the  pyramidal 
path.  By  a  process  of  exclusion  it  has  been  supposed  that,  in  addi- 
tion to,  or  partly  in  virtue  of,  their  associative  function,  they  are 
the  seat  of  intellectual  and  psychical  operations.  It  is  supposed 
that  the  sensations  aroused  in  the  various  sensory  areas  by  the 
impulses  received  from  the  sense  organs  are  linked  in  the  associa- 
tion areas  into  complex  perceptions.  For  instance,  when  an 
orange  is  taken  into  the  hand,  the  visual  sensation  of  a  yellow  body, 
the  tactile  sensation  of  a  smooth  round  body,  and  perhaps  the- 
olfactory  sensation  characteristic  of  an  orange,  are  collected  from 
the  sensory  areas,  connected  and  combined,  or  synthesized  in  an 
association  area  to  the  concept  of  an  orange.  Somewhere  in  the 
association  areas  it  is  to  be  supposed  is  stored  the  memory  of  past 
experiences.  The  intellectual  function  has  been  more  particularly 
assigned  to  the  frontal  lobes,  and  with  great  probability,  although 


FUNCTIONS  OF  THE  BRAIN  939 

we  have  little  real  knowledge  to  guide  us  to  a  decision.  Extensive 
destruction  and  loss  of  substance  of  the  prefrontal  region  may 
sometimes  occur  without  any  marked  symptoms.  But  usually 
there  is  restriction  of  mental  power,  or  it  may  be  loss  of  moral 
restraint.  Thus  in  the  famous  '  American  crowbar  case,'  an  iron 
bar  completely  transfixed  the  left  frontal  lobe  of  a  man  engaged 
in  blasting.  Although  stunned  for  the  moment,  he  was  ai)le  in 
an  hour  to  climb  a  long  flight  of  stairs,  and  to  answer  the  inquiries 
of  the  surgeon.  Finally,  he  recovered,  and  lived  for  nearly  thirteen 
years  without  either  sensory  or  motor  deficiency,  except  that  he 
suffered  occasionally  from  epileptic  convulsions.  But  his  intellect 
was  impaired;  he  became  fitful  and  vacillating,  profane  in  his 
language  and  inefficient  in  his  work,  although  previously  decent  in 
conversation  and  a  diligent  and  capable  workman. 

Flechsig  supposes  that  his  great  anterior  association  centre  in  the 
frontal  lobe  is  concerned  in  the  retention  of  the  mtmory  of  all  conscious 
bodily  experiences,  especially  those  connected  with  voluntary  acts. 
The  great  posterior  association  centre  he  imagines  to  be  engaged  in  the 
formation  and  collection  of  ideas  of  external  objects  and  of  the  '  word 
pictures  '  which  represent  them,  and  with  the  preparation  of  speech  in 
respect  of  the  thoughts  to  be  expressed  and  the  form  of  expression,  the 
office  of  the  Broca's  area  (but  see  p.  936)  being  to  execute  the  mechanical 
part  of  the  process  by  transforming  these  thoughts  into  actual  spoken 
words.  This  posterior  association  centre  may  be  looked  upon  as  the 
seat  of  intellect  in  the  narrower  sense,  as  the  anterior  is  of  will  and  feeling. 

The  experiments  of  Franz  on  the  relation  of  the  cerebral  association 
areas,  and  especially  the  frontal  area,  to  certain  acquired  habits  are  of 
interest.  Cats  were  allowed  to  acquire  certain  habits  involving  simple 
mental  processes,  and  then  it  was  seen  how  these  were  affected  by 
cortical  lesions.  After  bilateral  extirpation  of  the  frontal  lobes  (the 
area  anterior  to  the  crucial  sulcus)  newly -formed,  but  not  long-standing, 
habits  are  lost.  This  cannot  be  due  to  shock,  since  other  brain  lesions 
are  not  follow^ed  by  loss  of  the  habits.  Extirpation  of  one  frontal  area 
usually  causes  a  partial  loss  of  newly-acquired  habits,  or,  rather,  a  slow- 
ing of  the  association  process  leading  to  unusual  delay  in  the  execution 
of  the  movements  connected  with  the  habit.  Habits  once  lost  after 
removal  of  the  frontal  lobes  may  be  relearned. 

The  influence  of  psychical  events  upon  bodily  functions  is  well  known, 
and  has  been  more  than  once  illustrated  in  preceding  pages.  The  con- 
verse question  of  the  influence  of  bodily  states  upon  psychical  events 
has  also  been  raised,  especially  in  connection  with  the  genesis  of  emotion. 
Some  psychologists  assume  that  the  bodily  changes  associated  with  sueli 
emotions  as  grief,  fear,  rage,  or  love,  are  not  evoked  as  a  consequence  of 
the  emotions,  but  that  the  bodily  changes  follow  directly  the  perception 
of  the  exciting  fact — e.g.,  a  spectacle  which  causes  fear  or  rage,  '  and 
that  our  feeling  of  the  same  changes  as  they  occur  is  the  emotion  ' 
(James).  Sherrington,  however,  has  shown  that  in  dogs  in  which,  by 
transection  of  the  vagi  and  the  spinal  cord,  all  sensation  of  viscera,  skin, 
and  muscles  behind  the  level  of  the  shoulder  was  eliminated,  no  obvious 
emotional  defect  was  caused.  Notwithstanding  the  immense  abridg- 
ment of  the  field  of  sensation,  anger,  jov,  fear,  disgust  (as  on  being 
offered  dog's  flesh,  which  most  dogs  refuse  to  cat),  were  as  marked  as 
ever,  and  were  evoked  by  the  same  objects  as  before  the  o^xTation 


940  THE  CENTRAL  NERVOUS  SYSTEM 

When  the  afferent  field  is  stiU  more  restricted,  as  in  the  head  of  a  dog 
grafted  on  the  circulation  of  another  dog  by  anastomosis  of  the  blood- 
vessels, with  precautions  to  avoid  interruption  of  the  blood-flow,  not 
only  does  the  respiratory  centre  continue  to  discharge  itself  with  a 
regular  rhythm,  but  cortical  volitional  movements  persist  (Guthrie, 
Pike,  and  Stewart),  and,  so  far  as  can  be  judged,  sense  perception, 
emotional,  and  even  intellectual,  processes  continue.  In  one  case  the 
picture  presented  by  the  engrafted  head  was  essentially  the  same  as  that 
presented  by  the  head  of  the  '  host '  for  over  two  hours.  In  a  trans- 
planted head  from  a  younger  dog  in  which  the  circulation  had  been 
interrupted  for  twenty-nine  minutes,  a  remarkable  return  of  cerebral 
function  was  observed  (Guthrie). 

Localization  of  Function  in  the  Central  Nervous  System. — Let 
us  now  consider  a  little  more  closely  the  real  meaning  of  this 
localization  of  function.  Scattered  all  over  the  grey  matter  oi 
the  primitive  neural  axis,  and,  as  we  have  seen,  over  the  grey  mantle 
of  the  brain  as  well,  are  numerous  '  centres  '  which  seem  to  be 
related  in  a  special  way  to  special  mechanisms,  sensory,  secretory, 
or  motor.  The  question  may  fitly  be  asked  whether  those  centres 
are  really  distinct  from  each  other  in  quality  of  structure  or  action, 
or  whether  they  owe  their  peculiar  properties  solely  to  differences 
in  situation  and  anatomical  connection.  It  is  clear  at  the  outset 
that  the  nature  of  the  work  in  which  a  centre  is  engaged  must  be 
largely  determined  by  its  connections.  The  kind  of  activity  which 
goes  on  in  the  vaso-motor  centre  in  the  bulb,  for  example,  may 
in  no  essential  respect  differ  from  that  which  goes  on  in  the  respira- 
tory centre.  The  calibre  of  the  bloodvessels  will  alter  in  response 
to  a  change  of  activity  in  the  one  because  it  is  anatomically  con- 
nected with  the  muscular  coat  of  the  bloodvessels.  The  rate  or 
depth  of  the  respiratory  movements  will  alter  in  response  to  a 
change  of  activity  in  the  other,  because  it  is  connected  with  muscles 
which  can  act  upon  the  chest-walls. 

Experiments  on  the  anastomosis  of  nerves  afford  a  very  interesting 
illustration  of  the  determining  influence  of  their  peripheral  con- 
nections on  the  function  of  nerve-fibres.  It  has,  in  fact,  been 
shown  that  the  central  end  of  any  efferent  somatic  fibre— f.g.,  any 
fibre  running  from  the  central  nervous  system  and  ending  in 
striated  muscle — can  make  functional  connection  with  the  periph- 
eral end  of  any  other  efferent  fibre  of  the  same  class,  whatever  be 
the  normal  actions  produced  by  the  two  fibres.  Advantage  has 
been  taken  of  this  in  surgery.  For  instance,  in  a  case  of  severe 
facial  (motor)  tic  the  facial  nerve  was  divided,  and  its  peripheral 
end  united  with  a  portion  of  the  fibres  of  the  spinal  accessory.  The 
voluntary  movements  of  the  face,  after  regeneration  had  occurred, 
were  normally  carried  out  through  impulses  descending  the  spinal 
accessory.  In  cases  of  local  paralysis,  due  to  destruction  of  anterior 
horn-cells  (anterior  poliomyelitis),  restoration  of  movement  has 
also  been  obtained  by  connecting  the  motor  nerve  of  the  paralyzed 


FUNCTIONS  OF  THE  BRAIN  94I 

muscles  to  a  portion  of  a  nerve  coming  off  from  an  uninjured  region 
of  tlie  cord. 

By  such  operations  it  has  been  possible  to  transpose  motor  areas 
on  the  cerebral  cortex  associated  with  the  flexion  and  extension 
of  a  particular  joint,  so  that  the  part  of  the  cortex  which  originally 
caused  flexion  after  the  nerve  anastomosis  causes  extension,  and 
vice  versa.  When  the  nerves  supplying  a  group  of  muscles  of  the 
dog's  fore-limb  are  eliminated,  the  nerves  of  the  antagonistic  group 
may  be  used  to  supply  both  groups,  and  co-ordinated  movements 
may  be  restored,  although  this  does  not  occur  so  rapidly  as  when 
the  nerves  supplying  the  two  groups  are  simply  cut  and  cross- 
sutured  (Kennedy).  However,  the  limitati£)ns  of  this  method 
ought  to  be  recognized.  Before  any  anastomosis  of  nerves  can  be 
made,  good  fibres  must  first  be  destroyed.  Under  favourable  cir- 
cumstances these  may  all  regenerate  and  find  their  way  to  the  struc- 
tures they  are  intended  to  innervate.  When  regeneration  is  com- 
plete, the  number  of  fibres  capable  of  functioning  will  at  best  be  the 
same  as  before  the  operation,  and  may  easily  be  considerably  less. 
The  benefit,  whatever  it  is,  will  be  associated  solely  with  the  re- 
distribution of  the  fibres.  There  is  reason  to  think  that  the  closer 
to  the  cell  of  origin  a  nerve  is  injured  or  divided,  the  less  is  the  chance 
of  restoration,  and  Feiss  has  found  that  after  lesions  in  the  cord 
or  the  spinal  roots  neither  the  anatomical  pattern  of  the  affected 
nerves  nor  their  functional  power  is  much  affected  by  subsequent 
nerve  anastomosis. 

The  central  end  of  any  efferent  somatic  fibre  can  also  make 
functional  union  with  the  peripheral  end  of  any  of  the  efferent  fibres 
which  run  from  the  central  nervous  system  and  end  in  ganglion 
cells  (pre-gangHonic  fibres),  and  the  central  end  of  any  pre-gan- 
glionic  fibre  can  do  the  same  with  the  peripheral  end  of  any  efferent 
somatic  fibre  (Langley  and  Anderson).  For  instance,  Langley 
divided  (in  cats)  the  vagus  nerve  and  the  cervical  sympathetic. 
The  peripheral  end  of  the  former  degenerated,  of  course,  below  the 
section,  and  the  peripheral  (cephalic)  end  of  the  latter  degenerated 
above  the  section,  up  to  the  terminations  of  its  axons  in  the 
superior  cervical  ganglion.  The  central  end  of  the  cut  vagus  was 
subsequently  sutured  to  the  peripheral  end  of  the  cut  sympathetic. 
After  a  time  the  vagus-fibres  grew  along  the  course  of  the  degener- 
ated sympathetic  up  to  the  ganglion,  where  some  of  them  formed 
arborizations  around  the  ganglion  cells.  It  was  now  found  that 
stimulation  of  the  vagus  produced  the  effects  usually  caused  by 
stimulation  of  the  cervical  sympathetic — for  example,  dilatation 
of  the  pupil  and  constriction  of  the  bloodvessels  of  the  head  and 
neck.  From  these  experiments  it  follows  that  the  functions  of  the 
various  groups  of  fibres  in  the  cervical  sympathetic  do  not  depend 
on  anything  peculiar  to  the  fibres;  any  fibre  which  can  make  con- 


942  THE  CENTRAL  NERVOUS  SYSTEM 

nection  with  one  of  the  ganglion  cells  that  send  axons  to  the 
dilator  muscle  of  the  iris  will,  when  stimulated,  act  as  a  pupillo- 
dilator  fibre,  just  as  well  as  a  cervical  sympathetic  fibre.  Other 
instances  of  the  same  law  have  already  been  given  in  connection 
with  the  regeneration  of  nerves  (p.  774). 

Functional  union  does  not  take  place  between  efferent  somatic 
fibres  (or  pre -ganglionic  fibres)  and  post-ganglionic  fibres — i.e., 
fibres  arising  in  peripheral  ganglia,  and  ending  in  smooth  muscle 
and  glandular  tissue;  e.g.,  the  cervical  sympathetic  after  excision 
of  the  superior  cervical  ganglion  does  not  unite  with  the  fibres 
leaving  the  anterior  end  of  the  ganglion  in  such  a  way  that  stimula- 
tion of  it  can  produce  any  of  the  effects  normally  produced  through 
these  fibres.  No  proof  has  been  given  that  afferent  fibres  can  unite 
with  efferent  fibres  or  efferent  with  afferent. 

Afferent  fibres  of  one  nerve  can  unite  with  afferent  fibres  of 
another  nerve,  but  there  is  not  sufficient  evidence  to  show  whether 
fibres  concerned  in  one  sensation  can  unite  with  fibres  concerned 
in  another. 

The  localization  of  function  in  the  cerebral  cortex  has  been  likened  to 
the  localization  of  industries  in  the  multiplex  commercial  life  of  the 
modem  world.  The  barbarian  household  in  which  cloth  is  woven  and 
worked  into  garments;  sandals,  or  moccasins  cobbled  together;  rough 
pottery  baked  in  the  kitchen  fire,  and  all  the  rude  furniture  of  the  lodge 
fashioned  by  the  hands  which  built  it,  and  which  rest  beneath  its  roof  at 
night — this  state  of  things  where  centralization  has  not  yet  begun,  it 
has  been  said,  is  a  picture  of  what  goes  on  in  the  undeveloped  brains  of 
the  frog,  the  pigeon,  and  the  rabbit.  The  '  diffusion  '  of  industries 
which  is  characteristic  of  a  primitive  state  has  given  place  among  the 
most  highly  civilized  men  to  extreme  centralization  and  concentra- 
tion. Manchester  spins  cotton  and  Liverpool  ships  it.  Chicago  handles 
wheat  and  pork  that  have  been  produced  on  the  prairies  of  Minnesota 
and  Illinois.  Amsterdam  cuts  diamonds.  Munich  brews  beer.  Lyons 
weaves  silk.  New  York  and  London  are  centres  of  finance.  This,  it  is 
said,  is  the  picture  of  the  highly  specialized  brain  of  a  monkey  or  a  man. 
But  ingenious  and  alluring  though  such  analogies  are,  they  do  not  rest 
upon  a  sufficient  basis  of  fact.  Indeed,  the  more  deeply  the  structure 
and  function  of  the  central  nervous  system  are  studied,  the  more  clearly 
does  its  essential  solidarity  appear,  the  more  clearly  does  it  emerge  as  an 
organized  co-ordinated  system,  not  an  aggregate  of  separate  mechanisms 
jumbled  together  for  convenience  of  storage  in  the  protected  cranio- 
spinal cavity. 

It  has  never  been  shown — nor  is  it  likely  that  the  proof  will  soon  be 
forthcoming — that  there  is  any  difference  whatever  in  the  physical, 
chemical,  or  psychical  processes  which  go  on  in  the  various  centres  of 
the  '  motor '  cortex.  It  may  be  supposed,  indeed,  that  the  so-called 
sensory  areas  of  the  cortex  differ  more  widely  in  theip  internal  activity 
from  the  '  motor  '  areas  than  the  latter* do  among  themselves,  and  that 
the  activity  of  the  anterior  portion  of  the  brain,  the  portion  which  has 
been  credited  par  excellence  with  pyschical  functions,  differs  in  kind,  not 
merely  in  degree,  from  that  of  all  the  rest.  But,  as  we  have  just  seen, 
even  the  '  motor  '  areas  have  sensory  functions.  A  cast-iron  physiology 
may  explain  this  by  the  assumption  of  '  sensory  '  as  well  as  '  motor ' 
cells  in  the  Rolandic  area,  and  may  find  support  for  such  an  assumption 


FUNCTIONS  OF  THE  BRAIN  943 

in  the  well-knouTi  fact  that  the  large  pyramidal  cells  whose  axons  form 
the  pyramidal  tract  make  up  but  a  small  pro{X)rtion  of  the  total  number 
of  pyramidal  cells  in  this  region,  which,  besides,  contains  numerous  cells 
of  Golgi's  second  type  (p.  828).  And  although  it  may  be  true  that  the 
tactile  sensations  constituting  the  so-called  body-sense  are  represented 
mainly  not  in  the  motor  region  itself,  but  in  the  adjacent  gyTUS  post- 
centralis  posterior,  to  the  Rolandic  fissure  (p.  918],  there  is  nothing  to 
contradict  the  supposition  that  the  discliarge  of  energy  from  the  most 
circumscribed  motor  area  or  element  may  be  accompanied  with  con- 
sciousness. And,  indeed,  some  writers  have  supposed  that  such  a 
consciousness  of,  or  even  conscious  measurement  of,  the  discharge 
from  the  '  motor '  areas  is  the  basis  of  the  muscular  sense  (Bain, 
Wundt). 

So  far,  at  least,  as  the  '  motor  '  region  and  the  grey  matter  imme- 
diately around  the  neural  canal  are  concerned,  the  analog^'  of  an 
electrical  switch-board  connected  with  machines  of  various  kinds  might 
be  more  correct.  Touch  one  key  or  another,  and  an  engine  is  set  in 
motion  to  grind  com,  or  to  saw  wood,  or  to  light  a  town.  The  difference 
in  result  lies  not  in  any  difference  of  material  or  workmanship  in  the 
switches,  but  solely  in  the  difference  in  their  connections. 

Grey  matter  in  the  upper  part  of  the  precentral  convolution  is  excited, 
and  the  muscles  of  the  leg  contract.  Grey  matter  on  the  lower  part  of 
the  convolution  is  excited,  and  there  are  movements  of  the  face  and 
mouth.  Grey  matter  in  the  medulla  oblongata  is  excited,  and  the 
sjilivary  glands  pour  forth  a  thin,  watery  fluid,  poor  in  proteins,  and 
containing  an  amylol}-tic  ferment.  Another  portion  of  grey  (?)  matter 
In  the  medulla  is  thrown  into  activity,  and  the  pancreatic  ducts 
become  flushed  with  a  thicker  secretion,  relatively  rich  in  proteins  and  in 
ferments  which  act  on  proteins,  starch,  and  fat.  Here,  too,  there  is  a 
variety  in  result  according  as  one  or  another  ner\-ous  switch  is  closed ; 
here,  too,  the  variety  is  due,  not  to  essential  differences  in  the  structure 
of  the  activity  or  the  ner\'Ous  centres,  but  to  their  connection,  by  ner\ous 
paths,  with  peripheral  organs  of  different  kinds.  There  is,  indeed,  a 
specialization,  a  localization,  of  function,  but  the  localization  is  at  the 
periphery,  the  specialization  is  in  the  peripheral  organs. 

It  may  be  asked  whether,  if  this  is  the  case  for  the  peripheral  organs 
of  efferent  nerves,  the  converse  does  not  hold  true  for  the  afferent  nerves 
— in  other  words,  whether  the  localization  here  is  not  at  the  centre.  And 
that  there  is  in  some  degree  a  central  locahzation  of  sensation  may  be 
considered  proved  by  the  well-known  clinical  fact,  already  referred  to, 
that  sensations  of  various  kinds  may  be  produced  by  pathological 
changes  in  the  cortex.  For  example,  a  tumour  involving  the  upper  part 
of  the  temporal  lobe  may  give  rise  to  epileptiform  convulsions  preceded 
by  an  auditory  aura,  a  sound,  it  may  be,  resembling  the  ringing  of  bells ; 
a  tumour  involving  the  occipital  region  may  cause  a  visual  aura,  ai:d  so 
on.  Central  sensory  localization  is  the  fundamental  idea  of  the  old 
doctrine  of  the  specific  energy  of  nerves,  which,  in  modem  phraseology', 
expresses  the  fact  that  excitation  of  the  central  end  of  a  sensor\'  nerve 
by  various  kinds  of  stimuli  causes  always — or  at  least  very  often — the 
particular  kind  of  sensation  appropriate  to  the  nerve.  The  observ-ation 
so  frequently  made  in  surgery  before  the  days  of  anicsthetics,  that  when 
the  optic  nerve  was  cut  in  removing  the  eyeball  the  patient  experienced 
the  sensation  of  a  flash  of  light,*  was  long  looked  ujx)n  as  the  strongest 
prop  of  the  law  of  specfic  energy,  and  well  illustrates  the  meaning  of  the 
term.  Here  a  mechanical  excitation  of  the  optic  fibres  in  their  course 
gives  rise  to  tlie  same  sensation  as  excitation  of  the  retina  by  the 

*  It  is  said  that  this  is  not  always  the  case. 


944  THE  CENTRAL  NERVOUS  SYSTEM 

natural  or  homologous  or  adequate  stimulus  of  light.  Since  a  similar 
mechanical  stimulus  applied  to  the  auditory  nerve  gives  rise  to  a  sensa- 
tion of  sound,  and,  applied  to  the  trigeminal  nerve,  to  a  sensation  of  pain, 
many  physiologists  have  assumed  that  the  impulses  set  up  in  the 
auditorj^  nerve  when  sound  impinges  on  the  tympanic  membrane  do  not 
differ  essentially  from  those  set  up  in  the  optic  ner^•e  when  a  ray  of  light 
falls  upon  the  retina,  or  from  those  set  up  in  the  fifth  ner\^e  by  the  irri- 
tation of  a  carious  tooth,  or  from  those  set  up  in  certain  fibres  of  the 
cutaneous  nerves  when  a  warm  body  comes  in  contact  with  the  skin. 
Since  the  results  in  consciousness  are  very  different,  this  assumption  has 
necessitated  the  further  conclusion  that  somewhere  or  other  in  the 
central  nervous  system  there  exist  organs  that  are  dift'erently  affected 
by  the  same  kinds  of  afferent  impulses — in  other  words,  that  sensory 
localization  is  at  the  centre.  On  this  view,  the  viscual  areas  in  the  cortex 
respond  to  all  kinds  of  stimuli  by  visual  sensations ;  the  auditory  areas 
by  sensations  of  sound,  and  so  on. 

But  while  it  cannot  be  doubted  that  special  sensory  regions  exist  in. 
the  grey  matter  of  the  brain,  where  the  afferent  paths  concerned  in  the 
different  kinds  of  sensation  end,  it  has  not  been  proved  that  the  nerve- 
impulses  wliich  travel  up  the  various  paths  are  absolutely  similar  until 
they  have  reached  the  centres,  and  there  suddenly  become,  or  produce, 
sensations  absolutely  different.  There  is,  indeed,  evidence  of  a  certain 
amount  of  sensory  specialization  at  the  periphery.  For  example,  when 
an  ordinary'  nerve-trunk  is  touched,  the  resultant  sensation  is  not  one 
of  touch.  If  there  is  any  sensation  at  all,  it  is  one  of  pain.  Heating 
or  cooling  a  naked  nerve-trunk  gives  rise  to  no  sensations  of  tempera- 
ture. When  the  ulnar  nerve  is  artificially  cooled  at  the  elbow,  the  first 
effect  is  severe  pain  in  the  parts  of  the  hand  supplied  by  the  nerve.  The 
pain  disappears  somewhat  abruptly  as  cooling  goes  on,  and  is  succeeded 
by  gradual  loss  of  all  sensation  in  the  ulnar  area  of  the  hand ;  but  the 
cooling  of  the  nerve-trunk  does  not  give  rise  to  any  sensation  of  cold 
(Weir  Mitchell) .  Stimulation  of  the  receptors  or  end -organs  is  normally 
essential  in  order  that  sensations  of  touch  and  temperature  should  be 
experienced.  Although  as  previously  stated,  one  great  function  of 
the  receptor  is  to  lower  the  threshold  of  the  adequate  stimulus, 
and  thus  to  render  the  afferent  neuron  more  easily  excited  by  an 
adequate  stimulus  than  by  any  other,  it  may  also  serve  to  impress  a 
particular  rhythm  or  other  character  upon  the  nerve  impulse,  so  that  the 
afferent  impulses  may  be  to  some  extent  differentiated  before  they  reach 
their  centres.  One  reason,  then,  why  excitation  of  the  temporal  cortex 
by  impulses  falling  into  it  along  the  auditor^'-  nerve-fibres  causes  a  sensa- 
tion different  from  that  caused  by  impulses  reaching  the  occipital  cortex 
through  the  fibres  of  the  optic  nerve  may  be  a  difference  in  the  nature  of 
the  impulses.  If  this  were  the  only  reason,  it  would  follow  that  were  it 
possible  to  physiologically  connect  the  fibres  of  the  optic  radiation  with 
the  temporal  cortex,  and  those  of  the  temporal  radiation  with  the 
occipital  cortex,  sights  and  sounds  would  still  be  perceived  and  dis- 
criminated in  a  normal  manner,  although  now  the  integrity  of  the 
occipital  lobe  would  be  bound  up  with  the  perception  of  sound,  the 
integrity  of  the  temporal  lobe  with  visual  sensation.  This  state  of 
affairs  would  correspond  to  complete  specialization  for  sensation  in  the 
peripheral  organs,  complete  absence  of  specialization  in  the  centres.  On 
the  other  hand,  it  is  conceivable  that,  after  such  an  ideal  experiment, 
sound-waves  falling  on  the  auditory  apparatus  might  cause  visual 
sensations,  and  luminous  impressions  falling  on  the  retina  sensations  of 
sound.  This  would  correspond  to  complete  specialization  of  sensation 
in  the  centres,  complete  absence  of  specialization  at  the  periphery.     A 


FUNCTIONS  OF  THE  BRAIN  945 

third  possibility  would  be  that  the  '  transposed  '  centres,  responding  at 
first  feebly  or  not  at  all  to  the  new  impulses,  might,  by  slow  degrees, 
become  more  and  more  excitable  to  them.  This  would  correspond  to  a 
peripheral  specialization,  combined  with  a  tendency  to  development  of 
central  specialization.  And,  indeed,  it  is  not  easy  to  conceive  in  what 
way,  except  as  the  result  of  differences  in  the  nature  of  impulses  coming 
from  the  periphery,  specialization  of  sensory  areas  in  the  central  nervous 
system  could  have  at  first  arisen. 

Degree  of  Localisation  in  Different  Animals. — Before  leaving  this 
subject,  two  points  ouL^ht  to  he  made  clear:  (i)  The  degree  of 
localization  of  function  in  the  cortex  goes  hand  in  hand  with  the 
general  development  of  the  brain.  In  man  and  the  monkey,  the 
motor  localization  is  more  elaborate  than  in  the  dog — that  is  to 
say,  a  greater  number  of  movements  can  be  associated  with  definite 
cortical  areas.  In  the  rabbit,  whose  '  motor  '  centres  have  been 
particularly  studied  in  recent  years  by  Mann  and  Mills,  localization 
is  still  less  advanced  than  in  the  dog.  Towards  the  bottom  of  the 
mammalian  group  certain  '  motor  '  areas  can  still  be  demonstrated, 
though  they  are  rather  ill-defined,  for  instance  in  the  hedgehog 
(Mann),  opossum  (Cunningham),  and  omithorhynchus  (Martin). 
In  general  the  movements  of  the  anterior  limb  are  easier  to  obtain 
than  those  of  the  posterior.  In  birds  Mills  found  no  evidence  of  the 
existence  of  any  '  motor  '  centres. 

(2)  Areas  of  the  same  name  (homologous  areas)  in  different  groups 
of  animals  do  not  necessarily  have  the  same  function — that  is,  in 
the  case  of  the  '  motor  '  areas,  are  not  necessarily  associated  with 
the  same  movements.  Taking  the  position  of  the  centre  for  the 
orbicularis  oculi  as  a  test,  Ziehen  has  come  to  the  conclusion  that 
in  the  anthropoid  apes  and  in  man  this  centre  has  been  pushed 
forward  by  the  encroachment  of  the  centres  behind  it,  and  especially 
of  the  visual  centre,  the  arm  centre,  and  the  speech  centre,  which 
have  undergone  a  great  functional  development. 

Acquisition  of  Co-ordination  of  Voluntary  Movements. — The  co-ordina- 
tion of  movements  has  already  been  alluded  to  in  connection  with  the 
spinal  reflexes.  No  fundamental  distinction  can  be  drawn  between  the 
co-ordination  of  reflex  and  of  voluntary  movements,  but  the  conscious 
and  often  long-continued  efforts  necessary  to  acquire  master^'  over  the 
latter  lends  to  their  co-ordination  a  special  interest.  The  new-bom  child 
brings  with  it  into  the  world  a  certain  endowment  of  co-ordinative 
powers;  it  has  inherited,  for  example,  from  a  long  line  of  mammalian 
ancestors  the  power  of  performing  those  movements  of  the  cheeks,  lips, 
and  tongue,  on  which  sucking  depends;  perhaps  from  a  long,  though 
somewhat  shadowy,  race  of  arboreal  ancestors  the  power  of  clinging 
with  hands  and  feet,  and  thus  suspending  itself  in  the  air.  Many  move- 
ments, such  as  walking  and  the  co-ordinated  muscular  contractions 
involved  in  standing,  and  even  in  sitting,  which,  once  acquired,  appear 
so  natural  and  spontaneous,  have  to  be  learnt  by  painful  effort  in  the 
hard  school  of  (infantile)  experience,  and  this  despite  the  fact  that  in 
these  movements  the  voluntary  co-ordination  mechanism  makes  use  to 

60 


946  THE  CENTRAL  NERVOUS  SYSTEM 

a  great  extent  of  a  motor  machinery  already  existing  in  the  cord  and 
capable  of  discharging  well  co-ordinated  reflexes.  In  addition  to  such 
fundamental  movements,  most  people  consciously  learn,  and  are 
willing  to  confess  that  they  have  learnt,  to  execute  a  considerable 
number  of  co-ordinated  movements  with  the  arms,  and  especially  with 
the  fingers.  Some  part  even  of  the  extreme  dexterity  of  jaws,  tongue, 
and  teeth  displayed  by  a  hungry  school-boy,  in  a  minor  degree,  perhaps, 
by  a  hungry  mouse,  is  the  result  of  the  much  practice,  entailing  at  first 
some  conscious  effort,  which  maketh  perfect.  The  exquisite  co-ordina- 
tion of  the  muscles  of  the  eyeball,  which  we  shall  afterwards  have  to 
speak  of,  and  the  no  less  wonderful  balance  of  effort  and  resistance,  of 
power  put  forth  and  work  to  be  done,  of  which  we  have  already  had 
glimpses  in  studying  the  mechanism  of  voice  and  speech,  become  to  a 
great  extent  the  common  property  of  all  fully-developed  persons.  But 
the  technique  of  the  finished  singer  or  musician,  of  the  swordsman  or 
acrobat,  and  even  the  operative  skill  of  the  surgeon,  are  in  large  part  the 
outcome  of  a  special  and  acquired  agiUty  of  mind  or  body,  in  virtue  of 
which  highly-complicated  co-ordinated  movements  are  promptly  deter- 
mined on  and  immediately  executed. 

With  such  special  and  elaborate  movements  it  is  impossible  to  occupy 
ourselves  in  a  book  like  this.  Their  number  may  be  almost  indefinitely 
extended,  and  their  nature  almost  infinitely  varied,  by  the  needs  and 
training  of  special  trades  and  professions.  It  will  be  sufficient  for  our 
purpose  to  sketch  in  a  few  words  the  mechanism  of  one  or  two  of  the 
most  common  and  fundamental  co-ordinations  of  muscular  effort, 
passing  over  the  rest  with  the  general  statement  that  the  more  refined 
and  complex  movements  are  in  general  brought  about,  not  by  the  abrupt 
contraction  of  crude  anatomical  groups  of  muscles,  but  by  the  contrac- 
tion of  portions  of  muscles,  perhaps  even  single  fibres  or  small  bundles 
of  fibres,  while  the  rest  remain  relaxed.  The  excitation  may  gradually 
wax  and  wane  as  the  different  stages  of  the  movement  require.  Antago- 
nistic muscles  may  be  called  into  play  to  balance  and  tone  down  a  con- 
traction which  might  otherwise  be  too  abrupt. 

Many  interesting  illustrations  of  this  process  of  '  give  and  take  ' 
between  opposing  muscles  have  been  reported,  especially  by  Sherring- 
ton. Some  have  been  already  alluded  to  in  discussing  reflex  move- 
ments (p.  875).  One  or  two  additional  observations  may  be  given  here. 
In  the  cortex  cerebri,  as  we  shall  see  (pp.  919,  931),  there  is  an  area  in 
the  frontal  region,  and  another  in  the  occipital  region,  stimulation  of 
which  gives  rise  to  conjugate  deviation  of  the  eyes — that  is,  rotation  of 
both  eyes — ^to  the  opposite  side.  Sherrington  divided  the  third  and 
fourth  cranial  nerves  in  monkeys — say  on  the  left  side.  The  external 
rectus, which  is  supplied  by  the  sixth  nerve,  caused  now  by  its  unopposed 
contraction  external  squint  of  the  left  eye.  When  either  of  the  cortical 
areas  referred  to,  or  even  the  subjacent  portion  of  the  corona  radiata, 
was  stimulated  on  the  left  side,  both  eyes  moved  towards  the  right,  the 
left  eye,  however,  only  reaching  the  iniddle  line — that  is,  the  position  in 
which  it  looked  straight  forward.  The  same  thing  was  observed  when 
the  animal,  after  complete  recovery  from  the  operation,  was  caused  to 
voluntarily  turn  its  eyes  to  the  right  by  the  sight  of  food.  Here  an 
inhibitory  influence  must  have  descended  the  fibres  of  the  abducens,  the 
only  ner\'Ous  path  connected  with  the  extrinsic  muscles  of  the  left  eye, 
and  the  relaxation  of  the  left  external  rectus  must  have  kept  accurate 
step  with  the  contraction  of  the  right  internal  rectus.  Hering  has  made 
an  exhaustive  analysis  of  the  co-ordinated  movements  concerned  in 
opening  and  closing  the  hand  in  monkeys.  These  movements  can  be 
produced  by  stimulation  of  the  cortex  or  the  internal  capsule,  but  not 


FUNCTIONS  01-   THE  BRAIN  947 

by  stimulation  of  the  anterior  spinal  roots.  When  the  hand  is  opened 
the  muscles  that  open  it  are  excited,  and  those  which  close  it  are  in- 
hibited from  the  cortex. 

Reaction  Time. — Just  as  in  a  reflex  act  a  certain  measureable 
time  {reflex  time)  is  taken  up  by  the  changes  that  occur  in  the  lower 
nervous  centres,  so  we  may  assume  that  in  all  psychical  processes 
the  element  of  time  is  involved.  And,  indeed,  when  the  interval 
that  elapses  between  the  application  of  a  stimulus  and  the  signal 
which  announces  that  it  has  been  felt  {reaction  time)  is  measured, 
it  is  found  that  for  the  cerebral  processes  associated  with  the  per- 
ception of  the  simplest  sensation  and  the  production  of  the  simplest 
voluntary  contraction  it  is  longer  than  the  time  which  the  spinal 
centres  require  for  the  elaboration  of  even  complex  and  co-ordinated 
reflex  movements.  Suppose,  e.g.,  that  the  stimulus  is  an  induction 
shock  applied  to  a  given  point  of  the  skin,  and  that  the  signal  is  the 
closing  of  the  circuit  of  an  electro- magnet,  then,  if  both  events  are 
automatically  recorded  on  a  revolving  drum,  the  interval  can  be 
readily  determined.  It  is  evident  that  this  includes,  not  only  the 
time  actually  consumed  in  the  central  processes,  but  also  the  time 
required  for  the  afferent  impulse  to  reach  the  brain,  and  the  efferent 
impulse  the  hand,  along  with  the  latent  period  of  the  muscles.  The 
time  taken  up  in  these  three  events  can  be  approximately  calculated, 
and  when  it  is  subtracted,  the  remainder  represents  the  reduced  or 
corrected  reaction  time — that  is,  the  interval  actually  spent  in  the 
centres  themselves.  This  is  by  no  means  a  constant.  It  is  in- 
fluenced not  only  by  the  degree  of  complexity  of  the  psychical  acts 
involved,  and  the  mental  attitude  of  the  person  (whether  he  expects 
the  stimulus  or  is  taken  by  surprise,  whether  he  has  to  choose 
between  several  possible  kinds  of  stimuli  and  respond  to  only  one, 
etc.),  but  it  varies  also  for  different  kinds  of  sensation,  for  the  same 
sensation  at  different  times,  and,  as  is  recognized  in  the  personal 
equation  of  astronomers,  in  different  individuals.  For  sensations 
of  touch  and  pain  it  may  be  taken  as  one-ninth  to  one-fifth,  for 
hearing  one-eighth  to  one-sixth,  and  for  sight  one-eighth  to  one- 
fifth  of  a  second.  So  that  the  proverbial  quickness  of  thought  is 
by  no  means  great,  even  in  comparison  with  that  of. such  a  gross 
process  as  the  contraction  of  a  muscle  (one-tenth  of  a  second). 
Nor  is  it  the  case  that  the  man  '  of  quick  apprehension  '  has  always 
a  short  reaction  time,  or  the  dullard  always  a  long  one,  although  in 
all  kinds  of  persons  practice  will  reduce  it. 

Section  XI.— Fatigue  and  Sleep— Hypnosis. 

Sleep  and  Fatigue. — Certain  gland-cells,  certain  muscular  fibres, 
and  the  epithelial  cells  of  ciliated  membranes,  never  rest,  and 
perhaps  hardly  ever  even  slacken  their  activity.     But   in  most 


948 


THE  CENTRAL  NERVOUS  SYSTEM 


organs  periods  of  action  alternate  at  more  or  less  frequent  intervals 
with  periods  of  relative  repose.  In  all  the  higher  animals  the  central 
nervous  system  enters  once  at  least  in  the  twenty-four  hours  into 
the  condition  of  rest  which  we  call  sleep.  What  the  cause  of  this 
regular  periodicity  is  we  do  not  know.  It  is  accompanied  by 
changes  in  the  microscopical  appearance  of  the  nerve-cells.  Thus, 
Hodge  found  differences  between  the  cells  of  certain  portions  of  the 
cerebral  cortex  in  birds,  and  of  certain  ganglia  in  the  honey-bee  after 

a  long  day  of  work  and  after 
a  night's  rest.  Mann,  Lugaro, 
and  other  observers,  found 
similar  differences  in  the  cells 
of  the  cerebral  cortex  and  the 
anterior  horn,  and  DoUey  in 
the  Purkinje's  cells  of  the 
cerebellum  in  dogs  fatigued  by 
muscular  exercise  as  compared 
with  rested  dogs  (Fig.  382). 

According  to  Dolley,  there  is, 
as  a  result  of  continued  activity, 
at  first  a  steady  increase  of  the 
basic  chromatic  material.  This 
increase  affects  first  the  extra- 
nuclear  chromatin,  the  Nissl  sub- 
stance, which,  according  to  the 
most  modern  view,  is  really 
nuclear  substance  distributed 
through  the  cytoplasm,  and  func- 
tions as  such  (Goldschmidt) .  The 
size  and  number  of  the  granules 
are  increased,  and  some  of  the 
chromatic  material  is  diffused 
Effect  of  Fatigue  on  Nerve-CeUs  throughout  the  cytoplasm,  as  in- 
(Barker,  after  Mann).  Two  motor  cells  dicatcd  by  diffuse  stammg.  Then 
from  lumbar  cord  of  dog  fixed  in  sublimate  the  mtranuclear  chromatm  also 
and  stained  with  toluidin  blue.  a.  from  undergoes  an  increase,  and  the 
rested  dog;  i,  pale  nucleus;  2,  dark  Nissl  size  of  the  cell  is  increased  too. 
spindles  ;  3,  bundles  of  nerve  fibrils.  In  moderate  activity  the  change 
6,  from  the  fatigued  dog;  4,  dark  shrivelled  goes  no  farther.  At  this  stage 
nucleus;  5,  pale  spindles.  the  cell  is  hyperchromatic— f.e., 

as  compared  with  a  normal 
resting  cell  it  contains  an  excess  of  chromatin.  The  production  of 
chromatin  having  reached  the  maximum  of  which  the  nucleus  is 
capable,  and  fimctional  activitj^  wliich  entails  the  using  up  of  the 
extranuclear  chromatin,  still  continuing,  the  total  chromatin  content 
begins  to  diminish,  first  in  the  nucleus,  through  the  passage  of 
its  chromatin  into  the  cytoplasm  to  recruit  the  Nissl  substance,  then 
in  the  cytoplasm  as  well.  Accompanying  the  disappearance  of  the 
chromatic  material  there  is  diminution  in  the  size  of  both  cell  and 
nucleus,  but  especially  of  the  niicleus,  so  that  the  normal  proportion 
between  volume  of  cell  and  volume  of  nucleus  (nucleus-plasma  relation 
of  Hertwig)  is  disturbed  in  favour  of  the  cytoplasm.     Both  cell  and 


FATIGUE  AND  SLEEP— HYPNOSIS  949 

nucleus  become  irregular  in  outline  or  crcnatcd.  Later  on,  and,  i1 
would  seem,  rather  abruptly,  swelling  of  the  nucteus  and ,  after  some  time, 
of  the  cytoplasm  occurs.  This  is  due  to  oedema,  and  may  be  taken  tc 
indicate  an  upset  of  their  normal  osmotic  relations.  '1  he  earlier  occur- 
rence of  oedema  in  the  nucleus  leads  to  another  change  in  the  nucleus- 
plasma  relation,  which  is  now  disturbed  in  favour  of  the  nucleus.  In  the 
measure  in  which  fatigue  progresses  the  extranuclcar  chromatic  material 
continues  to  be  used  up,  and,  in  spite  of  its  replenishment  from  the 
nucleus,  it  almost  or  entirely  vanishes  from  the  cytoplasm.  Then 
follows  what  is  perhaps  a  '  last  effort  '  on  the  part  of  the  nucleus  to 
supply  the  cytoplasm,  in  the  form  of  a  discharge  of  chromatic  substance, 
which  first  masses  itself  around  the  outside  of  the  nuclear  membrane, 
and  thence  gradually  ditluscs  into  the  cytoplasm.  With  the  using  up 
of  this  supply  all  the  basic  chromatic  material  of  the  cell,  except  that  in 
the  karyosome  (nucleolus),  is  exhausted.  Finally,  this  too  is  yielded 
up  to  the  cytoplasm,  and  with  its  consumption  there  remains  a  totally 
exhausted  cell,  tlevoid  of  basic  chromatin  and  incapable  of  recuperation. 
According  to  Pugnet,  even  in  extreme  fatigue,  as  when  dogs  were 
caused  to  run  forty  to  nearly  sixty  miles  in  a  special  apparatus,  the 
changes  varied  greatly  in  degree  in  different  cortical  cells,  from  mere 
diminution  of  the  chromatic  substance  to  complete  disappearance  of  it 
and  such  disintegration  of  the  cell  as  must  have  precluded  its  recover^', 
had  the  animal  been  allowed  to  live.  Many,  and  indeed  most,  of  the 
cortical  cells  were  quite  unaffected.  Histological  alterations  may  also 
be  caused  in  sympathetic  ganglion  cells  by  prolonged  artificial  stimula- 
tion of  the  nerves  connected  with  the  ganglia.  Experiments  on  fatigue 
changes  in  the  cells  of  the  spinal  ganglia  after  electrical  excitation  of  the 
posterior  root-fibres  are  less  decisive,  some  observers  having  obtained 
positive,  others  negative,  results  (p.  885). 

Theories  of  the  Causation  of  Sleep. — (i)  Some  have  suggested  that  sleep 
is  induced  by  the  using  up  of  substances  necessary  for  the  functional 
activity  of  the  neurons — e.g.,  the  stored -iip  or  intramolecular  oxygen — 
or  by  tlie  action  of  the  waste  products  of  the  tissues,  and  especially  lactic 
acid,  when  they  accumulate  beyond  a  certain  amount  in  the  blood,  or  in 
the  nervous  elements  themselves. 

(2)  Others  have  looked  for  an  explanation  to  vascular  changes  in  the 
brain,  but  so  far  are  the  possible  causes  of  such  changes  from  being 
understood,  that  it  is  even  yet  a  question  whether  in  sleep  the  brain  is 
congested  or  ana?mic.  Certain  writers  have  settled  this  question  by  the 
summary  statement  that  when  the  brain  rests  the  quantity  of  blood  in 
it  must  be  supposed  to  be  diminished,  as  in  other  resting  organs.  But 
this  is  a  fallacious  argument.  For  when  the  whole  body  rests,  as  it  does 
in  sleep,  it  has  as  much  blood  in  it  as  when  it  works;  in  sleep,  therefore, 
if  some  resting  organs  have  less  blood  than  in  waking  life,  other  resting 
organs  must  have  more;  and  it  is  the  province  of  experiment  to  decide 
which  are  congested  and  which  anamic.  In  coma,  a  pathological  con- 
dition which  in  some  respects  has  analogies  to  profound  and  long- 
continued  sleep,  the  brain  is  congested,  and  the  proper  elements  of  the 
nervous  tissue  presumably  compressed.  And  artificial  pressure  (applied 
by  means  of  a  distensible  bag  introduced  through  a  trephine  hole  into 
the  cranial  cavity)  may  cause  not  only  unconsciousness,  but  absolute 
ancHRsthesia.  But  it  is  possible  that  this  artificial  increase  of  intra- 
cranial pressure  may  produce  its  effects  by  rcntlering  the  brain  anjcmic, 
and  it  has  been  actually  observed  that  the  retinal  \cssels,  as  seen  with 
the  ophthalmoscope,  and  the  vessels  of  the  pia  mater  exjwsed  to  direct 
observation  in  man  by  disease  of  the  bones  of  the  skull,  or  in  animals  by 
operation,  shrink  during  sleep.     Statements  to  the  contrary  may  be  due 


950  THE  CENTRAL  NERVOUS  SYSTEM 

to  neglecting  the  influence  of  difference  of  position  in  tHe  sleeping  and 
waking  states.  In  sleeping  children  the  fontanelle  sinks  in,  an  indica- 
tion that  the  intracranial  pressure  is  reduced.  Observations  with  the 
plethysmo graph  have  shown  that  the  arm  swells  in  sleep,  and  shrinks 
when  the  sleeper  awakes,  or  even  when  he  is  subjected  to  sensory  stimuli 
not  sufficient  to  arouse  him — e.g.,  a  tune  played  by  a  musical-box 
(Howell).  The  tone  of  the  vaso-motor  centre  is  therefore  diminished, 
and  the  arterial  pressure  falls  during  sleep.  But  a  fall  of  general  arterial 
pressure  is  usually  accompanied  by  a  diminution  of  the  quantity  of 
blood  passing  through  the  brain.  So  that  the  balance  of  evidence  is  in 
favour  of  the  view  that  sleep  is  associated  with  a  certain  degree  of  cerebral 
aneemia. 

As  to  the  nature  of  the  relation  between  the  two  conditions,  it  has 
been  suggested  that  the  anaemia  is  produced  by  fatigue  of  the  vaso- 
motor centre,  which  causes  it  to  relax  its  grip  upon  the  peripheral  blood- 
vessels, and  that  the  condition  of  the  cortical  nerve-cells  which  we  call 
sleep  is  directly  produced  by  the  lack  of  blood.  But  there  does  not 
appear  to  be  any  good  reason  for  believing  that  the  vaso-motor  centre 
is  more  susceptible  of  fatigue  than  the  higher  cerebral  centres.  On  the 
contrary,  it  is  probable  that  the  bulbar  centres  are  less  delicately 
organized  and  more  resistant  than  the  higher  centres.  In  any  case,  if 
the  cerebral  nerve-cells  '  go  to  sleep  '  because  their  blood-supply  is 
diminished,  ought  we  not  to  look  for  a  similar  cause  for  diminished 
activity  of  the  vaso-motor  centre  ?  Or  if  the  answer  is  made  that  the 
activity  of  the  vaso-motor  cells  is  directly  lessened  by  fatigue,  or  by  the 
cessation  of  external  stimuli,  why  should  not  this  be  the  case  also  for  the 
cortical  cells  ?  It  can  be  shown  by  means  of  the  sphygmomanometer 
(p.  114)  that  the  fall  of  arterial  pressure  is  not  essentially  connected  with 
sleep,  but  is  produced  by  the  bodily  rest  and  warmth  which  accompany 
it.  Further,  even  a  great  diminution  in  the  supply  of  blood  going  to  the 
brain  is  not  necessarily  followed  by  sleep.  For  example,  both  carotids 
and  both  vertebral  arteries  may  frequently  be  tied  in  dogs  at  the  same 
time  without  producing  any  symptoms,  the  anastomosis  of  the  superior 
intercostal  arteries  with  the  anterior  spinal  artery  providing  a  sufficient 
channel  for  the  blood  absolutely  required  by  the  brain.  Monkeys  after 
ligation  of  both  carotids  may  be  most  alert  and  active.  To  produce 
sopor  in  animals  the  cortical  circulation  must  be  reduced  almost  to  the 
vanishing-point,  and  to  a  far  greater  degree  than  ever  occurs  in  sleep 
(Hill).  We  must,  therefore,  conclude  that  although  sleep  is  normally 
associated  with  some  aneemia  of  the  brain,  it  is  not  directly  caused  by  it. 
The  cortical  centres  go  to  sleep  because  they  are  '  tired,'  or  because  the 
stimuli  which  usually  excite  them  have  ceased,  and  not  because  their 
blood-supply  is  diminished. 

(3)  The  idea  that  the  dendrites  are  contractile,  and  by  pulling  them- 
selves in,  and  thus  breaking  certain  ner\'ous  chains,  cause  sleep,  is  a 
mere  theory,  unsupported  by  any  real  evidence.  The  same  is  true  of 
the  notion  that  the  fibrils  of  the  neuroglia  insinuate  themselves  into  the 
'  joints,'  by  which  one  neuron  comes  into  contact  with  another,  and, 
acting  as  insulating  material,  block  the  nerve-impulses. 

In  general,  the  depth  of  sleep,  as  measured  by  the  intensity  of  sound 
needed  to  awaken  the  sleeper,  increases  rapidly  in  the  first  hour,  falls 
abruptly  in  the  second,  and  then  slowly  creeps  down  to  its  minimum, 
which  it  reaches  just  before  the  person  awakens.  As  to  the  amount  of 
sleep  required,  no  precise  rules  can  be  laid  down.  It  varies  with  age, 
occupation,  and  perhaps  climate.  An  infant,  whose  main  business  is  to 
grow,  spends,  or  ought  to  spend,  if  mothers  were  wise  and  feeding-bottles 
clean,  the  greater  part  of  its  time  in  sleep.     The  man,  whose  main 


FATIGUE  AND  SLEEP—HYFNOSIS  951 

business  it  is  to  work  with  his  hands  or  brain,  requires  his  full  tale  of 
eight  hours'  sleep,  but  not  usually  more.  Thcdry  and  exhilarating  air 
of  some  of  the  inland  jx)rtions  of  North  America,  and  perhaps  the  plains 
of  Victoria  and  New  South  Wales,  incites,  and  possibly  enables  a  new- 
omcr  to  live  for  a  considerable  period  with  less  than  his  ordinary 
amount  of  sleep.  Idiosyncrasy,  and  perhaps  to  a  still  greater  extent 
habit,  have  also  a  marked  influence.  The  great  Napoleon,  in  his 
heyday,  never  slept  more  than  four  or  five  hours  in  the  twenty-four. 
Five  or  six  hours  or  less  was  the  usual  allowance  of  Frederick  of  Prussia 
throughout  the  greater  part  of  his  long  and  active  life. 

Hypnosis  is  a  condition  in  some  respects  allied  to  natural  slumber; 
but  instead  of  the  activity  of  the  whole  brain — or  perhaps  we  should 
rather  say,  the  whole  activity  of  the  brain — being  in  abeyance,  the 
susceptibility  to  external  impressions  remains  as  great  as  in  waking  life, 
or  may  be  even  increased,  while  the  critical  faculty,  which  normally 
sits  in  judgment  on  them,  is  lulled  to  sleep.  The  condition  can  be 
induced  in  many  ways — by  asking  the  subject  to  look  fixedly  at  a  bright 
object,  by  closing  his  eyes,  by  occupying  his  attention,  by  a  sudden  loud 
sound  or  a  flash  of  light,  etc.  The  essential  condition  is  that  the  person 
should  have  the  idea  of  going  to  sleep,  and  that  he  should  surrender  his 
will  to  the  operator.  In  the  hypnotic  condition  the  subject  is  extremely 
open  to  suggestions  made  by  the  operator  with  whom  he  is  en  rapport. 
He  adopts  and  acts  upon  them  without  criticism.  If,  for  example,  the 
hypnotizer  raises  the  subject's  arm  above  his  head,  and  suggests  that  he 
cannot  bring  it  down  again,  it  stays  fixed  in  that  position  for  a  long  time 
without  any  appearance  of  fatigue;  or  the  whole  body  may  be  thrown, 
on  a  mere  hint,  into  some  unnatural  pose,  in  which  it  remains  rigid 
as  a  statue.  Suggested  hemiplegia  or  hemianasthesia,  or  paralysis  of 
motion  and  sensation  together  or  apart  in  limited  areas,  can  also  be 
realized ;  and  surgical  operations  ha\e  been  actually  performed  on 
hy]")notized  persons  without  any  appearance  of  suffering.  If,  on  the 
other  hand,  the  operator  suggests  that  the  subject  is  undergoing  intense 
pain,  he  will  instantly  take  his  cue,  writhing  his  body,  pressing  his  hands 
upon  his  head  or  breast,  and  in  all  respects  behaving  as  if  the  suggestion 
were  in  accord  with  the  facts.  If  he  is  told  that  he  is  blind  or  deaf,  he 
will  act  as  if  this  were  the  case.  If  it  is  suggested  that  a  person  actually 
present  is  in  Timbuctoo,  the  subject  will  entirely  ignore  him,  will  leave 
him  out  if  told  to  count  the  persons  in  the  room,  or  try  to  walk  through 
him  if  asked  to  move  in  that  direction.  What  is  even  more  curious  is 
that  the  organic  functions  of  the  body  are  also  liable  to  be  influenced  by 
suggestion.  A  postage-stamp  was  placed  on  the  skin  of  a  hypnotized 
person,  and  it  was  suggested  that  it  would  raise  a  blister.  Next  day  a 
blister  was  actually  found  beneath  it.  The  letter  K,  embroidered  on  a 
piece  of  cloth,  was  suggested  to  be  red-hot.  The  left  shoulder  was  then 
'  branded  *  with  it,  and  on  the  right  shoulder  appeared  a  facsin)ile  of  the 
K  as  if  burnt  with  a  hot  iron.  The  secretions  can  be  increased  or 
diminished,  subcutaneous  hamorrhagcs,  veritable  stigmata,*  can  be 
caused,  and  many  of  the  '  miracles  '  of  Lourdes  and  other  shrines,  ancient 
and  modem,  repeated  or  surpassed  by  the  aid  of  hypnotic  suggestion. 
Hypnotism  has  also  been  practically  employed  in  the  treatment  of 
various  diseases,  and  particularly  in  functional  derangements  of  the 

•  I.e.,  bleeding  spots  on  the  skin  generally  corresponding  to  the  wounds 
of  Christ.  In  the  well-known  case  of  Louise  Latour.  which  excited  great 
interest  in  France  in  186S,  blisters  lirst  appeared;  they  burst,  and  then  there 
was  bleeding  from  the  true  skin.  The  probable  explanation  is  that  she  con- 
centrated her  attention  on  these  parts  of  her  body  and  so  influenced  them, 
perhaps  by  causing  congestion  through  the  vaso-motor  centre. 


952 


THE  CENTRAL  NERVOUS  SYSTEM 


nervous  system.  But  care  and  judgment  are  necessary  on  the  part  of 
the  operator,  and  althoiigh  as  a  rule  there  is  no  difficulty  in  putting  an 
end  to  the  condition  by  a  suitable  suggestion,  it  is  said  that  in  rare 
instances  grave  mischances  have  occurred.  There  seems  to  be  no  ground 
for  the  opinion  that  women  are  more  easily  hypnotized  than  men.  Out 
of  more  than  a  thousand  persons,  Liebault  found  only  seventeen  abso- 
lutely refractory. 


Section  XII. — Size  of  Brain  and  Intelligence — Circulation 
IN  and  Resuscitation  of  Central  Nervous  System  after 
Anemia — Chemistry  of  Nervous  Activity — Cerebro-spinal 
Fluid. 

Relation  of  Size  of  Brain  to  Intelligence. — While  it  is  the  case 
that  some  men  of  great  abiUty  have  had  remarkably  heavy  and 
richly  convoluted  brains,  it  would  seem  that  in  general  neither  great 
size  nor  any  other  obvious  anatomical  peculiarity  of  the  cerebrum 
is  constantly  associated  with  exceptional  intellectual  power.  In 
the  animal  kingdom,  as  a  whole,  there  is  undoubtedly  some  relation 
between  the  status  of  a  group  and  the  average  brain  development 
within  the  group.  But  that  this  is  a  relation  which  is  complicated 
by  other  circumstances  than  the  mere  degree  of  intelligence  is 
sufficiently  shown  by  the  fact  that  a  mouse  has  more  brain,  in  pro- 
portion to  its  size,  than  a  man,  and  thirteen  times  more  than  a  horse ; 
while  both  in  the  rabbit  and  sheep  the  ratio  of  brain-weight  to  body- 
weight  is  nearly  twice  as  great  as  in  the  horse,  in  the  dog  only  half 
as  great  as  in  the  cat,  and  not  very  much  more  than  in  the  donkey. 
The  following  tables,  too,  which  illustrate  the  weight  of  the  brain 
in  man  at  different  ages,  show  that,  although  we  might  give  '  the 
infant  phenomenon  '  an  anatomical  basis,  we  should  greatly  over- 
rate the  intellectual  acuteness  of  the  average  baby  if  we  were  to 
measure  it  by  the  ratio  of  brain  to  body- weight  alone. 


Age. 

Brain-weight. 

Age. 

Brain-weight. 

I  year 

885  grm. 

8 

years       .  .      1,045  grm. 

2  years 

909      ,, 

10 

..       1,315      .. 

3       ., 

1,071       ,, 

II 

..        1,168      ,, 

4       .. 

1.099      ,. 

12 

..       1,286      ,, 

5       .. 

1,033       ., 

13 

..        1,505       .. 

6       ,, 

1. 147       .. 

14 

..        1,336      -> 

7       .. 

1,201       ,, 

15 

..        1,414      .. 

BiSCHOFF. 

Brain-we 

ight- 

Brain-weight — 

Br 

ain-weight—           Brain-weight — 

Ajre. 

Mer 

1. 

Women. 

Age. 

Men.                             Women. 

£0-19 

.  .    1,411 

grm 

..    1,219  grm. 

50 

-59 

.  .  I 

389  grm.   ..   1,239  grm 

20-29 

..    1,419 

,, 

..   1,260     ,, 

60 

-69 

.  .  I 

292     ,,       ..    1. 219     ,, 

30-39 

..    1,424 

,, 

..    1,272     ,, 

70 

-79 

.  .  I 

254     .,       ..    1,129     ,, 

40-49 

.  .    1,406 

" 

..   1.272     ,, 

80 

-90 

.  .  I 

303     ..      ••       898     „ 

HUSCHKE. 

THE  CEREBRAL  CIRCULATION  953 

In  some  small  birds  the  ratio  is  as  high  as  i  :  12,  in  large  birds 
as  low  as  i  :  1,200;  in  certain  fishes  a  gramme  of  brain  has  to  serve 
for  over  5  kilos  of  body.  As  a  rule,  especially  within  a  given  species, 
the  brain  is  proportionally  of  greater  size  in  small  than  in  large 
animals.  It  is  to  be  supposed  that  quality  as  well  as  quantity  of 
brain  substance  is  a  potent  factor  in  iletermining  tht*  degree  of 
mental  capacity. 

The  Cerebral  Circulation. — The  arrangement  of  the  cerebral  blood- 
vessels has  certain  j)eciiHiiritics  which  it  is  of  importance  to  remember 
in  connection  with  the  study  of  the  diseases  of  the  brain,  many  of  which 
are  caused  by  lesions  in  the  vascular  system — haemorrhage  or  embolism. 
Four  great  arterial  trunks  carry  blood  to  the  brain, two  internal  carotids 
and  two  vertebrals.  The  vertcbrals  unite  at  the  base  of  the  skull  to 
form  the  single  mesial  basilar  artery,  which,  running  foi^vard  in  a  groove 
in  the  occipital  bone,  splits  into  the  two  posterior  cerebral  arteries. 
Each  carotid,  passing  in  through  the  carotid  foramen,  divides  into  a 
middle  and  an  anterior  cerebral  artery;  the  latter  runs  forward  in  the 
great  longitudinal  fis.^ure,  the  former  lies  in  the  fissure  of  Sylvius.  A 
communicating  branch  joins  the  middle  and  posterior  cerebrals  on  each 
side,  and  a  short  loop  connects  the  two  anterior  cerebrals  in  front.  In 
this  way  a  hexagon  13  formed  at  the  base  of  the  brain,  the  so-called 
circle  of  Willis.  While  the  anastomosis  between  the  large  arteries  is 
thus  very  free,  the  opposite  is  true  of  their  branches.  All  the  arteries 
in  the  substance  of  the  brain  and  cord  are  '  end-arteries  ' — that  is  to 
say,  each  terminates  %vithin  its  area  of  distribution  without  sending 
communicating  branches  to  make  junction  with  its  neighbours.  The 
conso(|ucnce  of  these  two  anatomical  facts  is:  (i)  that  interference  with 
the  blood-supply  of  the  brain  between  the  heart  and  the  circle  of  Willis 
does  not  readily  produce  s^Tuptoms  of  cerebral  anaemia;  (2)  that  the 
blocking  of  any  of  the  arteries  which  arise  from  the  circle  or  any  of  their 
branches  leads  to  destruction  of  the  area  supplied  by  it.  Nearly  all 
dogs  recover  after  ligation  in  one  operation  of  both  carotids  and  both 
vertebral  arteries.  In  monkeys  both  carotids  may,  as  a  rule,  be  safely 
tied,  and  one  carotid  in  man.  If,  in  addition  to  the  two  carotids,  one 
vertebral  be  ligatcd  at  the  same  time  in  the  monkey,  sopor  results,  and 
this  is  generally  followed  by  extensor  rigidity',  coma,  and  death  in 
twenty-four  hours.  In  one  case  a  monkey  survived  this  triple  ligation, 
but  became  demented.  The  motor  paralysis  and  rigidity  were  much 
greater  than  in  the  dog.  In  the  condition  of  partial  anamia  the  cortex 
is  more  excitable  than  normal,  but  the  excitability  disappears  at  once 
"vhen  the  anaemia  is  rendered  complete  (Hill). 

The  basal  ganglia  are  fed  by  twdgs  from  the  circle  of  Willis  and  the 
beginning  of  the  posterior,  middle,  and  anterior  cerebral  arteries.  Of 
these  the  most  important  are  the  lenticulo-striate  and  lenticulo-optic 
branches  of  the  middle  cerebral,  which  are  given  oil  near  its  origin,  and 
run  through  the  lenticular  nucleus  into  the  internal  capsule,  and  thence 
to  the  caudate  nucleus  and  optic  thalamus  respectively.  The  chief  part 
of  the  blood  from  the  circle  of  Willis  is  carried  by  the  tliree  great  cerebral 
arteries  over  the  cortex  of  the  brain.  The  white  matter,  with  the 
exception  of  that  in  the  immediate  neij^hbourhood  of  the  basal  ganglia, 
is  nourished  by  straight  arteries  which  penetrate  the  cortex.  The 
middle  cerebral  supplies  the  whole  of  the  parietal  as  well  as  that  portion 
of  the  frontal  lobe  which  lies  inmiediately  in  front  of  tlie  fissure  of 
Rolando  and  the  upper  part  of  the  temjxiral  lobe.     The  rest  of  the 


954  THE  CENTRAL  NERVOUS  SYSTEM 

frontal  lobe  is  supplied  by  the  anterior  cerebral,  and  the  occipital  lobe, 
with  the  lower  part  of  the  temporal  lobe,  by  the  posterior  cerebral. 
The  medulla  oblongata,  cerebellum,  and  pons  are  fed  from  the  verte- 
brals  and  the  basilar  artery  before  the  circle  of  Willis  has  been  formed. 

Resuscitation  of  the  Central  Nervous  System  after  Total  Anaemia. 
— Complete  temporary  anaemia  of  the  brain  and  upper  cervical 
cord  can  be  produced  in  most  cats  by  passing  temporary  ligatures 
around  the  innominate  artery  and  left  subclavian  proximal  to 
the  origin  of  the  vertebral  artery.  Artificial  respiration  is  main- 
tained through  a  tube  passed  through  the  glottis.  The  eye  reflexes 
disappear  very  quickly,  and  a  period  of  high  blood-pressure  imme- 
diately follows  the  occlusion.  A  fall  of  pressure  succeeds,  due  to 
vagus  inhibition  of  the  heart,  and  this  is  followed  by  a  second  rise 
after  the  vagus  centre  succumbs  to  the  anaemia.  Respiration  stops 
temporarily  (in  twenty  to  sixty  seconds)  after  occlusion;  then 
follows  a  series  of  strong  gasps,  and  finally  cessation  of  all  respiratory 
movements.  The  blood-pressure  slowly  falls  to  a  level  which  is  then 
maintained  approximately  constant  for  the  remainder  of  the  occlu- 
sion period.  The  anterior  part  of  the  cord  and  the  encephalon  lose 
all  function;  no  reflexes  can  be  elicited  from  this  part  of  the  central 
nervous  system.  The  intra-ocular  tension  is  much  reduced,  and  the 
cornea  is  characteristically  wrinkled. 

When  the  cerebral  circulation  is  restored  by  releasing  the  vessels, 
the  general  arterial  pressure  soon  begins  to  rise  if  the  period  of 
occlusion  has  not  overstepped  the  limit  of  successful  cardio-vascular 
resuscitation.  The  respiration  returns  suddenly,  the  time  of 
return  depending  on  the  length  of  the  occlusion  and  on  other  factors. 
The  respiratory  rate,  at  first  slow,  soon  becomes  normal,  and  then 
more  rapid  than  normal.  The  eye-reflexes  reappear  more  gradu- 
ally; the  intra-ocular  tension  increases,  and  the  shrunken  cornea 
becomes  smooth  and  hard.  The  anterior  part  of  the  cord  recovers 
its  functions  gradually;  the  reflexes  connected  with  it  return,  first 
the  homonymous,  then  the  crossed.  A  short  period  of  quiet  follows ; 
then  spasms  of  the  skeletal  muscles  appear,  gradually  increase  in 
severity  and  extent,  and  terminate  in  {a)  death,  {b)  partial,  or 
(c)  complete  recovery.  In  partial  recovery,  disturbances  of  loco- 
motion, such  as  walking  in  a  circle,  paralysis,  apparent  dementia 
or  loss  of  intelligence,  and  loss  of  sight  or  hearing,  may  be  observed. 
Voluntary  movements  of  the  head,  neck,  shoulders,  and  fore-limbs 
have  been  seen  eight  minutes  after  release  from  an  occlusion  of  six 
minutes.  Bhndness  has  been  observed  without  loss  of  the  pupillary 
light  reflex.  In  this  case  the  visual  cortex  would  seem  to  have 
suffered  more  than  the  lower  centres,  an  illustration  of  a  general 
rule.  Complete  recovery  is  rare  after  total  anaemia  lasting  as  much 
as  fifteen  minutes,  and  has  not  been  observed  after  an  anaemia  of 
twenty  minutes.     Ten  to  fifteen  minutes  of  total  anaemia  represent 


CHEMISTRY  OF  NERVOUS  ACTIVITY 


933 


the  limit  beyond  which  recovery  of  the  brain,  and  therefore  successful 
resuscitation  of  the  animal,  cannot  be  expected. 

Chemistry  of  Nervous  Activity. — Of  this  we  are  practically  ignorant. 
The  percentage  composition  of  the  solids  and  the  percentage  of 
water  in  tlie  brains  of  three  persons  of  different  ages  are  ex- 
hibited in  the  following  table  (W.  Koch): 


Child  6  Weeks 
(Brain  640  Grms.). 

Child  2  Years 
(Grain  1,100  Grms.). 

Adult  19  Years 
(Brain  1,670  Grms.). 

Whole  Brain. 

Grey.  |  White. 

1 

Whole 
Brain.* 

Grey. 

White. 

Wh..le 
Brain,  t 

Proteins 
Extractives     . . 
Ash       . . 
Lecithins      and 
kephaUns    . . 
Cercbrins 
Lipoid  S  as  SO4 
Cholesterint 

46-6 
12-0 

8-3 

24-2 
69 
O-I 

1-9 

48-4 
lO-O 

5-8 

247 
8-6 
o-i 

2-4 

31-9 
5-9 
3-2 

26-3 
17-2 

0-5 
15-0 

40-1 
8-0 

4-5 
25-5 

12-9 

0-3 
8-7 

47-1 
9-5 
5-9 

23-7 

8-8 

O-I 

4-9 

27-1 

3-9 

2-4 

31-0 

i6-6 
18-5 

37-1 

6-7 

4-1 

27-3 
12-7 

0-3 
11-7 

Water  . . 

88-78 

34-49  76-45 

80-47 

83-17 

69-67 

76-42  1 

The  next  table  shows  the  variations  in  the  content  of  water, 
solids,  and  protein  in  different  parts  of  the  nervous  system  (Halli- 
burton) : 


Water. 

Solids. 

Percenlage  of  Pro- 
teins ill  Solids. 

Cerebral  grey  matter 

83-5 

16-5 

51 

Cerebral  wliite  matter 

69-9 

30-1 

35 

Cerebellum 

79-8 

20-2 

42 

Spinal  cord  as  a  whole 

71-6 

28-4 

31 

Cervical  cord 

72-5 

27-5 

31 

Dorsal  cord 

69-8 

30-2 

28 

Lumbar  cord 

72-6 

27-4 

33 

Sciatic  nerves 

65-1 

34-9 

29 

The  grey  matter  of  the  cerebrum  in  the  adult  contains  8i  to 
86  per  cent,  of  wa+er,  the  white  matter  68  to  j2  per  cent.,  the 
brain  as  a  whole  8i  per  cent.,  the  spinal  cord  68  to  76  per  cent., 
and  the  peripheral  nerves  57  to  64  per  cent.  In  the  foetus  more 
water  is  present  (92  per  cent,  in  the  grey  and  87  per  cent,  in  the 
white  matter). 

The  superior  richness  of  the  grey  matter  in  proteins  and  the 
preponderance  of  water  in  it  are  the  chief  chemical  ix'culiarities 
which  distinguish  it  from  the  white  matter.  That  it  should  have 
♦  Calculated.  t  Calculated  by  difference. 


956  THE  CENTRAL  NERVOUS  SYSTEM 

a  high  protein  content  is  easily  understood,  for  the  protoplasmic 
structures,  the  nerve-cells,  are  situated  in  the  grey  matter.  But 
that  the  most  important  functions  should  have  their  seat  in  a  tissue 
containing  only  14  to  19  per  cent,  of  solids  is  surprising,  and  should 
warn  us  that  the  water  is  no  less  significant  a  constituent  of  living 
matter  than  the  solids,  and  that  it  is  not  the  mass  of  the  sohd 
substances  in  a  tissue  which  is  the  essential  thing,  but  the  whole 
colloid  complex,  which  cannot  be  constituted  without  the  water. 

Fresh  nervous  tissues  are  alkaline  to  litmus,  but  become  acid 
soon  after  death.  No  change  of  reaction  has  been  detected  during 
activity. 

That  oxygen  is  used  up  during  cerebral  activity  is  certain,  and 
when  the  brain  is  coloured  with  methylene  blue,  by  injecting  it 
into  the  circulation,  any  spot  of  it  which  is  stimulated  loses  the 
blue  colour,  the  pigment  being  reduced.  But  if.  the  animal  is  so 
deeply  narcotized  that  it  does  not  respond  to  stimulation,  the  change 
of  colour  does  not  occur. 

Cholin  (p.  360),  a  substance  which  can  be  derived  from  lecithin, 
is  believed  to  represent  one  of  the  waste  products  of  nervous  activity. 
Exceedingly  small  traces  of  it  are  present  in  normal  cerebro-spinal 
fluid,  and  in  certain  diseased  conditions  of  the  brain,  as  in  general 
paralysis,  the  quantity  is  said  to  be  notably  increased,  indicating 
an  increased  decomposition  of  lecithin.  The  fatty  acid  constituent 
of  lecithin  is  liberated  in  degenerating  nerve,  giving  rise  to  the 
reaction  with  osmic  acid  (p.  771).  Some  writers  assert  that  this 
increase  in  the  cholin  can  be  used  as  a  test  to  distinguish  organic 
nervous  disease  from  that  which  is  purely  functional.  But  the 
matter  is  in  dispute. 

Cerebro-spinal  Fluid. — The  cerebro-spinal  fluid,  which  fills  the 
ventricles  of  the  brain  and  the  central  canal  of  the  cord,  is  con- 
tinuous with  that  contained  in  the  subarachnoid  space  through  the 
foramen  of  Magendie,  an  opening  in  the  piece  of  pia  mater  that  helps 
to  roof  in  the  fourth  ventricle.  It  is  secreted  in  part  by  the  cubical 
cells  covering  the  choroid  plexus,  a  fold  of  pia  mater  which  projects 
into  each  lateral  ventricle.  Extracts  of  choroid  plexus,  when  in- 
jected intravenously,  increase  the  rate  of  secretion. 

This  action  is  dependent  upon  the  presence  of  some  substance  in 
the  choroid  plexus,  which,  however,  is  not  a  specific  product  of  the 
activity  of  the  plexus,  since  extracts  of  the  brain  produce  the  same 
effect.  It  may  therefore  be  some  product  of  the  metabolism  of  the 
brain  which  passes  to  the  choroid  plexus  and  stimulates  secretion 
by  the  epithelium.  The  substance  is  removed  from  the  fluid  by 
filtration  through  a  Chamberland  filter,  and  is  therefore  probably 
of  high  molecular  weight.  It  is  probable  that  variations  in  the  rate 
of  secretion  of  the  cerebro-spinal  fluid  by  the  choroid  plexus  are  more 
influential  in  governing  the  intracranial  pressure  than  variations  in 


PRACTICAL  EXERCISES  957 

the  arterial  and  venous  pressures.  The  idea  that  the  cranial  contents 
constitute  a  fixed  quantity,  without  the  power  of  contraction  or 
expansion,  can  no  longer  be  maintained  (Dixon  and  Halliburton). 

Cerebro-spinal  fluid  can  easily  be  obtained  in  man  by  lumbar 
puncture  with  a  hypodermic  needle  sufiiciently  long  to  enter  the 
subarachnoid  space  in  the  spinal  canal.  The  point  usually  selected 
for  the  puncture  is  between  the  fourth  and  fifth  lumbar  vertebra;. 
The  normal  pressure  of  the  fluid  is  such  that  it  trickles  out  by  drops, 
but  in  disease  it  is  sometimes  so  high  that  it  spurts  out  in  a  steady 
stream.  An  examination  of  the  fluid,  especially  for  leucocytes  or 
bacteria,  is  of  great  diagnostic  value  in  certain  conditions.  Nor- 
mally it  is  a  thin,  clear,  watery  fluid,  faintly  alkaline  in  reaction 
to  litmus,  and  with  a  specific  gravity  of  about  1004  to  1007.  It 
contains  the  ordinary  salts,  but  more  potassium  than  sodium,  unlike 
other  body  fluids;  a  very  small  amount  of  protein  (globuhn) — 
usually  about  01  per  cent. — and  a  little  dextrose  (>s^awratzki). 
Its  composition  is  evidently  different  from  that  of  ordinary  lymph. 
Only  a  few  lymphocytes  are  present  in  health,  but  in  some  diseases 
(ci«  in  general  paralysis  of  the  insane,  tabes,  and  cerebro-spinal 
syphilis)  a  marked  increase  occurs.  In  acute  cerebro-spinal  menin- 
gitis numerous  polymorphonuclear  leucocytes  are  found,  which  are 
absent  from  the  normal  fluid. 

The  depression  of  the  freezing-point  (A)  usually  lies  between 
—  o-6o°  and  065°  C.  In  a  case  of  hydroceplialus  it  was  -0-65°  C 
Normally,  cerebro-spinal  fluid  is  somewhat  hypertonic  to  the  blood- 
serum.  In  injury  of  the  cribriform  plate  of  the  ethmoid  bone  and 
also  in  some  cases  where  there  is  no  traumatic  injury,  the  fluid 
escapes  from  the  nose,  and  the  rate  of  its  formation  can  thus  be 
ascertained.  In  one  case  it  was  found  to  be  as  much  as  2  cc  to 
nearly  4  c.c  in  ten  minutes. 


PRACTICAL  EXERCISES  ON  CHAPTER  XVI, 

I.  Section  and  Stimulation  of  the  Spinal  Nerve-Roots  in  the  Frog. — {a) 
Select  a  large  frog  (a  bull-frog,  if  possible).  Pith  the  brain.  Fasten 
the  frog,  belly  down,  on  a  plate  of  cork.  Make  an  incision  in  the  middle 
line  over  the  spinous  processes  of  the  lowest  three  or  four  vertebra?, 
separate  the  muscles  from  the  vertebral  arches,  and  with  strong  scissors 
open  the  spinal  canal,  taking  care  not  to  injure  the  cord  by  passing  the 
blade  of  the  scissors  too  deeply,  l.xtend  the  opening  upwards  till  two 
or  three  posterior  roots  come  into  view.  Pass  line  silk  ligatures  under 
two  of  them,  tie,  and  divide  one  root  central  to  the  ligature,  the  other 
peripheral  to  it.  Stimulate  the  central  end,  and  reflex  movements  will 
occur.  Stimulate  the  peripheral  end:  no  eftect  is  i^roduced.  Now  cut 
away  the  exposed  posterior  roots  and  isolate  and  ligature  two  of  the 
anterior  roots,  which  are  smaller  than  the  posterior.  Stimulate  the 
central  end  of  one :  there  is  no  effect.  Stimulation  of  the  peripheral  end 
of  the  othej  causes  contractions  of  the  corresponding  muscles. 

{b)  Stimulation  of  the  roots  may  be  repeated  on  the  majnnial,  using 


958  THE  CENTRAL  NERVOUS  SYSTEM 

the  dog  employed  for  the  experiment  on  the  motor  areas  (p.  962). 
Place  the  animal,  belly  down,  and  insert  a  good-sized  block  of  wood 
between  it  and  the  board  at  the  level  of  the  lumbar  vertebrae  of  the 
spine.  Divide  the  skin  and  muscles  on  either  side  of  this  region  till  the 
laminae  of  the  vertebrae  are  exposed.  Snip  through  them  with  strong 
forceps,  and  open  the  spinal  canal,  exposing  a  length  of  cord  correspond- 
ing to  three  or  four  vertebrae.     Ligate  and  stimulate  the  roots  as  in  (a). 

2.  Reflex  Action  in  the  'Spinal  '  Frog. — Pith  the  brain  of  a  frog, 
destroying  it  down  to  the  posterior  third  of  the  medulla  oblongata, 
(i)  Note  the  position  of  the  limbs  immediately  after  the  operation,  and 
again  thirty  to  forty  minutes  later.  Its  hind-legs  possess  tone,  and  are 
drawTi  up  against  the  flanks.  The  animal  can  still  execute  certain 
co-ordinated  movements— e.g.,  pulling  away  its  leg  if  a  toe  is  pinched. 

\  The  power  of  maintaining  equilibrium  is  lost.  If  placed  on  its  back,  it 
'lies  there.  When  thrown  into  water  it  sinks  usually  without  any 
attempt  at  swimming.  Verify  the  following  facts,  using  mechanical 
stimulation  (pinching  the  toes  or  skin  of  the  leg) :  (a)  If  the  stimulus 
provokes  muscular  movements  only  on  one  side  of  the  body,  this  is 
usually  on  the  same  side  as  the  stimulated  point,  [b]  When  the  stimulus 
causes  reflex  movements  on  both  sides  of  the  body,  the  stronger  con- 
tractions are  on  the  side  to  which  the  stimulus  was  applied. 

Determine  whether  it  is  easier  to  obtain  movement  of  a  portion  of  the 
body  innervated  from  a  region  of  the  cord  above  the  level  of  the  stimu- 
lated nerves  or  below  that  level. 

(2)  With  electrical  stimuli  (using  a  coil  arranged  for  single  shocks  de- 
termine if  reflex  movements  are  elicited  by  a  single  induced  shock  ap- 
plied to  the  skin.  Verify  the  fact  that  a  series  of  shocks  is  more  efiicient, 
the  effects  of  the  separate  stimuli  being  summated  in  the  reflex  centres. 

(3)  To  test  the  effect  of  thermal  stimuli,  dip  the  leg  into  a  beaker  of 
warm  water.  Vary  the  temperature  of  the  water,  using  a  series  oi 
beakers  with  water  at  10°  C,  15°  C,  20°  C,  etc.,  above  the  temperature  of 
the  room.  Place  the  leg  for  a  moment  in  each,  and  determine  which  is  the 
most  efficient  stimulus.  Immediately  on  withdrawing  the  leg  from  each 
of  the  hot-water  beakers  immerse  it  in  a  beaker  of  water  at  room  tem- 
perature.    Finally,  dip  the  leg  into  a  beaker  of  cold  water,  and  heat  it 

I  gradually  to  a  temperature  at  which  a  reflex  was  previously  obtained. 
I  Probably  it  will  not  be  elicited  by  the  gradual  warming. 

(4)  '  Purposive  '  Movements. — Touch  the  skin  of  one  thigh  with  blot- 
ting-paper soaked  in  strong  acetic  acid.  The  leg  is  drawn  up,  and  the 
foot  moved  as  if  to  get  rid  of  the  irritant.  If  the  leg  is  held,  the  other 
is  brought  into  action.     Immerse  the  frog  in  water  to  wash  away  the  acid . 

(5)  Spread  {Irradiation)  of  Reflexes.— Gently  stimulate  a  toe  or  a  small 
spot  on  the  flank  with  weak  induction  shocks  or  weak  mechanical 
stimuli,  and  note  the  reflex  eftect  obtained.  Then  go  on  gradually 
increasing  the  strength  of  stimulation  without  increasing  the  area  of 
the  field  stimulated,  and  observe  the  extent  and  order  of  spread  of  the 
reflex  movements. 

3.  Reflex  Time. — Pass  a  hook  through  the  jaws.  Holding  the  frog  by 
the  hook,  dip  one  leg  into  a  dilute  solution  of  sulphuric  acid  (0-2  to 
o'5  per  cent.),  and  note  with  the  stop-watch  the  interval  which  elapses 
before  the  frog  draws  up  its  leg  (Tiirck's  method  of  determining  the 
reflex  time).     Wash  the  acid  off  with  water. 

Determine  how  the  reflex  time  varies  with  the  strength  of  the  stimulus. 
This  can  be  done  by  using  various  strengths  of  acid.  The  reflex  time 
will  be  shorter  the  stronger  the  stimulus  up  to  a  certain  point.  Compare 
the  reflex  time  of  movements  on  the  same  side  of  the  body  as  the  point 
of  application  of  the  stimulus  and  on  the  opposite  side. 


'   PRACTICAL  EXERCISES  959 

4.  Inhibition  of  the  Reflexes. — (i)  Destroy  the  cerebrum  of  a  frog. 
Dip  one  leg  into  dilute  sulphuric  acid  as  in  3,  and  estimate  the  reflex 
time.  Then  apply  a  crystal  of  common  salt  to  the  upper  part  of  the 
spinal  cord.  If  the  opening  made  for  pithing  the  frog  is  not  large  enough 
to  enable  the  cord  to  be  clearly  seen,  enlarge  it.  Again  dip  the  leg  in 
the  dilute  acid.  It  will  either  not  be  drawn  up  at  all,  or  the  interval  will 
be  distinctly  longer  than  before. 

(2)  Expose  the  viscera,  including  the  heart,  taking  care  not  to  injure 
the  cardiac  nerves.  Tap  the  intestines  sharply  with  the  handle  of  a 
scalpel  many  times  in  succession.     The  heart  is  inhibited. 

(3)  Tie  strings  tightly  around  both  fore-legs  of  a  normal  frog.  Place 
the  animal  on  its  back;  it  docs  not  turn  over.  The  hind-legs  may  be 
pulled  about  in  various  ways  without  the  frog  turning  over  into  its 
normal  position.  The  reactions  concerned  in  the  maintenance  of 
equilibrium  are  inhibited.  Remove  the  strings.  The  animal  cannot 
be  made  to  lie  on  its  back  except  by  force. 

5.  Spinal  Cord  and  Muscular  Tonus. — Destroy  the  brain  of  a  frog. 
Isolate  the  gastrocnemius,  and  cut  away  the  bone  below  the  knee. 
Isolate  the  sciatic  nerve  without  injuring  it.  Remove  the  muscles  from 
the  femur,  cut  the  bone  and  fix  it  in  a  clamp  for  graphic  recording. 
Connect  the  tendon  with  a  lever,  weighted  with  5  to  10  grammes.  Take 
a  base  line.  Destroy  the  spinal  cord,  or  cut  the  sciatic  and  again  take 
a  base  line.     TTie  length  of  the  muscle  is  slightly  altered. 

6.  Spinal  Cord  and  Tonus  of  the  Bloodvessels. — Destroy  the  brain  of 
a  frog.  Arrange  the  web  of  the  foot  on  the  stage  of  a  microscope,  and 
note  the  calibre  of  the  bloodvessels  in  the  field.  Destroy  the  cord,  and 
observe  the  change  in  their  calibre.     They  will  dilate. 

7.  Action  of  Strychnine. — Pith  a  frog  (brain  only).  Inject  into  one  of 
the  lymph-sacs  three  or  four  drops  of  a  ot  per  cent,  solution  of  strych- 
nine. In  a  few  minutes  general  spasms  come  on,  which  have  inter- 
missions, but  are  excited  by  the  slightest  stimulus.  The  extensor 
muscles  of  the  trunk  and  limbs  overcome  the  flexors.  Destroy  the 
spinal  cord;  the  spasms  at  once  cease,  and  cannot  again  hp  excited. 

8.  Mammalian  Spinal  Preparation  (Sherrington).* — Deeply  anaes- 
thetize a  cat  with  ether.  Insert  a  cannula  into  the  trachea  (p.  200),  and 
continue  the  anaGSthesia  through  this.  Expose  and  ligate  both  common 
carotids.  Make  a  transverse  incision  through  the  skin  over  the  occiput, 
and  extend  it  laterally  behind  the  ears.  Pull  back  the  skin  so  as  to 
expose  the  neck  muscles  at  the  level  of  the  axis  vertebra.  Feel  for  the 
ends  of  the  transverse  processes  of  the  atlas,  and  divide  the  muscles 
down  to  the  bone  just  behind  these  processes.  Now  start  artificial 
respiration  (p.  200),  or  sooner  if  necessary.  Notch  the  spinous  process 
of  the  axis  with  bone  forceps.  Pass  a  strong  thick  ligature  by  a  sharp- 
ended  aneurism  needle  close  under  the  body  of  the  axis,  and  tie  it  tightly 
in  the  groove  left  by  the  incision  behind  the  transverse  processes  of  the 
atlas  and  the  notch  made  in  the  spinous  process  of  the  axis.  This  com- 
presses the  vertebral  arteries  where  they  pass  from  transverse  process 
of  axis  to  transverse  process  of  atlas.     Pass  a  second  strong  ligature 

•  A  similar  preparation  can  be  used  for  certain  experiments  on  the  circu- 
lation (Crilc,  Guthrie).  For  these,  as  well  as  for  the  study  of  many  reflexes, 
a  good  preparation  is  obtained  by  occlu.sion  of  the  cerebral  blood-supply  in  cats 
(without  decapitation).  Even  a  human  'spinal  preparation'  is  capable  of 
executing  reflex  movements.  The  lurkomans  arc  statetl  to  have  decapitated 
their  prisoners  and  immediately  placed  on  the  neck  a  hot  metal  plate,  wh  ch 
seale<l  up  the  cut  vessels.  The  (reflex)  movements,  which  are  described  as  very 
lively,  were  then  watched  with  an  interest,  it  is  to  be  supposed,  not  wholly 
scientific. 


96o  THE  CENTRAL  NERVOUS  SYSTEM 

under  the  trachea  at  the  level  of  the  cricoid  cartilage  and  include  in  it 
the  whole  neck,  except  the  trachea,  but  at  present  only  tie  a  single  loop 
on  it.  Now  decapitate  the  animal  with  a  large  knife  (an  amputating 
knife)  passed  from  the  ventral  aspect  of  the  neck  through  the  occipito- 
atlantal  space,  severing  the  cord  just  behind  its  junction  with  the  bulb. 
At  the  moment  of  decapitation  tighten  the  ligature  round  the  neck  and 
complete  the  knot.  Destroy  the  head.  If  there  is  oozing  of  blood  from 
the  vertebral  canal,  arrest  it  by  raising  the  neck  somewhat  above  the 
level  of  the  body.  The  carcass  must  be  kept  warm  by  placing  it  on  a 
metal  box  or  table  containing  hot  water,  and  the  air  used  for  artificial 
respiration  must  also  be  warmed,  as  by  passing  it  through  a  coil  of 
rubber  tubing  immersed  in  a  water-bath  which  is  kept  hot.  Stitch  the 
skin-flaps  together  so  as  to  cover  the  cut  end  of  the  spinal  cord  and  the 
other  structures  cut  in  decapitation.  By  this  procedure  the  spinal  cord 
is  usually  severed  about  4  millimetres  behind  the  point  of  the  calamus 
scriptorius.  Although  the  blood-pressure  remains  low,  reflexes  employ- 
ing the  skeletal  museles  can  be  fairly  well  elicited  for  hours.  Study  on 
the  preparation  the  reflexes  described  in  the  text  (pp.  873,  876) — e.g.,  the 
flexion  reflex  of  the  hind  and  fore  limb,  as  elicited  from  the  skin,  or  one 
of  the  afferent  nerves  of  the  limb — the  crossed  extension  reflex  of  hind 
and  fore  limb,  the  scratch  reflex. 

(i)  Scratch  Reflex. — (a)  Evoke  the  reflex  by  rubbing  the  skin  of  the 
neck  behind  the  pinna.  The  scratching  movements  are  in  the  hind-leg 
of  the  same  side.  Record  them  on  a  drum,  on  which  is  also  written  a 
time-tracing  in  seconds.  The  record  can  be  obtained  by  tying  a  piece 
of  tape,  not  too  tightly,  round  the  foot,  leg,  or  thigh,  and  connecting 
this  by  a  thread  with  a  lever.  The  thread  is  passed  over  a  pulley  below 
the  lever,  so  that  its  pull  may  be  exerted  at  right  angles  to  the  axis  of 
rotation  of  the  lever.  The  lever  is  attached  to  a  light  spring  or  a  rubber 
band,  which  is  stretched  when  it  moves  in  one  direction,  and  in  recoiling 
brings  it  back  again  to  its  position  of  rest  at  the  end  of  the  contraction. 
If  the  reflex  is  not  easily  evoked,  it  can  be  facilitated  by  producing  a 
slight  degree  of  asphyxia  by  temporarily  clamping  the  respiration  tube. 
Some  time  must  elapse  after  the  decapitation  before  a  fair  scratch  reflex 
can  be  expected.     It  is  usually  sufficiently  well  marked  within  an  hour. 

(6)  While  the  reflex  is  occurring,  stimulate  with  an  interrupted  current 
the  central  stump  of  the  popliteal  nerve  of  the  opposite  hind-limb. 
The  scratch  reflex  may  be  cut  short  by  inhibition.  Also,  during  the 
stimulation  of  this  nerve  the  reflex  may  be  incapable  of  being  elicited 
till  the  excitation  of  the  inhibitory  afferen-toinerve  is  stopped. 

(2)  Flexion  Reflex. — (a)  Stimulate  with  a  weak  interrupted  current 
the  skin  of  some  part  of  the  hind -limb — say  one  of  the  toes.  The  flexion 
reflex  of  the  hind-limb  on  the  same  side  may  be  evoked — i.e.,  a  flexion 
movement  at  the  knee,  hip,  and  ankle.  Record  the  movements  of  one 
of  the  joints  or  of  flexor  muscles  after  severing  them  from  their  insertion. 

{b)  Stimulate  with  a  weak  interrupted  (faradic)  cvirrcnt  the  central 
stump  of  one  of  the  nerves  of  a  hind-limb — say  the  peroneal  nerve. 
The  flexion  reflex  of  the  same  limb  may  be  elicited.  Record  the  move- 
ments. Now  produce  temporaiy  asphyxia  by  clamping  the  respiration 
tube,  and  repeat  the  stimulation  at  ha  If -minute  intervals.  The  reflex 
will  be  increased  by  the  asphyxia.  Do  not  interrupt  the  respiration  for 
more  than  two  or  three  minutes,  and  immediately  start  it  if  the  heart, 
which  can  be  felt  through  the  chest,  begins  to  weaken. 

(3)  Elicit  the  knee-jerk,  as  described  in  the  text  (p.  876).  It  is 
generally  exaggerated. 

(4)  By  the  unipolar  method  (p.  gi8)  stimulate  with  a  point  electrode 
one  lateral  half  of  the  cross-section  of   the  cervical  cord  exposed  in 


PR  A  C  TIC  A  L  EXERCJ^  ES 


961 


decapitation.  The  large  electrode  is  placed  on  a  shaved  part  of  a  fore- 
arm. Various  effects  may  be  elicited  according  to  the  point  of  the  cross- 
section  stimulated — e.g.,  stepping  and  scratch  movcmenis  of  the  hind- 
limbs.  ()tii(  r  facts  mentioned  in  the  text  in  regard  to  spinal  reflexes  can 
be  verified  on  this  jjrcparalion. 

9.  Reflexes  in  Man.— Study  systematically  on  a  fellow-student  and 
on  yourself  tlic  i  liitf  reflexes  described  in  the  text  (p.  886),  especially — 

The  Knee-jerk. — (i)  Elicit  the  jerk  in  the  usual  way  by  striking  the 
ligament uin  palellrc  and  observe  its  height.     Then  cause  the  patient  to 
make  a  strong  voluntary  movement  (scpicczing  the  hands  together  or 
clenching  the  jaws)  at  the   moment  when   the 
tendon  is  struck,  and  note  whether  the  height  is 
increased  by  '  reinforcement.' 

(2)  Attach  a  suitable  recording  apparatus  to 
the  foot  of  a  person  sitting  with  his  legs  over  the 
edge  of  a  table,  and  record  the  jerks  elicited  by 
taps  made  as  uniform  in  strength  as  possible.  A 
small  hammer  worked  by  an  electro-magnet  or  a 
spring  might  be  employed  for  this  purjiose.  Com- 
pare the  records  obtained  when  the  jerk  is  elicited 
while  the  person  is  squeezing  his  hands  together 
with  those  previously  obtained.  The  influence  of 
mental  activity,  especially  of  excitement  or  irri- 
tation (opportunities  of  studying  such  psychical 
states  occasionally  offer  themselves  in  physio- 
logical laboratories)  in  increasing  the  height  of 
the  knee-jerk  mav  also  be  verified  (Lombard). 

10.  ExcisioD  of  Cerebral  Hemispheres  in  the 
Frog  (Fig.  383). — Ana-stlietize  a  frog  lightly  by 
puttingit  under  a  bell-jar  or  tumbler  with  a  small 
piece  of  cotton-wool  soaked  in  ether.  Put  very 
little  ether  on  the  cotton,  and  leave  the  frog  only 
a  very  short  time  under  the  bell-jar.  Then, 
holding  it  in  a  cloth,  make  an  incision  through 
the  skin  over  the  skull  in  the  mesial  line.  With 
scissors  open  the  cranium  about  the  position  of  a 
line  drawn  at  a  tangent  to  the  posterior  bonders 
of  the  two  tympanic  membranes.  Remove  the 
roof  of  the  skull  in  front  of  this  line  with  forceps, 
scoop  out  the  cerebral  hemispheres,  and  sew  up 
the  wound.  As  soon  as  the  animal  has  recovered 
from  the  ether,  the  phenomena  described  at 
p.  915  should  be  verified.  The  frog  will  swim 
when  thrown  into  water,  will  refuse  to  lie  on  its 

back,  and  will  not  fall  if  the  board  on  which  it  lies  be  gradually  slanted. 
Let  the  frog  live  for  a  day,  keeping  it  in  a  moist  atmosphere;  then 
expose  the  brain  again,  determine  the  reflex  time  by  Tiirck's  method; 
apply  a  crystal  of  common  salt  to  the  optic  lobes,  and  repeat  the  observa- 
tion. The  reflex  movements  will  bo  completely  inhibited  or  delayed. 
Remove  the  salt,  wa^h  with  physiological  salt  solution,  excise  the  optic 
lobes,  and  see  whether  the  frog  will  now  swim. 

II.  Excision  of  the  Cerebral  Hemispheres  in  a  Pigeon.— Feed  a  pigeon 
for  two  or  three  davs  on  drv  food,  etherize  it  l>y  iiokling  a  piece  »  t 
cotton-wool  spriiilded  with  etiier  over  its  l>eak.  or  inject  into  the  rectum 
ij  gramme  i  liloial  iivdrate.  The  jiigeon  being  wrapped  up  in  a  cloth, 
and  the  head  held  steady  by  an  assistant .  the  feathers  areclipped  off  the 

61 


Fig-  383. —  Brain  of  Frog 
(after  SteiiuT).  a.cere- 
bral  hemispheres;  b, 
position  of  optic  thala- 
mi;  c,  optic  lobes;  d, 
cerebellum ;  e.  medulla 
olilongata;  A,  upper 
end  of  spinal  cord. 


962  THE  CENTRAL  NERVOUS  SYSTEM 

head,  an  incision  made  in  the  middle  line  through  the  skin,  and  the  flaps 
reflected  so  as  to  expose  the  skull.  Cut  through  the  bones  with  scissors, 
and  make  a  sufficiently  large  opening  to  bring  the  cerebral  hemispheres 
into  view.  They  are  now  rapidly  divided  from  the  corpora  bigemina 
and  lifted  out  with  the  handle  of  a  scalpel.  The  bleeding  is  very  free,  but 
may  be  partially  controlled  by  stuffing  the  cavity  with  the  vegetable 
fibre  known  as  Pengavar  Djambi,  which  should  be  removed  in  a  few 
minutes,  the  wound  cleansed  with  iodoform  gauze  wrung  out  of  physio- 
logical salt  solution  at  50'  C,  and  sewed  up.  Study  the  phenomena 
described  on  p.  915. 

12.  Stimulation  of  the  Motor  Areas  in  the  Dog. — {a)  Study  a  hardened 
brain  of  a  dog,  noting  especially  the  crucial  sulcus  (Fig.  367.  p.  917),  the 
convolutions  in  relation  to  it,  and  the  areas  mapped  out  around  it  by 
Hitzig  and  Fritsch  and  others,     [b)  Inject  morphine  under  the  skin  of 
a  dog.     Set  up  an  induction-coil  arranged  for  tetanus,  with  a  single 
Daniell  in  the  primary  circuit.     Connect  a  pair  of  fine  but  not  sharp- 
pointed  electrodes  through  a  short-circuiting  key  with  the  secondary. 
Fasten  the  dog  on  the  holder,  belly  down,  and  put  a  large  pad  under  the 
neck  to  support  the  head.     Clip  the  hair  over  the  scalp.     Feel  for  the 
condyles  of  the  lower  jaw,  and  join  them  by  a  string  across  the  top  of  the 
head.     Connect  the  outer  canthi  of  the  eyes  by  another  thread.     The 
crucial  sulcus  lies  a  little  behind  the  mid-point  between  these  two  lines. 
Now  give  the  dog  ether,  make  a  mesial  incision  through  the  skin  down 
to  the  bone,  and  reflect  the  flaps  on  either  side.     Detach  as  much  of  the 
temporal  muscle  from  the  bone  as  is  necessary  to  get  room  for  two 
trephine  holes,  the  internal  borders  of  which  must  be  not  less  than 
J  inch  from  the  middle  line,  so  as  to  avoid  wounding  the  longitudinal 
sinus.     Carefully  work  the  trephine  through  the  skull,  taking  care  not 
to  press  heavily  on  it  at  the  last.     Raise  up  the  two  pieces  of  bone  with 
forceps,  connect  the  holes  with  bone  forceps,  and  enlarge  the  opening  as 
much  as  may  be  necessary  to  reach  all  the  '  motor '  areas.     At  this 
.    stage  only  enough  ether  should  be  given  to  prevent  suffering.     Now 
unbind  the  hind-  and  fore-limbs  on  the  side  opposite  to  that  on  which 
the  brain  has  been  exposed,  apply  blunt  electrodes  successively  to  the 
areas  for  the  fore-  and  hind-limbs,  and  stimulate.*     The  'unipolar' 
method  of  stimulation  (p.  918)  may  also  be  employed.     Contraction  of 
the  corresponding  groups  of  muscles  will  be  seen  if  the  narcosis  is  not 
too  deep.     Movements  of  the  head,  neck,  and  eyelids  may  also  be  called 
forth  by  stimulating  the  '  motor  '  areas  for  these  regions.     Stimulation 
in  front  of  the  crucial  sulcus  may  also  cause  great  dilatation  of  the  pupil, 
the  iris  almost  disappearing.     The  dilatation  takes  place  most  promptly 
and  is  greatest  on  the  opposite  side,  but  the  pupil  on  the  same  side  is 
also  widened.     Even  after  section  of  both  vago-sympathetic  nerves  in 
the  neck,  a  slow  and  slight  dilatation,  greatest  perhaps  on  the  same  side, 
may  be  caused  by  cortical  stimulation.     Repeat  the  whole  experiment 
on  the  opposite  side  of  the  brain.     In  the  course  of  his  observations  the 
student  will  perhaps  have  the  opportunity  of  seeing  general  epileptiform 
convulsions  set  up  by  a  localized  excitation.     They  begin  in  the  group 
of  muscles  represented  in  the  portion  of  the  cortex  directly  stimulated. 
After  the  convulsions  have  been  sufficiently  studied,  they  should  be 
again  induced,  and  the  stimulated  '  motor  '  area  rapidly  excised  during 
their  course.     In  some  cases  this  will  be  followed  by  immediate  cessation 
of  the  spasms,      (c)  The  same  animal  can  be  used  for  stimulation  of  the 
spinal  nerve-roots,  as  described  in  Experiment  i  (p.  957). 

*  It  is  not  necessary  to  remove  the  dura  mater. 


CHAPTER  XVII 

THE  AUTONOMIC  NERVOUS  SYSTEM  (THE   SYMPATHETIC 
AND  ALLIED  NERVES) 

The  efferent  fibres  of  the  body  can  be  divided  into  two  classes, 
(i)  Those  which  supply  multinuclear  striated  muscle  (skeletal 
muscle) ;  (2)  those  which  supply  other  structures  (smooth  muscle, 
heart  muscle,  glands).  The  second  group  is  called  '  autonomic,' 
to  indicate  that  it  possesses  a  certain  independence  of  the  central 
nervous  system,  although  this  independence  is  far  from  absolute. 
The  autonomic  fibres  arise  from  four  regions  of  the  central  nervous 
system  :  (i)  The  mid-brain;  (2)  the  bulb;  (3)  the  thoracic  and  upper 
lumbar  cord;  (4)  the  sacral  portion  of  the  cord.  AH  autonomic 
fibres  after  issuing  from  the  central  nervous  system  end  sooner  or 
later  by  forming  synapses  around  nerve-cells  of  sympathetic  type, 
by  whose  axons  the  path  is  continued  to  the  peripheral  distribution. 
The  autonomic  path  accordingly  comprises  two  neurons,  the  fibre 
which  arises  from  the  brain  or  cord  being  termed  the  '  pregang- 
lionic,' and  that  which  arises  from  the  sympathetic  ganglion  the 
'  postganglionic  '  fibre. 

The  autonomic  fibres  originating  in  the  mid-brain  emerge  in  the 
oculo-motor  nerve,  and  form  synapses  with  cells  in  the  ciliary 
ganglion,  which  in  turn  send  fibres  to  the  ciliary  muscle  and  the 
constrictor  muscle  of  the  iris  (pp.  894,  984).  The  bulbar  autonomic 
fibres  emerge  in  the  seventh,  ninth,  and  tenth  cranial  nerves.  Those 
in  the  vagus  include  inhibitory  fibrt-s  for  the  heart  muscle,  motor  and 
inhibitory  fibres  for  the  smooth  muscle  of  the  alimentary  canal  from 
the  oesophagus  to  the  descending  colon,  and  for  the  muscles  of  the 
trachea  and  lungs,  and  secretory  fibres  for  the  gastric  glands  and 
the  pancreas.  The  sympathetic  ganglion  cells  with  which  these 
preganglionic  fibres  form  synapses  have  not  always  been  definitely 
located,  but  lie  near  or  in  the  tissue  supplied  (p.  179).  The  auto- 
nomic fibres  in  the  seventh  and  ninth  nervi-s  supply  the  mucous 
membranes  of  the  mouth  and  nose  with  vaso-dilator  and  secu'tory 
fibres.  The  preganglionic  portion  of  the  path  ttrminates  in  such 
ganglia  as  the  submaxillary  and  sublingual  (p.  385)  and  the  spheno- 
palatine and  otic  ganglia. 

963 


964 


THE  AUTONOMIC  NERVOUS  SYSTEM 


The  part  of  the  autonomic  system  which  originates  in  the  middle 
region  of  the  spinal  cord  (in  the  cat  from  the  first  thoracic  to  the 
fourth  or  fifth  lumbar  nerves)  is  the  sympathetic  proper.  The 
course  of  the  fibres  has  already  been  described  in  connection  with 
the  vaso-motor  nerves  (p.  179).  Among  the  fibres  may  be  men- 
tioned the  dilators  of  the  pupil,  the  augment ors 
of  the  heart,  motor  (viscero-motor)  and  inhibi- 
tory fibres  for  the  smooth  muscle  of  the  alimen- 
tar}'  canal,  sweat-secretory,  pilo-motor  and  vaso- 
constrictor fibres.  The  preganglionic  fibres  issue 
from  the  cord  in  the  anterior  roots,  and  leave 
the  corresponding  spinal  nerve  in  the  white 
ramus  commimicans,  which  connects  it  with  the 
corresponding  ganglion  of  the  lateral  sympa- 
thetic chain.  A  fibre  may  either  end  in  this 
ganglion  by  forming  a  synapse,  or  it  may  run  up 
or  down  in  the  chain  for  some  distance  before 
terminating.  Some  of  the  preganglionic  fibres, 
particularly  the  vaso-constrictors  for  the  ab- 
dominal and  pelvic  viscera,  do  not  end  in  the 
lateral  chain  at  all,  but,  issuing  from  it  still  as 
medullated  fibres,  terminate  in  one  of  the  pre- 
vertebral ganglia — i.g.,  coeliac  ganglion,  inferior 
mesenteric  ganghon — from  which  postganglionic 
fibres  proceed  to  the  viscera,  as  previously 
described  (p.  326).  The  postganglionic  fibres 
arising  from  cells  of  the  lateral  ganglia  return 
as  non-medullated  fibres  in  grey  rami  com- 
municating to  the  spinal  nerves,  and  are  dis- 
tributed \\dth  them  to  the  head,  limbs,  and  the 
superficial  parts  of  the  trunk. 

The  autonomic  fibres  arising  from  the  sacral 
region  of  the  cord  emerge  as  preganglionic  fibres 
in  the  anterior  roots  of  the  second  to  the  fourth 
sacral  nerves,  from  which  they  pass  to  the  pelvic 
nerve  (nervus  erigens)  (pp.  179,  326).  They 
comprise  vaso-dilator  fibres  for  the  rectum,  anus, 
and  external  genitals,  motor  (viscero-motor) 
fibres  for  the  smooth  muscle  of  the  descending 
colon,  rectum,  and  anus,  inhibitory  fibres  for 
the  smooth  muscle  of  the  anus,  and  the 
muscles  of  the  external  genitals,  motor  fibres  for  the  bladder,  etc. 
The  preganglionic  fibres  terminate  by  forming  synapses  with 
sympathetic  ganghon  cells  in  the  pelvic  plexus,  or  in  the  neighbour- 
hood of  the  organs  which  they  supply.  From  these  ganglion  cells 
the  postganglionic  fibres  arise. 


1           \M?e/- 
\       JBratn 

Msulb 

1 

0 

13 
% 

•4 

Sdcral. 

Fig.   38 
showi 
tral   ( 
Autoi 
(Lang 

4.  —  Diagram 
ng    the    Cen- 
Drigin   of   the 
lomic     Fibres 
ley). 

FUNCTIONS  OF  THE  AUTONOMIC  SYSTEM  965 

Action  of  Nicotin  and  Adrenalin  on  the  Autonomic  System. — 
The  action  of  nicotin  upon  tlir"  synii)ath«-tic  {^angHon  it-lls,  or  the 
hnk  between  them  and  the  preganglionic  libres,  which  has  been 
taken  advantage  of  in  tracing  the  course  of  the  autonomic  libres, 
has  already  been  described  (p.  180).  The  special  relation  ol  adrena- 
lin or  epincphrin  to  the  sympathetic,  although  not  to  the  rest  of  the 
autonomic  system,  has  also  been  alluded  to  (p.  63S). 

Functions  of  the  Autonomic  System. — Thi-  functions  of  the  auto- 
nomic nerves  are  sulluicnt ly  delined  by  the  enumeration  f)f  the 
peripheral  organs  with  which  they  are  connected.  It  is  obvious 
that  they  preside  over  functions  for  the  most  part  withdrawn  from 
the  control  of  the  will,  the  so-called  vegetative  functions,  like  the 
heart-beat,  the  tone  of  the  bloodvessels,  the  movements  of  the 
alimentary  canal  and  of  the  uterus,  the  erection  of  the  hairs,  and 
the  secretion  of  sweat.  It  is  no  doubt  advantageous  that  these 
functions  should  be  withdrawn  from  voluntary  control,  and  this 
withdrawal  is,  we  may  assume,  secured  either  by  the  absence  of 
anatomical  connections  between  the  regions  of  the  cortex  connected 
with  voluntary  movements  and  the  ganglion  cells  in  the  cerebro- 
spinal axis  from  which  the  preganglionic  fibres  arise,  or  by  the 
existence  of  a  high  threshold  of  resistance  in  such  paths  as  exist. 
There  is  no  anatomical  or  physiological  reason  why  autonomic 
fibres  should  not  carry  impulses  which  would  elicit  voluntary  move- 
ments were  such  impulses  once  shunted  on  to  an  autonomic  path, 
and  certain  autonomic  fibres  do  innervate  structures  which  are 
under  voluntary  control — e.g.,  the  fibres  to  the  ciliary  muscle  of 
the  eye  and  those  to  the  urinary  bladder.  The  power  of  voluntarily 
accelerating  the  heart  possessed  by  some  individuals  (p.  170)  is 
a  further  instance  showing  that  the  general  rule  is  broken  by  ex- 
ceptions. 


CHAPTER  XVIII 
THE  SENSES 

Hitherto  we  have  been  considering  from  a  purely  objective  standpoint 
the  organs  that  compose  the  body,  and  their  work.  The  student  has 
been  assumed  to  be  in  the  little  world — the  '  microcosm  ' — of  organiza- 
tion which  he  has  been  studying,  but  not  of  it.  He  has  listened  to  the 
sounds  of  the  heart,  seen  its  contraction,  felt  it  hardening  under  his 
fingers ;  but  we  have  not  inquired  as  to  the  meaning  or  the  mechanism 
of  this  hearing,  seeing,  and  feeling.  We  have  now  to  recognize  that  all 
our  knowledge  of  external  things  comes  to  us  by  the  channels  of  the 
senses,  and,  like  the  light  that  falls  through  coloured  windows  on  the  floor 
of  a  church,  is  tinged,  and  perhaps  distorted,  in  the  act  of  reaching  us. 

The  Senses  in  General. — The  old  and  orthodox  enumeration  of 
'  the  five  senses  '  of  sight,  hearing,  touch,  taste,  and  smell,  must 
be  augmented  by  at  least  two  more,  the  senses  of  pressure  and 
temperature.  The  so-called  temperature  sensations  are  themselves 
divisible  into  two  groups  of  quite  distinctive  quality,  sensations  of 
warmth  and  sensations  of  cold.  The  power  of  appreciating  the 
amount  of  a  muscular  effort;  the  power  of  localizing  the  various 
portions  of  the  body  in  space ;  the  sensations  of  pain,  tickling,  itching, 
hunger,  and  thirst;  the  sensations  accompanying  the  generative 
act,  etc.,  can  certainly  be  no  longer  lumped  together  in  the  omnium 
gatherum  of  'common  sensibility.'  They  are  more  appropriately 
regarded  as  separate  senses  subserved  by  special  nerves,  and 
perhaps  connected  with  definite  centres.  In  the  development  of 
a  simple  sensation  we  may  distinguish  three  stages:  the  stimulation 
of  a  peripheral  end-organ,  the  propagation  of  the  impulses  thus  set 
UD  along  an  afferent  nerve,  and  their  reception  and  elaboration  in 
a  central  organ. 

We  do  not  know  in  what  manner  a  series  of  transverse  vibrations  in 
the  ether  when  it  falls  upon  the  eye,  or  a  series  of  longitudinal  vibrations 
in  the  air  when  it  strikes  the  ear,  excites  a  sensation  of  light  or  sound. 
We  can  trace  the  ray  of  light  through  the  refractive  media  of  the  eyeball, 
see  it  focussed  on  the  retina,  lead  off  the  current  of  action  set  up  in  that 
membrane,  which,  doubtless,  gives  token  of  the  passage  of  nervous 
impulses  into  and  up  the  optic  nerve.  We  can  even  follow  the  nervous 
impulses  to  a  definite  portion  of  the  cortex  of  the  occipital  lobe,  and 
determine  that  if  this  is  removed  no  sensation  of  .sight  will  result  from 

966 


THE  SENSES  IN  GENERAL  907 

any  excitation  of  retina  or  optic  nerve.  And  it  is  fair  to  conclude  that 
in  some  manner  this  part  of  the  cerebral  cortex  is  essential  to  the  pro- 
duction of  visual  sensations.  But  in  what  way  the  chemi(  al  or  physical 
processes  in  the  axis-cylinders  or  nerve-cells  are  related  to  the  |)sychical 
change,  the  interruption  of  the  smooth  and  unregarded  flow  of  conscious- 
ness which  we  call  a  sensation  of  light,  we  do  not  know.  To  our 
reasoning,  and  even  to  our  imagination,  there  is  a  great  gulf  fixed  between 
the  physical  stimulus  and  its  psychical  consequence;  they  seem  incom- 
mensurable quantities;  the  transition  from  light  to  sensation  of  light  is 
certain,  but  unthinkable. 

Each  kind  of  peripheral  end-organ  is  jxjcuharly  suited  to  respond 
to  a  certain  kind  of  stimulus.  The  law  of  'adequate  '  or  '  homol- 
ogous '  stimuli  is  an  expression  of  this  fact.  The  '  adequate  ' 
stimuli  of  the  organs  of  special  sense  may  be  divided  into  (i)  vibra- 
tions set  up  at  a  distance  without  the  actual  contact  of  the  object 
— e.g.,  light,  sound,  radiant  heat;  (2)  changes  produced  by  the 
contact  of  the  object — e.g.,  in  the  production  of  sensations  of  taste, 
touch,  pressure,  alteration  of  temperature  (by  conduction).  Mid- 
way between  (i)  and,  (2)  lies  the  adequate  stimulus  of  the  olfactory 
end-organs,  which  are  c.xciled  by  material  particles  given  off  from 
the  odoriferous  body  and  borne  by  the  air  into  the  upper  part  of 
the  nostrils. 

The  end-organs  of  the  special  senses  all  agree  in  consisting  essentially 
of  modified  ectodermic  cells,  but  they  occupy  areas  by  no  means  pro- 
portioned to  their  importance  and  to  the  amount  of  information  we 
acquire  through  them.  The  extent  of  surface  which  can  be  affected  by 
light  in  a  man  is  not  more  than  20  sq.  cm. ;  the  endings  of  both  nerves  of 
hearing  taken  together  do  not  at  most  expand  to  more  than  5  sq.  cm.; 
the  olfactory  portion  of  the  mucous  membrane  of  the  nose  has  an  area  of 
not  more  than  10  sq.  cm.;  the  sensations  of  taste  are  ministered  to  by 
an  area  of  less  than  50  sq.  cm. ;  the  end-organs  of  the  senses  of  pressure, 
touch,  and  temperature  are  distributed  over  a  surface  reckoned  by 
square  metres.  As  the  i)hysiological  status  of  the  sensory  end-organs 
rises,  their  anatomical  distribution  tends  to  shrink.  The  organs  of  com- 
paratively coarse  and  common  sensations  are  widely  spread,  inter- 
mingled with  each  other,  and  seated  in  tissues  whose  primary  function 
may  not  be  sensory  at  all.  Even  the  nerve-endings  of  the  sense  of  taste 
are  not  confined  to  one  definite  and  circumscribed  patch,  but  scattered 
over  the  tongue  and  palate ;  and  both  tongue  and  palate  are  at  least  as 
much  concerned  in  mastication  and  deglutition  as  in  taste.  The 
olfactory  portion  of  the  nasal  mucous  membrane,  although  a  continuous 
area  with  fairly  distinct  boundaries,  is  still  a  part  of  the  general  lining 
of  the  nostril.  The  ejiithelial  surfaces  which  minister  to  the  supreme 
sensations  of  sight  and  hearing — the  retina  and  the  sensitive  structures 
of  the  cochlea — are  the  most  sequestered  of  all  the  sensory  areas,  as  the 
organs  of  which  they  form  a  part  are,  of  all  the  organs  of  sense,  the  most 
highly  specialized  in  function,  and  anatomically  the  most  limited.  But 
although  hidden  in  protected  hollows,  they  arc  endowexl.  either  in  virtue 
of  their  own  movements  or  of  those  of  the  head,  with  the  power  of 
receiving  impressions  from  every  side,  and  their  actual  size  is  thus  in- 
definitely multiplied. 


968 


THE  SENSES 


Section  I. — Vision. 

Physical  Introduction. — Physically,  a  ray  of  light  is  a  series  of  dis- 
turbances or  vibrations  in  the  luminiferous  ether.  M'hich  radiates  out 
from  a  luminous  body  in  what  is  practically  a  straight  line.  The  ether 
is  supposed  to  fill  all  space,  inch  ding  Il:e  interstices  between  the  mole- 
cules of  matter  and  the  atoms  of  which  those  molecules  are  composed. 
Suppose  a  bar  of  iron  to  be  gradually  heated  in  a  dark  room.  In  the 
cold  iron  the  molecules  are  moving  on  the  average  at  a  relatively  slow 
rate,  and  the  waves  set  up  in  the  ether  by  their  vibrations  are  compara- 
tively long.  Now,  the  long  ethereal  vibrations  do  not  excite  the  retina, 
because  it  is  only  fitted  to  respond  to  the  impact  of  the  shorter  waves; 
and,  indeed,  the  long  waves  are  largely  absorbed  by  the  v/atery  media 
of  tiie  eye.  As  the  temperature  of  the  iron  bar  is  increased,  the  mole- 
cules begin  to  move  more  quickly,  and  waves  of  smaller  and  smaller 
length,  of  greater  and  greater  frequency,  are  set  up,  until  at  last  some 
of  thein  are  just  able  to  stimulate  the  retina,  and  the  iron  begins  to  glow 
a  dull  red.  As  the  heating  goes  on  the  molecules  move  more  quickly 
still,  and,  in  addition  to  waves  which  cause  the  sensation  of  red,  shorter 
waves  that  give  the  sensation  of  yellow  appear.  Finally,  when  a  high 
temperature  has  been  reached,  the  very  shortest  vibrations  which  can 

affect  the  eye  at  all  mingle  with  the  medium 
and  long  waves,  and  the  sensation  is  one  of 
intense  white  light. 

We  liave  said  that  a  ray  of  light  travels 
in  a  straight  line,  and  the  direction  of  the 
straight  line  does  not  change  as  long  as  the 
medium  is  homogeneous.  But  when  a  ray 
reaches  the  boundary  of  the  medium  through 
which  it  is  passing,  a  part  of  it  is  in  general 
turned  back  or  reflected.  If  the  second 
nfrdium  is  transparent  (water  or  glass,  e.g.), 
the  greater  part  of  the  ray  passes  on  through 
it,  a  smaller  portion  is  reflected.  If  the 
second  medium  is  opaque,  the  ray  does  not 
penetrate  it  for  any  great  distance;  if  it  is 
a  piece  of  polished  metal,  e.g.,  nearly  the 
whole  of  the  light  is  reflected ;  if  it  is  a  layer  of  lampblack,  very  little 
of  the  light  is  reflected,  most  of  it  is  absorbed. 

Reflection. — The  first  law  of  reflection  is  that  the  reflected  ray,  the  ray 
which  falls  upon  the  reflecting  surface  {incident  ray),  and  the  normal  to  the 
surface,  arc  in  one  plane.  The  second  law  is  that  the  reflected  ray  maJ.es 
with  the  perpendicular  (normal)  to  the  reflecting  surface  the  same  angle 
as  the  incident  ray.  A  corollary  to  this  is  that  a  ray  perpendicular  to 
the  surface  is  reflected  along  its  own  path. 

Reflection  from  a  Plane  Mirror. — Let  a  ray  of  light  coming  from  the 
point  P  (Fig.  385)  meet  the  surface  DE  at  B,  making  an  angle  PBA  with 
the  normal  to  the  surface.  The  reflected  ray  BC  will  make  an  equal 
angle  ABC  with  the  normal;  and  the  eye  at  C  will  see  the  image  of  P 
as  if  it  were  placed  at  P',  the  point  where  the  prolongation  of  BC  cuts 
the  straight  line  drawn  from  P  perpendicular  to  DE.  This  is  the  posi- 
tion of  an  ordinary  looking-glass  image. 

Reflection  from  a  Concave  Spherical  Mirror. — A  spherical  surface  may 
be  supposed  to  be  made  up  of  an  infinite  number  of  infinitely  small  plane 
surfaces.  The  normal  to  each  of  tlr  re  plane  surfaces  is  tlie  radius  of 
the  sphere,  and  the  reflected  ray  makes  with  the  radius  at  the  point  of 


Fig-   385. — Keflectiou    from 
Plane  Mirror. 


VISION 


969 


incidence  tlic  same  angle  as  the  incident  ray.  Lot  D  (Fig.  386)  be  the 
middle  p  )iiit  of  the  mirror,  and  C  its  centre  of  curvature — i.e.,  the 
centre  of  tlie  .spjiere  of  which  it  is  a  segment.  Then  CD  is  the  principal 
axis,  and  any  other  line  through  C  which  cuts  the  mirror  is  a  secondary 
axis.  When  the  mirror  is  a  small  portion  of  a  splierc,  rays  parallel  to 
the  priiiriixd  axis  are  focusscd  at  the  principal  focus  F  midway  between 
CandD;  rays  parall  1  to  any  secondary  axis  are  focusscd  in  a  p'^nt 


386. — Reflection    trom 
Soherical  Mirror. 


1""'-;     j"*7.  — For  nitiin    of   Real   Inverted 
Image  by  a  Concave  Spherical  Mirror. 


lying  on  that  axis;  and  rays  diverging  from  a  point  on  any  axis  are 
focusscd  in  a  point  on  the  same  axis. 

These  facts  afford  a  simple  construction  for  finding  the  position  of 
the  image  of  an  object  formed  by  a  concave  mirror.  Let  AB  be  the 
object  (Fig.  387).  Jhcn  the  image  of  A  is  the  point  in  which  all  rays 
proceeding  from  A  and  falling  on  the  mirror,  including  rays  parallel  to 
the  principal  axis,  are  focusscd.  But  the  ray  AE,  parallel  to  the  })rin- 
cipal  axis,  passes  after  reflection  through  tlie  principal  focus  F,  there- 
fore the  image  of  A  must  lie  on  the  straight  line  EF.  If  any  sccondar}' 
axis  ACD  be  drawn,  the 
image  of  A  must  lie  on 
ACD.  It  must  therefore 
be  the  point  of  intcrsi-c- 
tion,  a,  of  EF  and  ACD. 
Similarly,  the  image  of  B 
must  be  tlie  point  oif  inter- 
section, b,  of  GF  and  BCil. 
The  image  ab  of  an  object 
AB  farther  from  the  mirror 
than  the  principal  focus 
is  real  and  inverted.  Tlu' 
Purkinjc-Sanson  image  re- 
flected from  the  conca^'e 
anterior  surface  of  the 
vitreous  humour  (Fig.  402) 
is  an  example. 

After  re/lection  from  a  convex  mirror,  rays  of  light  alwa>'S  ,divcrgc.  and 
only  erect,  virtual  images  are  formed — i.e..  images  which  do  not  really 
exist  in  space,  but  which,  from  the  direction  of  the  rays  of  li^ht,  we,  judge 
to  exist.  The  jwsition  of  the  image  of  an  object  AB  (Fig.  3S8)  may  l>e 
found  by  a  construction  similar  to  that  for  reflection  from  a  concave 
mirror.  The  image  of  a  flame  rcflccte<l  from  the  anteriorsurface  of  the 
cornea  or  lens  is  erect  and  virtual.  It  diminishes  in  size  with  incrciisc 
in  the  curvature  or  convexity  of  the  reflecting  surface  (Fig.  402). 

Refraction. — A  ray  of  light  passing  from  one  medium  into  another 
has  its  velocity,  and  consequently  its  direction,  altered.     It  is  said  to 


Fig.  388. — Foriuatioa  of  Image  by  a  Conve.x  Mirror, 


970 


THE  SENSES 


be  refracted.  The  first  law  of  refraction  is  that  the  refracted  ray  is  in 
the  same  plane  as  the  incident  ray  and  the  normal  to  the  surface.  The 
second  law  is  that  the  sine  of  the  angle  of  incidence  has  a  constant  ratio 
(for  any  given  pair  of  media)  to  the  sine  of  the  angle  of  refraction.  The 
angle  of  incidence  is  the  angle  which  the  ray  makes  with  the  normal 
to  the  surface,  separating  the  two  media;  the  angle  of  refraction  is  the 
angle  made  with  the  normal  in  the  second  medium.  This  ratio  is  called 
the  index  of  refraction  between  the  two  media.  For  purposes  of  com- 
parison, the  refractive  index  of  a  substance  is  usunlly  taken  as  the  ratio 
of  the  sine  of  the  angle  of  incidence  to  the  sine  of  the  angle  of  refraction 
of  a  ray  passing  from  air  into  the  substance. 

When  a  ray  strikes  a  surface  at  right  angles,  it  passes  through  without 
suffering  refraction.  When  a  ray  pa  ses  from  a  less  dense  to  a  denser 
medium  [e.g.,  from  air  to  water),  it  i>  bent  towards  the  perpendicular. 


Fig.  389. — Refraction  at  a  Plane  Surface. 

AB  is  the  incident;  BD.  the  refracted 

ray;  CB,  the  normal   to  the  surface. 

When    the   ray   passes    from    air   into 

another  medium,  the  refractive  index  of 

,      ,       , .       sin  a 
the  latter  is  the  fraction  -^ — ;;-. 
sui  ^ 


Fig.  390. —  Refraction  by  a  Medium 
bounded  by  Parallel  Planes,  P  and 
P'.  The  ray  ABDE  issues  parallel 
to  its  original  direction;  CB,  FD, 
normals  to  P  and  P';  a,  angle  of 
incidence;  3, 7,  angles  of  refraction. 


When  it  passes  from  a  more  dense  to  a  less  dense  medium  (as  from 
water  to  air),  it  is  bent  away  from  the  perpendicular. 

When  a  ray  passes  across  a  medium  bounded  by  parallel  planes,  it 
issues  parallel  to  itself;  in  other  words,  it  undergoes  no  refraction 
(Fig.  390). 

Refraction  and  Dispersion  by  a  Prism. — The  beam  of  light  is  bent 
towards  the  normal  N  as  it  passes  across  BA  and  away  from  the  normal 
N'  as  it  passes  across  BC  (Fig.  391) ;  at  both  surfaces  it  is  bent  towards 
the  base  of  the  prism  AC.  At  the  same  time  the  light  suffers  dispersion 
— that  is,  the  rays  of  shorter  wave-length  are  more  refracted  than  those 
of  greater  wave-length.  The  deviation  of  any  given  ray  is  measured  by 
the  angle  which  the  refracted  ray  makes  with  its  original  direction. 
The  amount  of  dispersion  produced  by  a  prism  is  measured  by  the 
difference  in  the  deviation  of  the  extreme  rays  of  the  spectrum.  The 
dispersion  produced  by  a  given  substance  is  proportional  to  the  differ- 
ence of  its  refractive  indices  for  the  extreme  rays. 

Refraction  by  a  Biconvex  Lens. — A  straight  line  ABC  passing  through 
the  centres  of  curvature  of  the  two  surf;i<rs  of  the  lens  is  c.'lled  the 
principal  axis.      A  point  C  lying  on  the  principal  axis  between  the 


VISION 


971 


two  centres  of  curvature,  and  possessing  tlie  property  that  rays  passing 
through  it  do  not  suHcr  refraction,  is  callcrl  the  optical  centre  of  the 
lens.     Any  straight  line,  D("E,  passing  through  the  oi)tical  centre,  is  a 
secondary  axis.     Rays  of  liglit  proceeding  from  a  point  in  the  principal 
axis  are  focussed  in  a  point  on  that  axis.     When  the  rays  proceed  from 
an  infinitely  distant  point  in  the  principal  axis — i.e.,  when  they  are 
parallel  to  it — they  arc  focussed  in   F,   the  principal  focus.     Smilarly 
rays    jiarallel   to,    (  r 
proceeding    from,    a 
point  in  a  secondary 
axis  are  focussed  in 
a  point  on  that  axis ; 
but  if  the  focus  is  to 
be  sharp,  the  angle 
between   the    secon- 
dary and  the  princi- 
pal axis  must  not  be 
so    large   as  is  indi- 
cated in  Fig.  392. 

Formation  of  Im- 
age by  Biconvex  Lens 
(Fig.  393).— Let  AB 
be  the  object;  then 
if  AUD  be  the  path 
of  a  ray  from  A  parallel  to  the  principal  axis,  the  image  of  A  will  be  the 
intersection  of  the  straight  line  DF  and  the  secondary  axis  passing 
through  A.  Similarly,  the  image  of  B  will  be  the  intersection  of  GF" 
and  the  secondary  axis  BC.  Where  AB  is  farther  from  the  lens  than  4^ 
the  principal  focus,  the  image  ab  is  real  and  inverted.  This  is  the  case 
with  the  image  of  ;-,n  external  object  formed  on  the  retina.  W  hen  the 
object  is  nearer  than  tho  principal  focus,  the  image  is  virtual  and  direct. 


rig.  391.  — Rctiaction  and  Dispersion  by  a  Prism. 


39^. —  Refraction 
Biconvex  Lens. 


—  Formation    of 
Biconvex  Lens. 


The  image  formed  by  the  objective  of  a  microscope  when  the  object  is  in 
focus  is  real  and  inverted:  the  ocular  forms  a  virtual  erect  image  of  this 
real  image. 

Refraction  by  a  Biconcave  Lens  (Fig.  394). — Parallel  rays  are  rendered 
divergent  by  the  lens;  there  is  no  real  focus;  but  if  the  raj's  are  pro- 
longed backwards  they  meet  in  the  virtual  focus  F,  from  which  they 
appear  to  come  when  received  l>y  the  eve  through  the  lens. 

Formation  of  Image  by  Biconcave  Lens  (Fig.  395). — Ixt  AB  be  the 
object.     Let  AUDI  be  the  path  of  a  ray  from  any  point  A  of  the  object 


972 


THE  SENSES 


parallel  to  the  principal  axis.  Produce  DI  backwards  (dotted  line); 
it  will  pass  through  the  principal  focus  F.  Through  A  draw  the  second- 
ary axis  AC.  The  image  of  A  must  lie  both  on  AC  and  on  IDF — i.e., 
it  must  be  the  intersection,  a,  of  these  straight  lines.  Similarly,  the 
image  of  B  is  6,  the  intersection  of  KGF  and  BC.  The  image  is  virtual 
and  erect. 

Absorption. — No  substance  is  perfectly  transparent;  in  addition  to 
what  is  reflected,  some  li^ht  is  always  absorbed.     In  other  words,  in 


Fig.  394. — Refraction  by 
a  Biconcave  Lens. 


Fig.  395. — Formation  of  Image  by  Biconcave  Lens. 


passing  through  a  body  some  of  the  light  is  transformed  into  heat,  a 

portion  of  the  energy  of  the  short,  luminous  waves  going  to  increase  the 

vibrations  of  the  molecules  of  the  medium,  just  as  a  wave  passing  under 

a  row  of  barges  or  fishing-boats  set  them  swinging  and  pitching,  and  so 

imparts  to  them  a  certain  amount  of  energy,  which  is  ultimately  changed 

^nto  heat  by  friction  against  the  water,  and  against  each  other,  and  by 

the  straining  and  rubbing  of  the  chains  at 

their   points   of    attachment.      Some    bodies 

absorb  all  the  rays  in  the  proportion  in  which 

they  occur  in  white  light;  whether  looked  at 

or  looked  through,  they  appear  colourless  or 

white.     Other  substances  absorb  certain  rays 

by  preference,  and  the  amount  of  absorption 

is  proportional  to  the  thickness  of  the  layer. 

The  colours  of  most  natural  bodies  are  due  to  ^ 

this  selective  absorption.     Even  when  looked 

at  in  reflected   light,  they  are  seen  by  rays 

that  have  penetrated  a  certain  way  into  the 

substance  and  have  then  been  reflected;  and, 

of  course,  a  smaller  number  of  the  rays  which 

the  body  specially  absorbs  are  reflected  than 

of  the  rays  which  it  readily  transmits,  for 

more  of  the  latter  than  of  the  former  reach 

any  given  depth.   This  is  called  '  body  colour  '; 

and  such  substances  have  the  same  colour 

when   seen  by  reflected  and  by  transmitted 

light.     The  colour  of  haemoglobin  is  due  to 

the  absorption  of  the  violet  and  many  of  the 

yellow  and  green  rays,  as  is  shown  by  the 

position  of  the  absorption  bands  in  its  spectrum  (p.  51).     In  Fig.  396  the 

violet  rays  are  represented  as  being  totally  absorbed   before  passing 

through  the  substance.     Sjome   of  the  green  rays  are  reflected,  some 

transmitted,  some  absorbed.     The  red  rays  are  supposed  to  be  mostly 

reflected  and  transmitted,  only  to  a  slight  extent  absorbed.     The  colour 

of  suc?h  a  substance,  both  when  looked  at  and  when  looked  through, 


^^^4^ 

■"\ 

/ 

!!!''!::ip:  - 

\.' 

■■/ 

',"!///'  f 

HUH 

Fig.  396.— Diagram  to  show 
Connection  of  Body  Colour 
with  Selective  Absorption. 


VISION 


973 


would  therefore  be  that  due  to  a  mixture  of  red  light  with  a  smaller 
quantity  of  green.  Then  there  is  another  class  of  substances  which  owe 
their  colour  to  selective  reflection.  Certain  rays  only  arc  reflected  from 
their  surface,  and  the  light  transmitted  through  a  thin  layer  is  com- 
plementary to  the  reflected  light — that  is,  the  reflected  and  transmitted 
rays  together  would  make  up  white  light.  These  bodies  have  what  is 
called  '  surface  colour.'  and  include  metals,  various  aniline  dyes,  and 
other  substances. 

Comparative. — Many  invertebrate  animals  possess  rudimentary  sense- 
organs,  by  means  of  which  they  may  receive  certain  luminous  impres- 
sions. It  is  true  that  the  mere  sensation  of  light  is  not  in  itself  sufficient 
for  the  exact  appreciation  of  the  form  and  situation  of  surroundingobjects. 
But  even  the  closure  of  the  eyelids  does  not  prevent  a  person  of  normal 
eyesight  from  distinguishing  differences  in  the  intensity  of  illumination. 


Cornea 


-N.   -Suspensorjf 
.s''  )  Ligament 

-Choroid 


-hScleroiic 


'/-•-■Retina 


Fig-  397- — Diagrammatic  Horizontal  Section  of  the  Left  Eye. 


And  it  is  possible  that  many  of  the  humbler  animals  may,  through  the 
pigment  spots  which  are  often  called  eyes,  or  perhaps,  as  in  the  earth- 
worm, by  means  of  end-organs  more  generally  diffused  in  the  skin, 
attain  to  some  such  dim  consciousness  of  light  and  shadow  as  will  enable 
them  to  avoid  an  obstacle  or  an  enemy,  to  seek  the  sunny  side  of  a 
bouUier  or  the  obscurity  of  an  overhanging  ledge  of  rock.  But  the 
indispensable  conilition  of  distinct  vision  is  that  an  image  of  each  part 
of  an  object  should  be  formed  upon  a  separate  portion  of  the  receiving 
or  sensitive  surface.  This  condition  is,  to  a  certain  exentt,  fulfilled  by 
the  comjx)und  eyes  of  some  of  the  higher  invertebrates  (insects,  e.g.). 
Here  rays  from  one  point  of  the  object  pass  through  one  of  the  funnel- 
shaped  elements  of  the  compound  eye,  and  rays  from  another  jK)int 
through  another.  Rays  striking  obliquely  on  the  facets  are  stopped 
by  the  opaque  partitions  between  them.      In  tlie  Cephalopx)ds  we  find 


974 


THE  SENSES 


Coues. 


that  this  compound  type  of  eye  has  already  been  abandoned ;  the  single 
system  of  curved  refracting  surfaces  so  characteristic  of  the  vertebrate 
eye  has  made  its  appearance ;  and  the  formation  of  a  clean-cut  image 
of  the  object  on  the  retina,  with  the  excitation  of  a  sharply-bounded  area 
of  that  membrane,  follows  as  a  geometrical  consequence  from  the  theory 
of  lenses. 

We  have  to  consider  (i)  the  mechanism  by  which  an  image  is 
formed  on  the  retina,  and  (2)  the  events  that  follow  the  formation 
of  such  an  image  and  their  relations  to  the  stimulus  that  calls  them 
forth. 

Structure  of  the  Eye. — The  eye  may  be  described  with  sufficient 
accuracy  as  a  spherical  shell,  transparent  in  front,  but  opaque  over 

the  posterior  five-sixths  of  its 
surface,  and  filled  up  with  a 
series  of  transparent  liquids 
and  solids.  The  shell  consists 
of  three  layers  concentrically 
arranged,  like  the  coats  of  an 
onion:  (i)  An  external  tough, 
fibrous  coat,  the  sclerotic,  the 
anterior  portion  of  which 
appears  as  the  white  of  the  eye. 
In  front  this  external  layer  is 
completed  by  the  transparent 
cornea.  (2)  A  vascular  layer, 
the  choroid,  which,  in  the  re- 
stricted sense  of  the  term,  ends 
in  front  in  a  series  of  folds  or 
plaits,  the  ciliary  processes.  The 
choroid  contains  a  greater  or 
smaller  quantity  of  the  black 
pigment  melanin.  The  ciliary 
processes  abut  on  the  outer 
boundary  of  the  iris,  which 
may  be  looked  upon  as  an 
anterior  continuation  of  the 
choroidal  or  middle  coat  of  the 
eyeball.  Between  the  corneo- 
_._...-.-.  -  sclerotic  junction  and  the  an- 

Fig.   398.— Diagram  of  Structure  of  Retina     terior  portion  of  the  choroid  is 


(after  Cajal).  H,  layer  of  nerve-fibres;  G, 
layer  of  ganglion  cells;  F,  internal  mole- 
cular layer;  E,  internal  nuclear  layer; 
C,  external  molecular  layer;  B,  external 
nuclear  layer;  external  limiting  membrane  ; 
A ,  layer  of  rods  and  cones. 


interposed  a  ring  of  unstriped 
muscular  fibres,  the  ciliary 
muscle.  (3)  The  inner  or  sen- 
sitive coat,  termed  the  retina 
(Fig.  398).  This  covers  the 
choroid  as  a  delicate  mem- 
brane, extending  to  the  ciliary  processes,  where  it  ends  in  a 
toothed  margin,  the  ora  serrata.  The  optic  nerve  forms  a  kind  of 
stalk  to  which  the  eyeball  is  attached.  Its  point  of  entrance  at 
the  optic  disc  is  a  little  nearer  the  median  line  than  the  antero-posterior 
axis,  which  nearly  passes  through  the  centre  of  a  small  depression, 
the  fovea  centralis,  situated  in  the  middle  of  the  macula  lutea,  or 
yellow  spot.  From  the  optic  disc  (somctimts  called  the  optic 
papilla)  the  optic   nerve  spreads  over   the   retina  as  a  layer  of  non- 


VISION 


975 


mcdullated  fibres,  separated  from  tlir-  interior  of  the  eyeball  only 
by  the  internal  limiting  membrane.  1  l.is  so-talkd  membrane  is  formed 
by  the  expanded  feet  of  the  fibres  of  Muller,  which  run  like  a  scaffolding 
or  framework  through  nearly  the  whole  thickness  of  the  retina,  ter- 
minating at  the  outer  limiting  membrane.  External  to  the  layer  of 
nerve-fibres  is  the  stratum  of  large  ganglion  cells,  whose  axons  they 
are;  next  to  this  the  inner  molecular  layer,  or  inner  synapse  layer, 
made  up  largely  of  the  branching  dendrites  of  these  cells.  The  fiftli 
layer  is  the  inner  granular  or  nuclear  layer,  containing  many  fusiform 
(bipolar)  '  granule  '  cells  which  send  out  axons  into  the  fourth,  and 
dendrites  into  the  sixth,  or  outer  molecular  layer,  and  are  thus  con- 
nected with  the  ganglion  cells  of  the  third  layer  on  the  one  hand,  and 
with  the  terminations  of  the  rod  and  cone  fibres  of  the  seventh  or  outer 
nuclear  layer  on  the  other.  The  arborizations  of  tlie  axons  of  these 
bipolar  cells  are  situate  at  different 
levels  in  the  internal  molecular 
layer.  The  bipolar  cells  connected 
with  the  rod  fibres  send  their  axons 
right  through  the  internal,  mole- 
cular layer  to  arborize  around  the 
bodies  of  the  ganglion  cells,  whereas 
the  axons  of  the  bipolar  cells  con- 
nected with  the  cone  fibres  ram  if  > 
about  the  middle  of  the  layer 
(Fig.  398).  The  seventh  stratum 
receives  its  name  from  the  large 
number  of  nuclei  which  it  contains. 
These  belong  to  structures  con- 
tiniuius  with  the  rods  and  cone  s 
of  the  ninth  layer,  which  is  divide  d 
from  the  seventh  by  the  exterral 
limiting  membrane.  Each  rod  is 
prolonged  into  the  external  nuclear 
layer  as  a  fine  fibre,  which  has  on 
its  course  a  swelling  containing  a 
nucleus,  and  terminates  (in  mam- 
mals) in  a  fine  knob  in  the  extern;  1 
molecular  layer  among  the  den- 
drites of  the  bipolar  cells.  Each 
cone  of  the  rod  and  cone  layer  is 

directly  prolonged  into  a  nucleated  enlargement  in  the  external  nuclear 
layer.  From  this  enlargement  a  fibre  (cone  fibre),  of  considerably  greater 
calibre  (in  mammals)  than  the  rod  fibre,  passes  into  the  external  mole- 
cular layer,  where  it  forms  an  arborization,  which  comes  into  relation 
with  the  arborization  of  the  dendrites  of  a  bipolar  cells.  At  the  fovea 
centralis  the  rods  are  entirely  absent,  and  the  other  layers  of  the  retina 
greatly  thinned;  over  the  optic  disc  neither  rods  nor  cones  are  present. 
The  disc  is  pierced  by  the  retinal  bloodvessels  (Fig.  y^)). 

External  to  the  rods  and  cones  is  a  sheet  of  pigmented  epithelial  cells 
of  hexagonal  shape,  belonging  to  the  choroid,  but  remaining  attached 
to  the  retina  when  the  latter  isj^eparated,  and  therefore  often  reckoned 
as  its  most  external  layer. 

A  little  beliind  the  cornea  and  anterior  to  the  retina  is  the  letis.  en- 
closed in  a  capsule,  anel  attaelud  to  the  choroid  by  the  susponsor\' 
ligament,  or  zonule  of  Zinn.  The  ins  hangs  down  in  front  of  the  lens 
like  a  diaphragm,  with  a  central  hole,  the  pupil.     Incorporated  in  the 


Fig.  399. — Retinal  Bloodvessels  (Henle). 
The  arteria  centralis  is  seen  issuing 
from  the  optic  dies  and  branching  over 
the  retina.  The  shaded  area  in  the 
middle  of  the  figure  represeats  the 
yellow  spot  with  the  fovea  centralis  in 
its  centre. 


976  THE  SENSES 

stroma  or  framework  of  the  iris  are  two  arrangements  of  smooth  mus- 
cular fibres,  which  confer  on  it  the  power  of  adjusting  the  size  of  the 
pupil.  One  of  these — the  sphincter  pupillae — consists  of  a  well-defined 
band  of  concentric  fibres  surrounding  the  margin  of  the  pupil.  The 
other — the  dilator  pupillae — is  less  sharply  differentiated.  It  is  repre- 
sented by  radial  bundles  of  elongated,  spindle-shaped  cells  running  in 
from  the  ciliary  border  of  the  iris  towards  the  pupil.  Between  the  iris 
and  the  posterior  surface  of  the  cornea  is  the  anterior  chamber  of  the 
eye.  filled  with  the  aqueous  humour.  Between  the  iris  and  the  anterior 
surface  of  the  lens  lies  the  posterior  chamber,  which  is  rather  a  potenial 
than  an  actual  cavity.  The  space  between  the  lens  and  the  retina  is 
accurately  occupied  by  an  almost  structureless  semi-fluid  mass,  the 
vitreous  humour,  enclosed  by  the  delicate  hyaloid  membrane,  which  in 
front  is  reflected  over  the  folds  of  the  ciliary  processes,  and  blends  with 
the  suspensory  ligament  of  the  lens.  The  attachment  of  the  suspensory 
ligament  is  rendered  firmer  by  the  connection  of  this  part  of  the  hyaloid 
membrane  to  a  circular  fibrous  portion  of  the  vitreous-.  Around  the 
edge  of  the  lens  is  left  a  space,  the  canal  of  Petit. 

Chemistry  of  the  Refractive  Media. — The  aqueous  humour  is  a  per- 
fectly colourless,  watery  liquid,  of  slightly  alkaline  reaction  to  litmus. 
The  specific  gravity  is  about  1008,  and  the  total  solids  about  i  per 
cent.  Of  the  solids  the  inorganic  salts  (mainly  sodium  chloride)  con- 
stitute much  the  largest  portion.  A  very  small  amount  of  protein 
(o'Oi  to  0-04  per  cent.)  is  present,  also  a  little  dextrose  (0-05  per  cent.), 
and  minute  traces  of  urea  and  other  substances.  The  liquid  of  the 
vitreous  humour  has  a  very  similar  composition,  except  that  it  contains 
a  mucin-like  body,  hyalomucoid,  to  the  amount  of  o-o6  to  o-i  per  cent. 
A  similar  mucin-like  substance  is  present  in  the  cornea.  The  freezing- 
point  of  both  liquids  is  a  little  lower  than  that  of  blood-serum,  A  being 
ibout  o-6°. 

The  lens  is  far  richer  in  solids  than  the  aqueous  and  vitreous  humours 
with  which  it  is  in  contact  (30  to  35  per  cent  of  solids,  60  to  65  per  cent, 
of  water).  The  salts,  with  small  quantities  of  lecithin  and  cholesterin, 
make  up  about  i  per  cent. ;  the  balance  of  the  solids  consists  of  proteins. 
The  physical  alterations,  with  production  of  turbidity,  which  occur  in 
the  lens,  and  presumably  in  its  proteins,  when  water  enters  or  leaves 
it  in  too  great  amount  through  imbibition  or  osmosis,  are  of  importance 
in  connection  with  the  etiology  of  cataract.  The  anatomical  and 
physiological  integrity  of  its  capsule  is  a  prime  factor  in  the  maintenance 
of  that  high  degree  of  transparency  which  is  necessary  for  the  function 
of  the  lens.  Cataract  can  be  experimentally  induced  by  injuring  the 
capsule.  In  like  manner  the  cornea  is  protected  against  injurious 
changes  in  its  water-content  (normally  about  80  per  cent.)  and  conse- 
quent turbidity  by  the  epithelium,*  which  separates  it  from  the  tears, 
and  the  endothelium,  which  separates  it  from  tl;e  aqueous  humour. 

Secretion  of  the  Intra-ocular  Liquids. — The  aqueous  humour  is 
secreted  by  the  uveal  epithelium  covering  the  ciliary  processes,  and 
to  some  extent  by  that  covering  the  iris.  As  it  is  continually  secreted, 
so  it  is  continually  absorbed,  the  absorbed  constituents  finding  their 
way  eventually  into  the  vein  or  venous  sinus  called  the  canal  of  Schlemm 
and  the  bloodvessels  of  the  iris  and  ciliary  processes.  The  source  of 
the  liquid  of  the  vitreous  body  is  also  tke  uvea.  While  the  intra-ocular 
liquids  differ  from  ordinary  lymph,  there  is  no  reason  to  doubt  that  they 
are  secretions  which  contribute  to  the  nutrition  of  those  transparent 
structures  of  the  eye  which  are  not,  and,  on  account  of  their  function, 
cannot  be  supplied  with  bloodvessels.     Their  most  obvious  use  is  to 


VISION  977 

maintain  the  proper  intra-ocular  pressure  on  which  the  geometrical 
figure  of  the  eyeball,  and  therefore  its  effaicncy  as  an  optical  instrument, 
depend.  The  balance  l)etween  secretion  and  absorption  is  accurately 
adjusted  in  health,  but  in  disease  it  may  be  upset,  as  in  glauc/)ma,  where 
the  intra-ocular  tension  is  so  much  increased  as  to  interfere  with  the 
circulation,  and  injuriously  affect  the  nutrition  and  function  of  the  retina. 
Experimentally,  occlusion  of  all  the  arteries  supplying  the  head  causes 
a  rapid  fall  of  tension,  and  tlie  cornea  becomes  wrinkled  and  slack  to 
the  touch.  On  restoring  the  circulation  after  not  too  long  an  interval, 
the  tension  gradually  returns  to  normal,  and  then  becomes  markedly 
hypernormal,  even  when  the  general  arterial  pressure  is  still  low.  This 
is  probably  due  to  the  crippling  of  the  elements  which  secrete  and 
absorb  tlie  intra-ocular  fluids,  or  of  the  capillary-  walls,  so  that  a  proper 
adjustment  can  no  longer  be  attained,  as  happens  in  a  tissue  rendered 
oedematous  by  temporary  anaemia.  Where  asphyxia  of  the  eyeball  is 
avoided  or  is  brieithe  intra-ocular  pressure  varies  directly  as  the  blood- ' 
pressure  intheocularvesselswitliin  a  wide  range  (Henderson  and  Starling). 

Refraction  in  the  Eye — Formation  of  the  Retinal  Image. — The 

amount  of  refraction  which  a  ray  of  hght  undergoes  at  a  ctirved 
surface  depends  upon  two  factors — the  radius  of  curvature  of  the 
surface,  and  the  difference  between  the  refractive  indices  of  the 
media  from  which  the  ray  comes  and  into  which  it  passes.  The 
smaller  the  radius  of  curvature,  and  the  greater  the  difference  of 
refractive  index,  the  more  is  the  ray  bent  from  its  original  direction. 
A  ray  of  light  passing  into  the  eye  meets  first  the  approximately 
spherical  anterior  surface  of  the  cornea,  covered  with  a  thin  layer 
of  tears.  Since  the  refractive  index  of  the  tears  is  much  greater 
than  that  of  air,  the  ray  is  strongly  refrrcted  here.  The  anterior 
and  posterior  surfaces  of  the  cornea  being  practically  parallel,  and 
the  refractive  indices  of  the  tears  and  aqueous  humour  being  nearly 
equal,  but  little  refraction  takes  place  in  the  cornea  itself.  At  the 
anterior  and  posterior  surfaces  of  the  lens  the  ray  is  again  refracted, 
since  the  refractive  index  of  the  aqueous  and  vitreous  humours  is 
less  than  that  of  the  lens.  The  following  tables  show  the  radii  of 
curvature  of  the  refracting  surfaces  and  the  refractive  indices  of 
the  dioptric  media,  as  well  as  some  other  data  which  |are  of  use  in 
studying  the  problems  of  refraction  in  the  eye : 


rCornea     -         -         -         - 
Radius  of  curvature  oi<  .\nterior  surface  of  lens    - 
i  Posterior  surface  of  lens  - 
'.\nterior   surface   of    cornea   and     an- 
terior surfiice  of  lens  ... 
Distance     .Anterior  surface    of   cornea   and    pos- 
bctween          terior  surface  of  lens          -         .         . 
Anterior  and  posterior  surface  of  lens  - 
.Posterior  surface  of  lens  and  retina 
Antero-posterior  diameter  of  eye  along  the  axis    - 


In 

accommodation  for 

Far  \ 

i-i'in. 

Nc.ir  Vixioii. 

7-8 

mm. 

7'8  mm. 

lo-o 

, , 

6-0     .. 

60 

'• 

5-5     .. 

3-6 

.. 

3-^     .. 

7.6 

J  J 

7-^     : 

4-0 
146 

•' 

4-4     .. 
146     .. 

22-2 

•• 

2  2-2       ., 
02 

978 


THE  SENSES 


Refractive  Indices — 

Air  ...  - 

Cornea  -         -         -         - 
Aqueous  humour    - 
Vitreous  humour    - 
Lens  (total  refractive  index) 
Water    -         -         -         - 


I -000 

1-377 

1-3365 

1-3365 

1-437 

1-335 


It  will  be  seen  that  the  refractive  indices  of  the  aqueous  and  vitreous 
humours  are  nearly  the  same  as  that  of  water.  That  of  the  lens 
differs  for  its  various  layers,  the  central  core  having  a  higher  re- 
fractive index  (1-411)  than  the  more  superficial  portions  (1-388). 
Although  such  calculations  are  open  to  error,  it  has  been  computed 
that  the  lens  acts  as  a  homogeneous  lens  of 
the  same  curvatures,  and  with  a  refractive 
index  of  1-437  would  do.  This  is  called  the 
total  refractive  index  of  the  lens..  The 
apparent  paradox  that  it  is  greater  than  the 
refractive  index  even  of  the  core  is  explained 
by  the  consideration  that  the  core  taken  by 
itself  has  a  greater  curvature  than  the  entire 
lens,  and  therefore  causes  a  greater  amount  of 
refraction  in  proportion  to  its  refractive  index. 
The  optical  problems  connected  with  the 
formation  of  the  retinal  image  are  complicated 
b}^  the  existence  in  the  eye  of  several  media, 
with  different  refractive  indices,  bounded  by 
surfaces  of  different  and,  in  certain  cases,  of 
variable  curvature.  For  many  purposes,  how- 
ever, the  matter  can  be  greatly  simphfied,  and 
a  close  enough  approximation  yet  arrived  at, 
by  considering  a  single  homogeneous  medium, 
of  definite  refractive  index,  and  bounded  in 
front  by  a  spherical  surface  of  definite  curva- 
ture, to  replace  the  transparent  solids  and 
liquids  of  the  eye.  The  principal  focus  being  supposed  to  lie 
on  the  retina,  the  position  of  the  nodal  point — i.e.,  the  point 
through  which  rays  pass  without  refraction — of  such  a  '  reduced  ' 
or  '  schematic  '  or  '  simplified  '  eye,  and  other  constants,  are  shown 
in  the  following  table.  The  single  refracting  surface  would  be 
situated  behind  the  cornea  and  in  front  of  the  lens,  at  a  rather 
smaller  distance  from  the  anterior  surface  of  the  latter  than  from 
the  anterior  surface  of  the  former.  The  nodal  point  would  be  less 
than  half  a  millimetre  in  front  of  the  posterior  surface  of  the  lens 
(Fig.  400).  The  refractive  index  of  the  single  transparent  medium 
would  be  a  little  srreater  than  that  of  water. 


Fig.  400. — The  Reduced 
Eye.  S,  the  single 
spherical  refracting 
surface,  22  mm.  be- 
hind  the  anterior  sur- 
face  of  the  cornea;  N, 
the  nodal  point,  5  mm. 
behind  S  ;  F,  the 
principal  focus  (on  the 
retina),  20  mm.  behind 
S.  The  cornea  and 
lens  are  put  in  in 
dotted  lines  in  the 
position  which  they 
occupy  in  the  normal 
eye. 


VISION  979 

Reduced  Eye — 
Radius  of  curv.ilurc  of  the  single  refracting  surface  -       5'i      mm. 

Index  of  refraction  of  the  single  refracting  medium  -         -       i'35*  .. 
Antero-posterior   diameter   of    reduced    eye    (distance    oi 

principal  focus  from  the  single  refracting  surface)  -     ^o-o 

Distance    of    the    single    refracting    surface    behind    the 

anterior  surface  of  the  cornea        .         -         .         .         -       2-2       ,, 
Distance  of    the   nodal    point   of    the   reduced    eye    from 

|its  anterior  surf;'.(e  -         -         -         -         -         -         -5-0,, 

Distance    of    the    nodal    \K>int    from   the   principal   focus 

(retina)  ----------     15-0 

Knowing  the  position  of  the  centre  of  curvature  of  the  single 
ideal  refracting  surface — i.e.,  the  nodal  point  of  the  reduced  eye 
— all  that  is  necessary  in  order  to  determine  the  position  of  the 
image  of  an  object  on  the  retina  is  to  draw  straight  lines  from  its 
circumference  through  the  nodal  point.  Each  of  these  lines  cuts 
the  refracting  surface  at  right  angles,  and  therefore  passes  through 
without  any  devi- 
ation. The  retinal 
image  is  accord- 
ingly inverted  and 
its  size  is  propor- 
tional to  the  solid 
angle  contained 
between  the  lines 
drawn  from  the 
boundary  of  the  Fig.  401.— Figure  to  show  how  the  Visual  Angle  and  Size 
object  to  the  nodal  o^  Retinal  image  varies  with  the  Distance  of  an  Object 

•    ,  ,,  1  of  Given  Size.    For  the  distant  position  of  AB  the  visual 

pomt,  or  tne  equal  ^^^^  -^  ^  ^^^  ^^^  ^^^j.  position  (dotted  lines)  /3. 

angle  contained  by 

the  prolongations  of  the  same  lines  towards  the  retina.  This  angle 
is  called  the  visual  angle,  and  evidently  varies  directly  as  the  size 
of  the  object,  and  inversely  as  its  distance.  Thus  the  visual  angle 
under  which  the  moon  is  seen  is  much  larger  than  that  under  which 
we  view  any  of  the  fixed  stars,  because  the  comparative  nearness  of 
the  earth's  satellite  more  than  makes  up  for  its  relatively  small  size. 

The  dimensions  of  the  retinal  image  of  an  object  arc  easily  calculated 

when  the  size  of  the  object  and  its  distance  are  known.     For  let  AB 

in  Fig.  401  represent  one  diameter  of  an  object,  A'B'  the  image  of  this 

diameter,  and  let  AB',  BA'.  be  straight  lines  passing  through  the  nodal 

point.     Then  AB  and  A'B'  may  be  considered  as  parallel  lines,  and 

the  triangles  of  whii  h  they  form  the  bases,  and  the  nodal  point  the 

common  apex,  as  similar  triangles.     Accordingly,  if  D  is  the  distance 

of  the   nodal   point  from   A.   and   d  its  distance  from    B',    we   have 

\B     \'B' 

'--  =  '— — .     Now,  d  may  approximately  be  taken  as  15  mm.     Suppose. 

then,  that  the  size  of  the  moon's  image  on  the  retina  is  required.  Here 
D=  238,000  miles,  and  AB  (the  diameter  of  the  moon)=2.itx)  miles. 

•  Or  a  little  more  than  that  of  the  aqueous  humour. 


98o  THE  SENSES 

Ti,   ^  ^     2,160       A'B'  ,       ,     1        A'B'    ,  1  ■  ,     .  ,T-./  ,., 

Thus  we  get  — r, = ,  or  (say)   —  = ,  from  which  A'B'  (the 

°      238,000       15  ^    •"  no       15  ^ 

diameter  of  the  retinal  image)  =  — — ,  or  about  I  mm. 

°  '     no  ^ 

A  ship's  mast  120  feet  high,  seen  at  a  distance  of  25  miles,  will  throw 

on   the   retina    an    image    whose    height   is    — r^r^xi's    mm.,    i.e., 

°  °  25  miles       ^ 

120  feet  I  ,   , 

— 5 7 — tX  15  mm.,  or  x  15  mm.,  equal  to  o-oi^  mm.,  or 

5,280x25  feet       -^  1,100       -»  -1  J  ■ 

13  /x  in  size.     This  is  not  much  larger  than  a  red  blood-corpuscle,  and 

only  four  times  the  diameter  of  a  cone  in  the  fovea  centraHs,  where  the 

cones  are  most  slender.     In  this  calculation  the  effect  of  aberration 

(p.  987)  in  enlarging  the  image  has  been  neglected.     This  effect  is,  of 

course,  proportionately  greater  for  small  and  distant  than  for  large  and 

near  objects;  and  it  is  doubtful  whether  the  smallest  possible  image 

can  be  confined  to  an  area  of  the  retina  of  the  size  of  a  single  cone. 

Accommodation. — A  lens  adjusted  to  focus  upon  a  screen  the 
rays  coming  from  a  luminous  point  at  a  given  distance  will  not  be 
in  the  proper  position  for  focussing  rays  from  a  point  which  is 
nearer  or  more  remote.  Now,  it  is  evident  that  a  normal  eye 
possesses  a  great  range  of  vision.  The  image  of  a  mountain  at  a 
distance  of  30  miles,  and  of  a  printed  page  at  a  distance  of  30  cm., 
can  be  focussed  with  equal  sharpness  upon  the  retina.  In  an 
opera-glass  or  a  telescope  accommodation  is  brought  about  by 
altering  the  relative  position  of  the  lenses;  in  a  photographic  camera 
and  in  the  eyes  of  fishes  and  cephalopods,  by  altering  the  distance 
between  lens  and  sensitive  surface ;  in  the  eye  of  man,  by  altering 
the  curvature,  and  therefore  the  refractive  power  of  the  lens.  That 
the  cornea  is  not  alone  concerned  in  accommodation,  as  was  at  one 
time  widely  held,  is  shown  by  the  fact  that  under  water  the  power 
of  accommodation  is  not  wholly  lost.  Now,  the  refractive  index 
of  the  cornea  being  practically  the  same  as  that  of  water,  no  changes 
of  curvature  in  it  could  affect  refraction  under  these  circumstances. 
That  the  sole  effective  change  is  in  the  lens  can  be  most  easily 
and  decisively  shown  by  studying  the  behaviour  of  the  mirror 
images  of  a  luminous  object  reflected  from  the  bounding  surfaces 
of  the  various  refractive  media  when  the  degree  of  accommodation 
of  the  eye  is  altered.  Three  images  are  clearly  recognized:  the 
brightest  an  erect  virtual  image,  from  the  anterior  (convex)  surface 
of  the  cornea;  an  erect  virtual  image,  larger,  but  less  bright,  from 
the  anterior  (convex)  surface  of  the  lens;  and  a  small  inverted  real 
image  from  the  (concave)  posterior  boundary  of  the  lens  (Purldnje- 
Sanson  images).  The  second  image  is  intermediate  in  position 
between  the  other  twoi  It  is  possible  with  special  care  to  make 
out  a  fourth  image;  but  since  it  is  reflected  from  the  posterior 
sifrface  of  the  cornea,  at  which  only  a  slight  change  in  the  refractive 
index  occurs,  it  is  less  brilliant  than  the  first  three.  When  the  eye 
is  accommodated  for  near  vision,  as  in  focussing  the  ivory  point  of 


VISION 


98  r 


the  phakoscope  (Practical  Exercises),  the  corneal  image  is  unchanged 
in  si7X',  brightness,  and  position.  The  mifldlc  image  diminishes 
in  size,  comes  forward,  and  moves  nearer  to  the  corneal  image. 
This  shows  that  the  curvature  of  the  anterior  surface  of  the  lens 
has  been  increased — that  is  to  say,  its  radius  of  curvature  diminished 
— for  the  size  of  the  image  of  an  object  reflected  from,  a  convex 
mirror  varies  directly  as  the  radius  of  curvature.  A  slight  change 
takes  place  in  the  image  from  the  posterior  surface  of  the  lens, 
indicating  a  small  increase  of  its  curvature  too.  |By  means  of  a 
method  founded  on  the  observation  of  the  changes  in  these  images, 
and  a  special  instrument  called  an  (ophthalmometer  which  allows 
of  their  measurement,  Helmholtz 
has  calculated  that  during  maxi- 
mum accommodation,  the  radius 
of  cuivature  of  the  anterior  surface 
of  the  lens  is  only  6  mm.,  as  com- 
pared with  10  mm.  when  the  eye 
is  directed  to  a  distant  object  and 
there  is  no  accommodation.  When 
the  lens  has  been  removed  for 
cataract,  fairly  distinct  vision  may 
still  be  obtained  by  compensating 
for  its  loss  by  convex  spectacles 
of  suitable  refractive  power  (10 
diopters*  for  distant  vision,  and 
15  diopters  for  the  distance  at 
which  a  book  is  usually  held),  but 
no  power  of  accommodation  re- 
mains. The  person  does  indeed 
contract  the  pupil  in  regarding  a 
near  object,  just  as  happens  in  the 
intact  eye;  the  most  divergent 
rays  are  thus  cut  off  and  the  image 
made  somewhat  sharper,  and  there 
may  appear  to  be  some  faculty  of 
accommodation  It- ft.  But  the  loss 
of  the  whole  iris  by  operation  does 
not  affect  accommodation  in  the  least;  the  iris,  therefore,  takes 
no  part  in  it.  That  no  change  in  the  antero-posterior  diameter 
of  the  eyeball,  caused  by  its  deformation  by  the  contraction  of  the 
extrinsic  muscles,  can  have  any  share  in  accommodation,  as  has 

•  A  diopter  (i  D.)  is  the  unit  of  refractive  power  Rencrally  adopted  in 
measuring  the  strength  of  lenses,  and  corresponds  to  a  lens  of  i  metre  focal 
length.  A  lens  of  2  diopters  (2  D.)  has  a  focal  length  of  h  metre,  a  lens  of 
4  diopters  (4  D.)  a  focal  length  of  J  metre,  and  so  on.  I'he  diverging  power 
of  concave  lenses  is  similarly  expressed  in  tliopters  with  the  negative  sign 
prefixed.  Thus,  a  concave  lens  of  i  metre  focal  hnL'th  h. is  .1  strenrtii  oi  -  i  D., 
and  will  just  neutralize  a  convex  lens  of  t  I>. 


Fig.  402. — Purkinje  -  Sanson  Images. 
A,  in  the  absence  of  accu;iniioda- 
tion;  B.  during  accommodation  for 
a  near  object.  The  upper  pair  of 
circles  enclose  the  images  as  seen 
when  the  light  falls  on  the  eye 
through  a  double  slit  on  a  i>air  of 
prisms;  the  lower  pair  show  the 
images  seen  when  the  slit  is  single 
and  triangular  in  shape. 


^82  THE  SENSES 

been  suggested,  is  clearly  proved  by  the  fact  that  atropine,  which 
does  not  affect  the  action  of  these  muscles,  paralyzes  the  mechanism 
of  accommodation.  To  the  consideration  of  that  mechanism  we 
now  turn. 

The  Mechanism  of  Accommodation. — While  everybody  is  agreed 
that  the  main  factor  in  accommodation  is  the  alteration  in  the 
curvature  of  the  lens,  there  is  by  no  means  the  same  unanimity 
as  to  the  manner  in  which  this  is  brought  about.  Helmholtz's 
explanation,  which  has  long  been  the  most  popular,  is  as  follows: 
In  the  unaccommodated  eye  the  suspensory  ligament  and  the 
capsule  of  the  lens  are  tense  and  taut,  the  anterior  surface  of  the 
lens  is  flattened  by  their  pressure,  and  parallel  rays  (or,  what  is  the 
same  thing,  rays  from  a  distant  object)  are  focussed  on  the  retina 
without  any  sense  of  effort.  In  accommodation  for  a  near  object, 
the  meridional  or  antero-posterior  fibres  of  the  ciliary  muscle  by 
their  contraction  pull  forward  the  choroid  and  relax  the  suspensory 
ligament.  The  elasticity  of  the  lens  at  once  causes  it  to  bulge 
forwards  till  it  is  again  checked  by  the  tension  of  the  capsule. 

The  explanation  of  Helmholtz,  although  widely  adopted  in  the  text- 
books, has  not  escaped  question  in  the  archives.  Tscherning  has  put 
forward  the  view  that  when  the  ciliary  muscle  contracts,  the  suspensory 
ligament  is  pulled  backwards  and  outwards.  Its  tension  is  thus  in- 
creased, and  the  soft  external  layers  of  the  ,lens  are  in  consequence 
moulded  upon  the  harder  nucleus,  so  as  to  increase  the  curvature 
especially  around  the  anterior  pole.  And  Schoen,  reviving  a  similar 
theory  originated  fifty  years  ago  by  Mannhardt,  believes  that  the 
ciliary  muscle,  in  contracting,  exerts  pressure  on  the  anterior  portion 
of  the  lens,  and  so  increases  its  curvature.  He  likens  the  process  to  the 
bulging  of  an  indiarubber  ball  when  it  is  held  in  both  hands  and  com- 
pressed by  the  fingers  a  little  behind  one  of  the  poles.  It  will  be  ob- 
served that  in  both  of  these  theories  the  suspensory  ligament  is  supposed 
to  be  stretched  during  accommodation,  not  relaxed  as  Helmholtz  sup- 
posed. While  they  have  certain  advantages  over  the  theory  of  Helm- 
holtz, particularly  in  taking  account  of  the  presence  of  radial  and  circular 
as  well  as  meridional  fibres  in  the  ciliary  muscle,  they  do  not  agree  so 
well  with  such  experimental  tests  as  have  been  applied,  and  therefore 
Helmholtz's  explanation  must  still  be  regarded  as  the  best. 

It  is  supported  by  the  observation  of  Hess  that  when  the  ciliary 
muscle  has  been  very  strongly  contracted  by  eserine  the  lens  can  be 
observed  to  move  about  with  each  slight  movement  of  the  eye.  The 
suspensory  ligament  must  therefore  be  slackened  by  the  contraction  of 
the  ciliary  muscle.  When  atropine  is  applied  the  movability  of  the 
lens  soon  disappears,  owing  to  paralysis  of  the  ciliary  muscle.  These 
facts  were  first  established  in  patients  after  iridectomy,  but  have  also 
been  demonstrated  in  the  normal  eye.  Even  under  the  influence  of 
gravity  alone,  without  any  movements  of  the  eye,  the  lens  sinks  about 
^  to  ^  mm.  in  strong  accommodation.  An  additional  proof  that  the 
suspensory  ligament  is  perfectly  slack  during  accommodation  is  derived 
from  the  result  of  simultaneous  measurements  in  animals  of  the  pressure 
in  the  anterior  chamber  and  in  the  vitreous.  Even  in  strong  accommo- 
dation no  alteration  occurs,  although  even  slight  contact  with  the  outer 
surface  of  the  eyeball  or  contraction  of  the  external  eye  muscles  causes 


VISION  9«3 

a  distinct  effect,  in  two  cavities  separated  by  a  slack  membrane  no 
differences  of  pressure  would  be  expected. 

Anderson  Stuart  lays  stress  upon  the  function  of  those  fibres  of  the 
suspensory  ligament  which  are  attached  to  the  vitreous  body,  and  are 
put  under  tension  by  the  (  ontraction  uf  the  ciliary  muscle,  in  anchoring 
the  lens  during  strong  accommodation.  He  believes  that  the  liquid 
contents  of  the  iiyaioid  canal  mc^ve  from  its  ;  nterior  to  its  posterior  end 
in  accommodation,  and  in  the  opposite  direi  lion  when  accommodation 
is  relaxed,  and  that  this  movement  tends  to  prevent  strains  in  the 
vitreous. 

In  ccphalopods  and  fishes,  which  are  normally  short-sighted,  accom- 
modation for  objects  at  a  distance  is  effected  by  a  movement  of  the  lens 
towards  the  retina.  In  the  fish's  eye  this  is  accomplished  by  the  con- 
traction of  a  special  musi:le,  the  retractor  lentis.  In  amphibia  and  most 
snakes  the  lens  is  moved  towards  the  cornea  and  away  from  the  retina 
by  changes  of  intra-ocuiar  pressure  (Beer). 

Innervation  of  the  Ciliary  Muscle  and  the  Muscles  of  the  Iris. —  1  he 
ciliary  musi  le  and  tlie  spliinLtir  pui)illa-  are  su])pli((l  by  autonomic 
fibres  (p.  964),  reaching  them  througii  the  short  ciliary  nerves  arising 
from  the  ciliary  ganglion  (Fig.  403).  The  preganglionic  fibres  take 
origin  from  cells  in  the  anterior  part  of  the  oculo-motor  nucleus  in  the 
mid-brain.  Passing  to  the  orbit  in  the  third  nerve,  they  reach  the 
ciliary  ganglion,  and  end  there  by  forming  synapses  with  some  of  its 
cells.  The  axons  of  these  cells  continue  the  path  as  post-ganglionic 
fibres  in  the  short  ciliarj'  nerves.  The  dilator  pupilla?  is  supplied  by  the 
long  ciliary  nerves  coming  from  the  ophthalmic  branch  of  the  fifth 
nerve. 

The  preganglionic  dilator  fibres  pass  out  by  the  anterior  roots  of  the 
first  three  thoracic  nerves  (dog,  cat,  rabbit),  accompanied  by  vaso- 
constrictor fibres  for  the  iris.  Reaching  the  sympathetic  chain  tlirough 
the  corresponding  rami  communicantes.  they  traverse  the  first  thoracic 
ganglion,  the  annulus  of  Vieussens,  the  inferior  cervical  ganglion,  and 
the  cervical  sympathetic.  They  end  by  arborizing  around  some  of  the 
cells  of  the  superior  cervical  ganglion,  whose  axons  eventually  arrive  at 
the  (iasserian  ganglion,  and  running  along  the  ophthalmic  division  of 
the  trigeminal  to  the  eye,  reach  the  iris  by  its  long  ciliary  branches. 

The  exact  origin  of  the  dilator  path  in  the  brain  has  not  been  defi- 
nitely settled.  Some  place  it  in  the  mid-brain,  others  in  the  bulb. 
There  must  be  at  least  one  neuron  on  the  path  central  to  the  spinal 
neuron  whose  axon  emerges  from  the  cord  as  a  preganglionic  fibre. 
The  lower  cervical  and  upper  thoracic  portion  of  the  spinal  cord  lias 
received  the  name  of  the  cilio-spinal  region  from  its  relation  to  the 
pupillo-dilator  fibres.  It  must  not  be  looked  up<ni  as  a  centre  in  any 
proper  sense  of  the  term,  but  rather  as  the  pathway  by  which  thcbc 
fibres  pass  down  from  the  bulb,  and  where  they  may  accordingly  be 
tapped  by  stimulation. 

Stimulation  of  certain  areas  on  the  cortex  of  the  frontal  lobe  of  the 
cerel)rum  (p.  962)  causes  slight  dilatation  of  the  pupil  even  after  the 
sympathetic  has  been  divided.  This  is  due  to  inhibition  of  the  pupiilo- 
constrictor  fibres  in  the  third  nerve. 

Changes  in  the  Pupil  duriag  Accommodation. — It  has  been  already  , 
mentioned  that  along  with  the  alteration  in  the  curvature  of  the 
lens  a  change  in  the  diameter  of  the  pupil  takes  place  in  accommo- 
dation.    When  a  distant  object   is  looked  at.  the  pupil  lx>conies 
larger ;  when  a  near  object  is  looked  at,  it  becomes  smaller.  Narrow- 


984 


THE  SENSES 


ing  of  the  pupil  is  thus  associated  with  contraction  of  the  ciliary 
muscle,  and  widening  of  the  pupil  with  its  relaxation. 

This  ph^^siological  correlation  has  its  anatomical  counterpart ;  for  the 
third  nerve  supplies  both  the  iris  and  the  ciliary  muscle.  Stimulation 
of  the  nerve  within  the  cranium  causes  contraction  of  the  pupil,  while 
stimulation  of  certain  portions  of  its  nucleus  in  the  floor  of  the  third 
ventricle  and  the  Sylvian  aqueduct  or  of  the  short  ciliary  ner\'es 
(Fig.  403),  which  receive  branches  from  the  third  nerve,  or  of  the 
ganglion  itself,  is  followed  by  that  change  in  the  anterior  surface  of  the 
lens  which  constitutes  accommodation  (Hensen  and  Voelckers).  This 
can  be  observed  either  through  a  window  in  the  sclerotic  in  a  dog  or  by 
following  the  movements  of  a  needle  thrust  into  the  eyeball.  Bv 
carefully  localized  stimulation  near  the  junction  of  the  aqueduct  with 


m 


2  ^^^== 


Fg  403. — Scheme  of  Innervation  of  Ciliary 
and  Iris  Muscles  (after  Schultz).  i,  ciliary 
gaugUon;  2,  oculo-motor  nucleus;  3,  spinal  cell, 
from  which  comes  off  the  preganglionic  fibre  on 
the  pupillo-dilator  path,  which  forms  a  synapse 
with  4,  a  cell  in  the  superior  cervical  ganglion. 
The  axon  of  4  is  shown  passing  (as  an  interrupted 
line)  through  the  Gasserian  ganglion  into  the 
ophthalmic  division  (Oph.)  of  the  fifth  nerve,  V, 
and  thence  in  a  long  ciliary  nerve,  5,  to  the  dilator  of  the  iris,  8.  From  i  axons 
are  shown  passing  by  short  ciliary  nerves  to  the  ciliary  muscle,  6,  and  the  constrictor 
pupillse,  7;  9.  cell  of  origin  (in  mid-brain?)  of  fibre  which  constitutes  the  central 
neuron  of  the  pupillo-dilator  path;  10,  optic  nerve;  III,  third  nerve;  V,  fifth  nerve 
with  Gasserian  ganglion. 

the  third  ventricle,  it  is  possible  to  bring  about  the  forward  bulging  of 
the  lens  without  any  change  in  the  iris :  but  the  normal  and  voluntary 
act  of  accommodation  cannot  be  disjoined  from  the  corresponding 
alterations  in  the  size  of  the  pupil.  Inward  rotation  of  the  eyes  accom- 
panies contraction  of  the  pupil  in  accommodation,  and  the  question 
may  be  raised  whether  the  pupillary  change  is  associated  with  the  action 
of  the  extrinsic  muscles  of  the  eyeball  which  cause  convergence  or  with 
the  action  of  the  intrinsic  muscles  which  determine  the  changes  in  the 
curvature  of  the  lens.  It  is  usually  considered  to  be  associated  with 
both.  In  any  case,  aciiual  convergence  is  not  necessary  for  the  reaction, 
since  it  may  still  be  obtained  on  accommodation  when  convergence  is 
impossible  on  account  of  paralysis  of  the  internal  recti. 


VISION  985 

Changes  in  the  Pupil  produced  by  Light. — It  is  not  only  by 
accommodation  that  the  size  of  the  pupil  may  be  affected.  In 
the  dark  it  dilates,  at  first  rapidly,  then  gradually,  and  it  main- 
tains the  widtli  it  has  reached  for  several  hours.  This  has  been 
shown  by  taking  photograplis  of  the  eye  with  the  magnesium  flash- 
light. In  this  way  the  width  of  tin-  pupil  is  recorded  before  it  has 
time  to  alter.  Or  a  longer  exposure  to  ultra-violet  light,  which 
affects  the  pupil  but  little,  may  be  employed.  When  ordinary 
Hght  falls  upon  the  retina  the  pupil  contracts,  and  the  amount  of 
contraction  is  roughly  proportional  to  the  intensity  of  the  light. 
Contraction  of  the  pupil  to  light  is  brought  about  by  a  reflex 
mechanism,  of  which  the  optic  nerve  forms  the  afferent  and  the 
oculo-motor  the  efferent  path,  whilt;  the  centre  is  situated  in  the 
floor  of  the  aqueduct  of  Sylvius.  The  relation  of  this  centre  to 
that  which  controls  the  changes  in  the  pupil  during  accommodation 
has  not  as  yet  been  sufficiently  elucidated;  but  this  we  do  know, 
that  one  of  the  paths  may  be  interrupted  by  disease,  while  the  other 
is  intact.  For  in  tabes  (locomotor  ataxia),  and  in  dementia  para-  ' 
lytica  (general  paralysis),  the  light-reflex  sometimes  disappears, 
while  the  constriction  of  the  pupil  in  accommodation  and  conver- 
gence still  takes  place  (Argyll-Robertson  pupil).  Artificial  stimula- 
tion of  the  optic  nerve  has  the  same  effect  on  the  pupil  as  the 
'  adequate  '  stimulus  of  light;  and  in  many  animals  (including  man), 
though  not  in  those  whose  optic  nerves  completely  decussate,  there 
is  a  consensual  light-refiex — i.e.,  both  pupils  contract  when  one 
retina  or  optic  nerve  is  excited.  This  should  be  remembered  in 
using  the  pupil-reaction  as  a  test  of  the  condition  of  the  retina. 
For  although  the  absence  of  contraction  may  show  that  the  retina 
of  the  eye  on  which  the  light  is  allowed  to  fall  is  insensible  (unless 
there  is  some  physical  hindrance  to  its  passage,  such  as  opacity 
of  the  lens  or  cataract),  the  occurrence  of  contraction  does  not 
exclude  insensibility  of  the  retina  unless  the  other  eye  has  been 
protected  from  the  light. 

Stimulation  of  the  cervical  sympathetic  causes  marked  dilata- 
tion of  the  pupil,  even  when  the  third  nerve  is  excited  at  the  same 
time.  The  pupillo-chlator  fibres  do  not  act  by  constricting  the 
bloodvessels  of  tjie  iris.  For  dilatation  of  tiie  puj)il  can  be  caused 
in  a  bloodless  animal  by  stimulating  tlu'  sympathetic.  .•Xnd  even 
when  the  circulation  is  going  on,  a  short  stimulation  of  the  sympa- 
thetic causes  dilatation  of  the  pupil  without  vaso-constriction. 
while  with  longer  excitation  the  dilatation  of  the  pupil  bt^gins  before 
the  narrowing  of  the  bloodvessels.  Nor  does  it  seem  possible  to 
accept  the  view  that  the  sympathetic  fibres  are  inhibitory  for  the 
sphincter  muscle  of  the  iris.  They  act  directly  upon  dilator  musi'u- 
lar  fibres.  It  has,  indeed,  long  been  known  that  in  the  iris  of  the 
otter  and  of  birds  a  radial  dilator  muscle  exists;  and  it  has  Ixvn 


986  THE  SENSES 

shown  by  Langley  and  Anderson  that  in  the  ins  of  the  rabbit,  cat, 
and  dog,  the  presence  of  radially  arranged  contractile  substance, 
different  it  may  be  in  some  respects  from  ordinary  smooth  muscle, 
must  be  assumed.  Both  the  constrictor  and  the  dilator  muscles 
of  the  iris  are  normally  in  a  condition  of  greater  or  less  tonic  con- 
traction, so  that  the  size  of  the  pupil  at  any  given  moment  depends 
'on  the  play  of  two  nicely  balanced  forces.  Reflex  dilatation  of  the 
pupil  through  the  sympathetic  fibres  is  caused  in  man  by  painful 
stimulation  of  the  skin,  by  dyspnoea,  by  muscular  exertion,  and 
in  some  individuals  even  by  tickling  of  the  palms.  In  animals  the 
stimulation  of  naked  sensory  nerves  has  the  same  effect.  The  '  start- 
ing of  the  eyeballs  from  their  sockets,' which  the  records  of  torture  so 
often  note,  is  due  to  a  similar  reflex  excitation  of  the  sympathetic 
fibres  supplying  the  smooth  muscle  of  the  orbits  and  eyelids. 

Action  of  Drugs  on  the  Function  of  the  Intrinsic  Eye  Muscles. — The 
local  application  of  atropine  causes  temporary  paralysis  cf  accommoda- 
tion and  dilatation  of  the  pupil.  When  the  third  nerve  is  divided,  the 
pupil  dilates ;  it  dilates  still  more  when  atropine  is  administered  after 
the  operation.  Dropped  into  one  eye  in  small  quantity,  atropine  only 
produces  a  local  effect;  the  pupil  of  the  other  eye  remains  of  normal 
size,  or  somewhat  constricted  on  account  of  the  greater  reflex  stimula- 
tion of  its  third  nerve  by  the  greater  quantity  of  light  now  entering  the 
widely-dilated  pupil  of  the  atropinized  eye.  Even  in  the  excised  eye 
the  effect  of  the  drug  is  the  same.  Introduced  into  the  blood  atropine 
causes  both  pupils  to  dilate.  Its  action  is  to  paralyze  the  endings  of 
the  oculo-motor  fibres-  to  the  sphincter  pupilte  and  ciliary  muscle. 
Other  mydriatic,  or  pupil-dilating  drugs,  are  cocaine,  daturine,  and 
hyoscyamine.  Physosiigmine  or  eserine,  pilocarpine,  and  muscarine  are 
the  chief  miotics,  or  pupil-constricting  substances.  They  also  cause 
spasm  of  the  ciliary  muscle,  and  inability  to  accommodate  for  distant 
objects.  They  act  by  stimulating  the  structures  (nerve-endings)  (see 
pp.  i8o,  713)  which  atropine  paralyzes.  The  work  of  the  mydriatics 
can  be  undone  by  the  miotics.  Thus  the  dilatation  produced  by  atro- 
pine is  removed  by  pilocarpine. 

Functions  of  the  Iris. — In  vision  the  iris  performs  two  chief 
functions:  (i)  It  regulates  the  quantity  of  light  allowed  to  fall 
upon  the  retina.  The  larger  the  aperture  of  a  lens,  the  greater  is 
its  collecting  power,  the  more  light  does  it  gather  in  its  focus.  In 
the  eye,  the  area  of  the  pupil  determines  the  breadth  of  the  pencil 
of  light  that  falls  upon  the  lens.  If  this  area  was  invariable,  the 
retina  would  either  be  '  dark  from  excess  of  light  '  in  bright  sunshine, 
or  dark  from  defect  of  hght  in  dull  weather  or  at  dusk.  In  order 
that  the  iris  may  act  as  an  efficient  diaphragm  it  must  be  pig- 
mented, and  it  is  the  pigment  in  it  which  gives  the  colour  to  the 
normal  eye.  The  vision  of  albinos,  in  whose  eyes  this  pigment  is 
wanting,  is  often,  though  not  invariably,  deficient  in  sharpness. 
There  is  always  intolerance  of  bright  light ;  and  the  same  is  true 
in  the  condition  known  as  irideremia,  or  congenital  absence  or 
defect  of  the  iris. 


VISION  987 

(2)  Another,  and  perhaps  equally  important,  function  of  the  iris 
is  to  cut  off  the  more  divergent  rays  of  a  pencil  of  light  falling  upon 
the  eye,  and  thus  to  increase  the  sharpness  of  the  image.  This 
leads  us  to  the  consideration  of  certain  defects  in  the  dioptric 
arrangements  of  the  eye. 

Defects  of  the  Eye  as  an  Optical  Instrument. — (i)  Spherical  Aberra- 
tion.— It  is  a  property  of  a  splieriial  nfracting  sulfate  that  ray.s  of  I 
light  passing  througli  the  periplieral  jiortions  are  more  strongly  refra<  ttil 
than  rays  passing  near  the  principal  axis.  Hence  a  luminous  point 
is  not  focussed  accurately  in  a  single  point  by  a  spherical  lens ;  the  image 
is  surrounded  by  fainter  circles  of  light,  the  so-tailed  circles  of  diffusion 
representing  the  rays  which  have  not  yet  come  to  a  focus,  or  having  been 
already  focussed  have  crossed  and  are  now  diverging.  In  the  eye  this 
spherical  aberration  is  partly  corrected  by  the  interposition  of  the  iris, 
which  cuts  off  the  more  peripheral  rays,  especially  in  actommodat:on 
for  a  near  object,  when  they  are  most  divergent.  In  addition,  the 
anterior  surfaces  of  the  cornea  and  lens  are  not  segments  of  spheres,  but 
of  ellipsoids,  so  that  the  curvature  diminishes  somewhat  with  the  dis- 
tance from  the  optic  axis, 
and,  therefore,  the  re- 
fracting power  as  we  pass 
away  from  the  axis  docs 
not  increase  so  rapidly 
as  it  would  do  if  the 
surfaces  were  truly 
spherical.  Further,  the 
refractive  index  of  the 
peripheral   parts  of  the 

lens  is  less  than  that  of  

its  central  port ions_  Fig.     404.-Spherical     Aberration.     Raj-s     passiug 

(2)    Lnromatic  Aberra-  through  the  more  peripheral  parts  of  a  biconvex 

tion. — All  the  rays  of  the  igng  l  are  brought  to  a  focus  F  nearer  the  lens  than 

spectrum  do    not  travel         F'.  the  focus  of  rays  passing  through  the  central 
with  the   same  velocity         portions  of  the  lens, 
through  a  lens,  and  are, 

therefore,  unequally  refracted  by  it,  the  short  violet  rays  being  focussed 
nearer  the  lens  than  the  long  red  rays.  It  was  at  one  time  supposed  that 
this  chromatic  aberration,  as  it  is  called,  is  compensated  in  the  eye;  and 
it  is  said  that  this  mistake  gave  the  first  hint  that  Newton's  dictum  as 
to  the  proportionality  between  deviation  and  dispersion  was  erroneous, 
and  led  to  the  discovery  of  achromatic  knscs.  But  in  reality  the  eye 
is  not  an  achromatic  combination;  and  the  violet  rays  are  focussed 
about  J  mm.  in  front  of  the  red.  'i  hus.  in  Fig.  405  the  white  light 
passing  through  the  lens  is  broken  up  into  its  constituents:  the  violet 
focus  is  at  V,  and  the  red  at  R,  behind  it.  A  screen  placed  at  R  would 
show  not  a  point  image,  but  a  central  point  surrounded  by  concentric 
circles  of  the  spectral  colours,  with  violet  outside.  If  the  screen  was 
placed  at  V,  the  centre  would  be  violet  and  the  red  would  be  external. 
For  this  reason  it  is  imjxissible  to  focus  at  the  same  time  and  with  jHrfect 
sharpness  objects  of  different  colours:  a  red  light  on  a  railway  track 
appears  nearer  than  a  blue  light,  jiartly  jx>rhaps  for  the  reason  that  it  is 
necessary  to  accommodate  more  strongly  for  the  red  than  for  the  blue, 
and  we  associate  stronger  accommodation  with  shorter  distance  of  the 
object,  although  other  data  are  a'so  involvtil  in  such  a  visual  juilgment. 
When  we  look  at  a  white  gas-flame  through  a  cobalt  glass,  whii  h  allows 
only  red  and  v  olet  to  pass,  we  see  either  a  red  flame,  surrounded  by  a 


988 


THE  SENSES 


violet  ring,  or  a  violet  flame  surrounded  by  a  red  ring,  according  as  we 
focus  for  the  red  or  for  the  violet  rays.  But  the  dispersive  power  of 
the  eye  is  so  small,  and  the  capacity  of  rapidly  altering  its  accommoda- 
tion so  great,  that  no  practical  inconvenience  results  from  the  lack  of 
achromatism,  which,  however,  may  be  easily  demonstrated  by  looking 
at  a  pattern  such  as  that  in  Fig.  406  at  a  distance  too  small  for  exact 
accommodation . 

It  is  also  reckoned  among  the  optical  imperfections  of  the  eye  (3)  that 
the  curved  surfaces  of  the  cornea  and  lens  do  not  form  a  '  centred  '  system 
— that  is  to  say,  their  apices  and  their  centres  of  curvature  do  not  all 
lie  in  the  same  straight  line;  (4)  that  the  pupil  is  eccentric,  being 
situated  not  exactly  opposite  the  middle  of  the  lens  and  cornea,  but 
nearer  the  nasal  side,  and  that  in  consequence  the  optic  axis,  or  straight 
line  joining  the  centres  of  curvature  of  the  lens  and  cornea,  does  not 
coincide  with  the  visual  axis,  or  straight  line  joining  the  fovea  centralis 
with  the  centre  of  the  pupil,  which  is  also  the  straight  line  joining  the 
centre  of  the  pupil  and  any  point  to  which  the  eye  is  directed  in  vision. 
The  angle  between  the  optic  and  visual  axis  is  about  5°  (Fig.  397). 


Fig.  405. — Chromatic  Aberration.  The  violet 
rays  are  brought  to  a  focus  V  nearer  the  lens 
than  R,  the  focus  of  the  red  rays. 


Fig.  406. — To  show  Dispersion  in 
Eye  (v.  Bezold).  View  the 
hgure  from  a  distance  too  small 
for  accommodation.  Approach 
the  eye  towards  it;  the  white 
rings  appear  bluish  owing  to 
circles  of  dispersion  falling  on 
them — i.e.,  circles  of  light  of 
different  colours  due  to  the 
decomposition  of  white  light 
into  its  spectral  constituents  by 
the  media  of  the  eye.  A  little 
closer,  and  the  black  rings  be- 
come white  or  yellowish-white. 


(5)  Muscae  volitantes,  the  curious  bead- 
like or  fibrillar  forms  that  so  often  flit 
in  the  visual  field  when  one  is  looking 
through  a  microscope,  are  the  token  that 
the  refractive  media  of  the  eye  are  not 

perfectly  transparent  at  all  parts ;  they  seem  to  be  due  to  floating  opacities 
.in  the  vitreous  humour,  probably  the  remains  of  the  embryonic  cells  from 
which  the  vitreous  body  was  developed.  (6)  Lastly,  it  may  be  men- 
tioned that  slight  irregularities  in  the  curvature  of  the  lens  exist  in  all 
eyes,  so  that  a  point  of  light,  like  a  star  or  a  distant  street-lamp,  is  not 
seen  as  a  point,  but  as  a  point  surrounded  by  rays  (irregular  astigma- 
tism). In  bringing  this  review  of  the  imperfections  of  the  dioptric 
media  of  the  normal  eye  to  a  close,  it  may  be  well  to  explain  that  what 
are  defects  from  the  point  of  view  of  the  student  of  pure  optics  are  not 
necessarily  defects  from  the  freer  standpoint  of  the  physiologist,  who 
surveys  the  meclianism  of  vision  as  a  whole,  the  relations  of  its  various 
parts  to  one  another  and  to  the  needs  of  the  organism  it  has  to  serve, 
the  long  series  of  developmental  changes  through  which  it  has  come 
to  be  what  it  is,  and  the  possibilities,  so  far  as  we  can  limit  them,  that 
were  open  to  evolution  in  the  making  of  an  eye.  The  optician  may 
perhaps  assert,  and  with  justice,  that  he  could  easily  have  made  a  better 
lens  tlian  Nature  has  furnished,  but  the  physiologist  will  not  readily 
admit  that  he  could  have  made  as  good  an  eye. 


VISION  989 

While  the  defects  hitherto  mentioned  are  shared  in  greater  or 
less  degree  by  every  normal  eye,  there  are  certain  other  defects 
which  either  occur  in  such  a  comparatively  small  number  of  eyes, 
or  lead  to  such  grave  disturbances  of  vision  when  they  do  occur, 
that  they  must  be  reckoned  as  abnormal  conditions.  In  the  normal 
or  emmetropic  eye,  parallel  rays— and  for  this  purpose  all  rays 
coming  from  an  object  at  a  distance  greater  than  65  metres  may  be 
considered  parallel — are  l>roufj;ht  to  a  focus  on  the  retina  without 
any  effort  of  accommodation.  The  distance  at  which  objects  can 
be  distinctly  seen  is  only  limited  by  their  size,  the  clearness  of  the 
atmosphere,  and  the  curvature  of  the  earth;  in  other  words,  the 
punclum  remotum,  or  far-point  of  vision,  the  most  distant  point  at 
which  it  is  possible  to  see  with  distinctness,  is  practically  at  an 
infinite  distance.  When  accommodation  is  paralyzed  by  atropine, 
only  remote  objects  can  be  clearly  seen.  On  the  other  hand,  the 
normal  eye,  or,  to  be  more  precise,  the  normal  eye  of  a  middle-aged 


Fig.  407. — Refraction  in  the  (Mnrmal)  Emmetropic  Eye.  The  image  P'  of  a  distant 
point  P  falls  on  the  retina  when  the  eye  is  not  accommodated.  To  save  space, 
P  is  placed  much  too  near  the  eye  in  Figs.  407,  408. 

adult,  can  be  adjusted  for  an  object  at  a  distance  of  not  more  than 
12  cm.  (or  5  inches).      Nearer  than  this  it  is  not  possible  to  see 
distinctly;  this  point  is  accordingly  called  the   punctum  proximum 
or  near-point.    The   range   of  accommodation   for   distinct   \ision « 
in  the  emmetropic  eye  is  from  12  cm.  to  infinity. 

Myopia,  or  short-sightedness,  is  generally  due  to  the  excessive 
length  of  the  antero-postcrior  diameter  of  the  eyeball  in  relation 
to  the  converging  power  of  the  cornea  and  the  lens.  Even  in 
the  absence  of  accommodation,  parallel  rays  are  not  focussed  on 
the  retina,  but  in  front  of  it ;  and  in  order  that  a  sharp  image  may 
be  formed  on  the  retina  the  object  must  be  so  near  that  the  rays 
proceeding  from  it  to  the  eye  are  sensibly  divergent — that  is  to 
say,  it  must  be  at  least  nearer  than  65  metres — but  as  a  rule  an 
object  at  a  distance  of  more  than  2  to  3  metres  cannot  be  distinctly 
seen.  With  the  strongest  accommodation  the  near-point  may  be 
as  little  as  3  cm.  from  the  eye.     The  range  of  vision  in  the  myopic 


990 


THE  SENSES 


eye  is  therefore  very  small.  The  defect  may  be  corrected  by  con- 
cave glasses,  which  render  the  rays  more  divergent.  It  is  to  be 
noted  that  many  cases  of  internal  squint  in  children  are  connected 
with  myopia,  the  eyes  necessarily  rotating  inwards  as  they  are  made 
to  fix  an  abnormally  near  object.  The  treatment  both  of  the  squint 
and  the  myopia  in  these  cases  is  the  use  of  concave  spectacles 
(Fig.  408).     M3'opia,  although  a  condition  that  shows  a  distinct 


Fig.  408. — Myopic  Eye.  The  image  P'  of  a  distant  point  P  falls  in  front  of  the  retina 
even  without  accommodation.  By  means  of  a  concave  lens  L  the  image  may  be 
made  to  fall  on  the  retina  (dotted  lines). 

hereditary  tendency,  is  rarely  present  at  birth;  the  elongation  of  the 
antero-posterior  diameter  of  the  eyeball  develops  gradually  as  the 
child  grows. 

In  hypermetropia,  or  long-sightedness,  the  eye  is,  as  a  rule,  too 
short  in  relation  to  its  converging  power;  and  with  the  lens  in  the 
position  of  rest,  parallel  raj'S  would  be  focussed  behind  the  retina. 
Accordingly,  the  hypermetropic  eye  must  accommodate  even  for 


Fig.  409. — Hypermetropic  Eye.  The  innage  P'  of  a  point  f  falls  behind  the  retina 
in  the  unaccommodated  eye.  By  means  of  a  convex  lens  L  it  may  be  focussed 
on  the  retina  without  accommodation  (dotted  lines). 

distant  objects,  while  even  with  maximum  accommodation  an 
object  cannot  be  distinctly  seen  unless  it  is  farther  away  than  the 
near-point  of  the  emmetropic  eye.  The  far-point  of  distinct  vision 
is  at  the  same  distance  as  in  the  emmetropic  eye — viz.,  at  infinity — 
the  near-point  is  farther  from  the  eye.  The  defect  is  corrected  by 
convex  glasses  (Fig.  409)  Hypermetropia,  unlike  myopia,  is 
present  at  birth. 


VISION  991 

Presbyopia,  or  the  long-sightedness  of  old  age,  is  not  to  be  con- 
founded with  hypcrmetropia.  It  is  essentially  due  to  failure  in 
the  power  of  accommodation,  chiefly  through  weakness  of  the 
ciliary  muscle,  but  partly  owing  to  increased  rigidity  and  loss  of 
elasticity  of  the  lens.  Images  of  distant  objects  are  still  formed 
on  the  retina  of  the  unaccommodated  eye  with  perfect  sharpness — 
i.e.,  the  far-point  of  vision  is  not  affected.  But  the  eye  is  unable 
to  accommodate  sufhciently  for  the  rays  diverging  from  an  object 
at  the  ordinary  near-point;  in  other  words,  the  near-point  is  farther 
away  than  normal.     Convex  glasses  are  again  the  remedy. 

The  near-point  of  distinct  vision  can  be  fixed  in  various  ways — 
among  others,  by  means  of  Scheiner's  experiment  (Practical 
Exercises,  p.  1060).  Two  pin-holes  are  pricked  in  a  card  at  a  dis- 
tance less  than  the  diameter  of  the  pupil.  A  needle  viewed  through 
the  holes  appears  single  when  it  is  accommodated  for,  double  if  it , 
is  out  of  focus.  The  near-point  of  vision  is  the  nearest  point  at 
which  the  needle  can  still,  by  the  strongest  effort  of  accommoda- 
tion, be  seen  single. 

Astigmatism. — It  has  been  mentioned  that  slight  differences  of 
curvature  along  different  meridians  of  the  refracting  surfaces  exist 
in  all  eyes.  But  in  some  cases  the  difference  in  two  meridians  at 
right  angles  to  each  other  is  so  great  as  to  amount  to  a  serious 
defect  of  vision.  To  this  condition  the  name  of  '  astigmatism  '  or 
'  regular  astigmatism  '  has  been  given.  It  is  usually  due  to  an 
excess  of  curvature  in  the  vertical  meridians  of  the  cornea,  less  fre- 
quently in  the  horizontal  meridians;  occasionally  the  defect  is  in 
the  lens.  Rays  proceeding  from  a  point  are  not  focussed  in  a  point, 
but  along  two  lines,  a  horizontal  and  a  vertical,  the  horizontal 
linear  focus  being  in  front  of  the  other  when  the  vertical  curvature 
is  too  great,  behind  it  when  the  horizontal  curvature  is  excessive. 
The  two  limbs  of  a  cross  or  the  two  hands  of  a  clock  when  Ihey  are 
at  right  angles  to  each  other  cannot  be  seen  distinctly  at  the  same 
time,  although  the}'  can  be  successively  focussed.  The  condition 
may  be  corrected  by  glasses  which  are  segments  of  cylinders  cut 
parallel  to  the  axis  (Practical  Exercises,  p.  1062). 

The  Ophthalmoscope. — The  pupil  of  the  normal  eye  is  dark,  and 
the  interior  of  the  eye  invisible,  without  special  means  of  illu- 
minating it.  But  this  is  not  because  all  tlie  light  that  falls  upon  the 
fundus  is  absorbed  by  the  pigment  of  the  choroid,  for  even  the  pupil 
of  an  albino  appears  dark  when  the  eye  is  covered  by  a  piece  of 
black  cloth  with  a  hole  in  front  of  the  pupil.  The  explanation  is 
as  follows : 

Let  the  raj^s  from  a  luminous  point.  P,  be  focussed  by  the  lens, 
L,  at  P'  (Fig.  410).  It  is  plain  that  rays  proceeding  from  P'  will 
oxor<lv  retrnce  the  path  of  those  from  P  ;Mid  be  focussed  at  P. 
Now,  the  eye  receives  rays  from  all  directions,   and,  when  it  is 


992 


THE  SENSES 


sufficiently  well  illuminated,  sends  rays  out  in  all  directions.  The 
moment,  however,  that  the  observing  eye  is  placed  in  front  of  the 
observed  eye,  the  latter  ceases  to  receive  light  from  the  part  of  the 
field  occupied  by  the  pupil  of  the  former,  and  therefore  ceases  to 
reflect  light  into  it. 

This  difficulty  is  avoided  by  the  use  of  an  ophthalmoscopic 
mirror.     The  original,  and  theoretically  the  most  perfect,  form  of 

such  a  mirror  is  a  plate, 
or  several  superposed 
plates,  of  glass,  from  which 
a  beam  of  light  from  a 
laterally  placed  candle  or 
lamp  is  reflected  into  the 
observed  eye,  and  through 
Fig.  410.  which  the  eye  of  the  ob- 

server looks  (Fig .  411)- 
But  the  illumination  thus  obtained  is  comparatively  faint ;  and  a 
concave  mirror  is  now  generally  used.  In  the  centre  is  a  small 
hole  or  a  small  unsilvered  portion  of  the  mirror  for  the  observer's 
eye.  In  the  direct  method  of  examination  (Fig.  413),  the  mirror 
is  held  close  to  the  observed  eye,  and  an  erect  virtual  image  of 


Fig.  411. — Figure  to  illustrate  the  Principle  of  the  Ophthalmoscope.  Rays  of  light 
from  a  point  P  are  reflected  by  a  glass  plate  M  (several  plates  together  in  Helm- 
holtz's  original  form)  into  the  observed  eye  E'.  Their  focus  would  fall,  as  shown 
in  the  figure,  at  P',  a  little  behind  the  retina  of  E.  The  portion  of  the  retina 
AB  is  therefore  illuminated  by  diffusion  circles;  ar.d  the  rays  from  a  point  of 
it  F  will,  if  E'  is  emmetropic  and  unaccommodated,  issue  parallel  from  E' 
and  be  brought  to  a  focus  at  F'  on  the  retina  of  the  (emmetropic  and  unaccom- 
modated)  observing  eye  E. 

the  fundus  is  seen.  When  the  eye  of  the  observer  and  of  the 
patient  are  both  emmetropic,  and  both  eyes  are  unaccommodated, 
the  rays  of  light  proceeding  from  a  point  of  the  retina  of  the 
observed  eye  are  rendered  parallel  by  its  dioptric  media,  and  are 
again  brought  to  a  focus  on  the  observer's  retina. 

If  the  observed  eye  is  myopic,  the  rays  of  light  coming  from 


VISION 


993 


a  point  of  the  retina  leave  the  eye,  even  when  it  is  unaccommo- 
dated, as  a  convergent  pencil;  and  the  emmetropic  non-accom- 
modated eye  of  the  observer  must  have  a  concave  lens  placed 
before  it  in  order  that  the  fundus  may  be  distinctly  seen. 

When  the  observed  eye  is  hyper- 
metropic, the  rays  emerging  from  the 
unaccommodated  eye  are  divergent, 
and  a  convex  lens,  the  strength  of 
which  is  proportional  to  the  amount 
of  hypermetropia,  must  be  placed 
before  the  observer's  unaccommo- 
dated eye  if  he  is  to  see  the  fundus 
distinctly.  By  accommodating,  the 
observer  can  see  the  fundus  clearly 
without  a  convex  lens. 

By  this  method  errors  of  refraction 
in  the  eye  may  be  detected  and 
measured.  The  observer  must  always 
keep  his  eye  unaccommodated,  and 
if  it  is  not  emmetropic,  he  must 
know  the  amount  of  his  short-  or 
long-sightedness  —  i.e.,  the  strength 
and  sign  of  the  lens  needed  to  correct 
his   defect    of   refraction,    and    must 

allow   for   this   in   calculating   the   defect    of    his    patient.     Non 
accommodation  of  the  eye  of  the  latter  can  always  be  secured  by 
the  use  of  atropine. 


Fig.  412.- 


-May's  Electric  Ophthal 
moscope. 


Fig.  413.  — iJirect  .Method  of  usiny  the  Ophthalmoscope.  Liyht  falliiin  on  the  per 
forated  concave  mirror  M  passes  into  the  observed  eye  E';  and.  both  E'  and  the 
observing  eye  E  being  supposed  emmetropic  and  unaccommodated,  an  erect 
virtual  image  of  the  illuminated  retina  of  E'  is  seen  by  E. 

By  the  direct  method  of  ophthalmoscopic  examination,  t)nlv  a 
small  portion  of  the  retina  can  be  seen  at  a  time,  and  this  is  highly 
magnified.  A  larger,  though  less  magnified,  view  can  be  got  by 
the  indirect  method.     The  observed  eve  is  illuminated  as  before, 


994  THE  SENSES 

but  the  mirror  and  the  observer's  eye  are  at  a  greater  distance 
(Fig.  416).  Here  the  rays  from  a  considerable  portion  of  the 
retina  are  brought  to  a  focus  by  a  convex  lens  held  near  the  eye 
of  the  patient,  so  as  to  form  a  real  and  inverted  aerial  image  of  the 


Fig  414. — Use  of  the  Ophthalmoscope  (Direct  Method)  for  testing  Errors  of  Re- 
fraction in  Myopic  Eye.  Rays  issuing  from  a  point  of  the  retina  of  E',  the 
observed  (myopic  and  unaccommodated)  eye,  pass  out,  not  parallel,  but  con- 
vergent. Tliey  will  therefore  be  focussed  in  front  of  the  retina  of  the  observing 
(unaccommodated)  eye  E  if  the  latter  is  emmetropic.  By  introducing  a  concave 
lens  L  of  suitable  strength,  however,  a  clear  view  of  the  retina  of  E'  will  be 
obtained,  and  the  strength  of  this  lens  is  the  measure  of  the  amount  of  myopia. 

retina.  This  image  is  viewed  by  the  observer  at  his  ordinary  visual 
distance.  It  is  not  necessarj?  in  this  method  that  the  observed 
eye  should  be  non-accommodated,  although  it  is  convenient  as  in 


Fig.  415  Testing  Errors  of  Refraction  in  Hypermetropic  Eye.  Rays  from  a  point 
ol  the  retina  of  E',  the  observed  eye,  issue  divergent,  and  are  focussed  behind 
the  retina  of  the  observing  (unaccommodated  and  emmetropic)  eye  E.  The 
strength  of  the  convex  lens  L,  which  must  be  introduced  in  front  of  E  to  give 
clear  vision  of  the  retina  of  E'.  measures  the  degree  of  hypermetropia. 

the  direct  method  to  cause  dilatation  of  the  pupil  by  atropine,  which 
also  relaxes  the  accommodation  (Practical  Exercises,  p.  1065). 

Skiascopy. — To  a  great  extent  the  ophthalmoscopic  method  of 
measuring  errors  of  refraction  has  been  replaced  by  the  more  modern 


VISION 


99S 


method  of  skiascopy  (shadow  test).  It  depends  upon  the  following 
observation:  When  one  throws  light  from  a  little  distance  with  a 
concave  mirror  into  an  observed  eye  and  then  rotates  the  mirror 
slowly  around  the  long  axis  of  the  handle,  one  sees  that  the  pupil, 
which  at  first  was  completely  illuminated,  becomes  dark  from  one 
side  as  if  covered  by  a  shadow.  This  shadow  will  move  in  the  :amc 
direction  in  which  the  mirror  is  rotated  or  in  the  opposite  direction, 
according  to  whether  the  observer  is  farther  from  the  observed  eye 
than  its  far-point,  or  between  the  eye  and  the  far-point.  If  the 
observer  is  exactly  at  the  far-point,  no  direction  of  movement  of 
the  shadow  can  be  made  out,  but  the  pupil  in  its  whole  extent  is 


Fig.  410. — Indirect  .Method  of  using  the  Ophthalmoscoije.  The  rays  of  light  issuiiR 
from  E',  the  observed  eye,  are  focussed  by  the  biconvex  lens  L.  and  a  real  inverttd 
image  of  a  portion  of  the  retina  of  li'.  magnified  four  or  five  times,  is  formed  in 
the  air  between  the  lens  and  the  observing  eye  E.  This  image  is  viewed  by  E 
at  the  ordinary  distance  of  distinct  vision  (10  to  12  inches).  (The  exaggeration 
of  the  size  of  the  mirror  makes  it  appear  as  if  some  of  the  rays  from  the  lamp 
passed  through  the  lens  before  being  reflected  from  the  mirror.  This  would  not 
be  the  case  in  an  actual  observation.) 

either  illuminated  or  altogether  dark.  In  this  way  the  distance 
of  the  far-point  of  a  myopic  eye  can  be  easily  determined  by  a 
metre  rule,  and  from  this  the  degree  of  myopia.  If  the  far-point 
is  either  too  near,  as  in  strong  myopia,  or  too  distant,  as  in  weak 
myopia  and  emmetropia,  or  behind  the  observed  eye,  as  in  h^-per- 
metropia,  it  can  be  brought  to  a  convenient  distance  by  interposing 
suitable  lenses.  The  observer  then  determines  the  far-point  exactly 
by  moving  his  eye  nearer  to  or  farther  from  the  observed  eye, 
or,  keeping  his  own  eye  fixed,  by  brint^ing  the  far-point  of  the 
observed  eye  to  coincide  with  it  by  inserting  lenses  (Practical 
Exercises,  pp.  1066.  1067). 


996  THE  SENSES 

The  phenomenon  depends  upon  the  interruption  which  the  light  pro- 
ceeding from  the  observed  retina  experiences  first  at  the  margin  of  the 
pupil  of  the  observed  eye,  and  then  at  the  margin  of  the  hole  in  the 
mirror  or  of  the  observer's  pupil.  When  the  mirror  is  rotated,  an  illu- 
minated point  of  the  observed  retina  will  move  in  the  opposite  direction 
over  the  retina.*  The  light  proceeding  from  this  point  when  the 
observed  eye  is  emmetropic  is  so  refracted  by  the  lens  and  cornea  that 
it  leaves  the  eye  as  a  bundle  of  parallel  rays  in  the  direction  of  the 
image  of  the  source  of  light  (L')  (Fig.  417).  If  the  image  of  the  flame 
reflected  by  the  mirror  is  situated  on  the  principal  axis  of  the  observer's 
eye,  and  if  the  pupils  of  observed  and  observer  are  of  equal  size,  all 
the  rays  coming  from  the  observed  retina  will  fall  on  the  observer's 
retina,  and  therefore  the  whole  pupil  of  the  observed  eye  will  appear 
light.  If  the  mirror  is  now  rotated  so  that  the  image  of  the  source  of 
light  moves  away  from  the  principal  axis,  and  the  illuminating  rays  are 
no  longer  in  that  axis,  the  illuminated  point  will  move  in  the  opposite 
direction  from  the  principal  axis,  and  the  light  returning  from  the  pupil 
of  the  observed  eye  will  again  issue  in  the  direction  of  the  image  of  the 


Fig.  417. — Path  of  Rays  in  Skiascopy  (Snellen).  U,  observed  eye;  Be,  eye  of  ob- 
server; Sp,  mirror;  L,  source  of  light;  L',  image  of  the  source  of  light;  A,  A', 
principal  a.Kis;  P,  P',  pupils. 

source  of  light.  It  can  then  happen  that  none  of  the  rays  hit  the 
observer's  pupil,  and  the  observed  pupil  will  appear  entirely  dark.  Or 
the  direction  of  the  rays  may  be  such  that  a  portion  of  them  enters  the 
observer's  pupil,  the  rest  being  interrupted  by  its  border.  In  this  case 
the  part  of  the  observed  pupil  from  which  rays  enter  the  observer's 
pupil  will  appear  light,  while  the  rest  is  dark.  From  Fig.  417  it  can  be 
seen  that  the  light  part  of  the  observed  pupil  is  on  the  opposite  side  of 
the  principal  axis  from  the  image  of  the  source  of  light.  If,  therefore, 
the  image  of  the  source  of  light  moves  to  the  riglit  (by  rotation  of  a 
concave  mirror  to  the  right,  or  rotation  of  a  plane  mirror  to  the  left) 
the  skiascopic  appearance  in  the  observed  pupil  moves  to  the  left — i.e., 
in  the  opposite  direction  to  the  image  of  the  source  of  light. 

If  the  observed  pupil  is  myopic— t.e.,  if  its  far- point  is  between  the 
observer  and  the  observed  eye,  rotation  of  the  mirror  so  far  from  the 
principal  axis  that  only  a  part  of  the  rays  issuing  from  the  observed 
pupil  enter  the  observer's  eye,  will  cause  the  pupil  to  appear  light  only 

•  When  a  concave  mirror  is  rotated  to  the  right,  the  inverted  real  mirror 
image  also  moves  to  the  right,  and  the  illuminated  point  to  the  left.  When 
a  plane  mirror  is  rotated  to  the  right,  the  virtual  mirror  image  moves  to  the 
left,  and  the  illuminated  point  on  the  retina  therefore  to  the  rieht. 


VISION  997 

on  one  side,  and  on  account  of  the  crossing  of  the  rays  tliis  illuminated 
portion  will  be  on  the  same  side  of  the  principal  axis  as  the  image  of 
the  source  of  light  (Fig.  418).  When  the  image  of  the  source  of  light  is 
moved  to  the  right  the  light  area  of  the  observed  pupil  will  also  move 
to  the  right — i.e..  with  rotation  of  a  concave  mirror  in  the  same  direction 
as  the  image  of  the  source  of  light,  and  with  rotation  of  a  plane  mirror 
in  the  opposite  direction  (Snellen). 

A  method  of  photographing  the  retina  in  tlie  living  eye  has  also  been 
employed  as  a  means  of  investigating  the  fundus. 

Single  Vision  with  Both  Eyes — Diplopia. — Schcincr's  experiment  shows 
fliat  it  is  possible  to  have  <loul)lc  vision,  or  diplopia,  with  a  single  eye 
when  two  separate  images  of  the  same  object  fall  upon  different  parts 
of  the  retina.  In  vision  with  both  eyes,  or  binocular  vision,  an  image 
of  every  object  looked  at  is.  of  course,  formed  on  each  retina,  and  we 
have  to  inquire  how  it  is  that  as  a  rule  these  images  are  blended  in 
consciousness  so  as  to  produce  the  perception  of  a  single  object;  and 


A  — 


P' 

Fig.  418. — Path  of  Rays  in  Skiascopy  (Myopic  Eye)  (Snellen).     PR,  far -point  ol 
observed  eye.     The  other  references  are  as  in  Fig.  417. 

how  it  is  that  under  certain  conditions  this  blending  does  not  take 
place,  and  diplopia  results.  Two  chief  theories  have  been  invoked  in 
the  attempt  to  answer  these  questions:  (i)  the  theory  of  identical 
points,  (2)  the  theory'  of  projection. 

In  regard  to  the  second  theory,  we  shall  merely  say  that  it  assumes 
that  in  some  way  or  other  the  retina,  or,  rather,  the  retino-ccrebral 
apparatus,  has  the  power  of  appreciating  not  only  the  shape  and  size 
of  an  image,  but  also  the  direction  of  the  rays  of  light  whii  h  form  it, 
and  that  the  position  of  the  object  is  arrived  at  by  a  process  of  mental 
projection  of  the  image  into  space  along  these  directive  lines.  Where 
the  directive  lines  of  the  two  eyes  cut  each  other,  the  two  images  coin- 
cide, and  the  object  is  seen  single  in  the  jwsition  of  the  jxiint  of  inter- 
section,     rhc  first  theory  wc  sliall  examine  in  some  detail. 

The  Theory  of  Identiceil  Points. — This  thcorN'  assumes  that  every 
point  of  one  retina  '  corresponds  '  to  a  definite  point  of  the  other  retina, 
and  that  in  virtue  of  this  correspondence,  either  by  an  inlx)m  necessity 
or  from  experience,  the  mind  refers  simultaneous  impressions  upon  twc 
corresponding  or  identical  points  to  a  single  point  in  external  space. 
If  we  imagine  the  two  retinae  in  the  position  which  the  eyes  occupy 
when  fixing  an  infinitely  distant  object — that  is,  with  the  visual  axes 
parallel — to  be  superposed,  with  fovea  f)vcr  fovea,  every  point  of  the 
one  retina  will  be  covered  by  the  corrcspKinding  j^xiint  of  tlie  other 
retina,  so  that  identical  points  could  be  pricked  through  with  a  needle. 


998-  THE  SENSES 

But  since  the  actual  centre  of  the  retina  does  not  correspond  with  the 
fovea  centralis  (Fig.  397),  but  lies  nearer  the  nasal  side,  the  nasal  edge 
of  the  left  retina  will  overlap  the  temporal  edge  of  the  right,  and  the 
nasal  edge  of  the  right  will  overlap  the  temporal  edge  of  the  left;  so 
that  a  part  of  each  retina  has  no  corresponding  points  in  the  other. 

The  adherents  of  this  theory  claim,  and  with  justice,  that  a  small 
object  so  situated  that  its  image  must  be  formed  on  corresponding 
points  of  the  two  retinae  does,  as  a  rule,  appear  single,  and,  what  is  even 
more  striking,  that  a  phosphene,  or  luminous  ring  produced  by  pressing 
the  blunt  end  of  a  pencil  or  the  finger-nail  on  a  point  of  the  globe  of  one 
eye  (which  Newton  compared  to  the  circles  on  a  peacock's  tail),  is  not 
doubled  by  pressure  over  the  corresponding  point  of  the  other  eye, 
although  two  circles  are  seen  when  pressure  is  made  upon  points  which 
do  not  correspond.  If  in  rotating  the  eyes  one  eye  is  prevented  by 
pressure  with  the  finger  from  following  the  movement  of  the  other, 
there  is  double  vision.  When  strabismus  or  squinting  is  produced  by 
paralysis  of  the  third  (p.  895)  or  the  sixth  cranial  nerve  (p.  897),  it  is 
accompanied  by  diplopia,  until  in  course  of  time  the  mind  learns  to 
disregard  one  of  the  images.  In  some  cases  of  squint  the  double  images 
are  never  completely  suppressed,  but  a  new  abnormal  form  of  visual 
localization  is  developed,  which,  however,  very  seldom  permits  any 
accurate  judgment  of  depth.  In  strabismus  it  is  obvious  that  the  two 
images  of  an  object  cannot  fall  on  corresponding  points. 

But  it  is  also  a  fact  that,  under  certain  conditions,  images  situated 
on  corresponding  points  may  not,  and  that  images  not  situated  on 
corresponding  points  may,  give  rise  to  a  single  impression.  For  ex- 
ample, if  one  of  the  closed  eyes  be  held  slightly  out  of  its  ordinary 
position  by  the  finger,  pressure  on  identical  points  of  the  two  eyes  gives 
rise  to  two  separate  phosphenes.  And  some  of  the  phenomena  of  stere- 
oscopic vision  (p.  999)  show  clearly  that  images  falling  on  points  not 
strictly  corresponding  may  give  a  single  impression;  while  we  do  not 
habitually  see  double,  although  it  is  certain  that  the  images  of  multi- 
tudes of  objects  are  constantly  falling  on  points  of  the  retinae  not  ana- 
tomically '  identical.'* 

The  question  therefore  arises.  How  is  it  that  we  do  not  sec  these 
double  images?  This  is  one  of  the  difficulties  of  the  theory  of  identical 
points.  The  following  is  a  partial  explanation:  (i)  The  images  of 
objects  in  the  portion  of  the  field  most  distinctly  seen — that  is,  the 
portion  in  the  immediate  neighbourhood  of  the  intersection  of  the 
visual  lines,  or  the  part  to  which  the  gaze  is  directed — are  formed  on 
identical  points;  and  by  rapid  movements  the  eyes  fix  successively 
different  parts  of  the  field  of  view.  (2)  Vision  grows  less  distinct  as 
we  pass  out  from  the  centre  of  the  retina,  and  we  are  accustomed  to 
neglect  the  blurred  peripheral  images  in  comparison  with  those  formed 

♦  In  every  fixed  position  of  the  eyes,  the  objects  whose  images  fall  on 
corresponding  points  will  be  arranged  on  certain  definite  lines  or  surfaces 
which  vary  with  the  direction  of  the  visual  axis  and  to  which  the  name  of 
horopter,  or  point-horopter,  has  been  given.  For  most  eyes  when  directed 
to  the  horizon — that  is,  with  the  visual  axes  parallel — -the  horopter  is  practi- 
cally the  horizontal  plane  of  the  ground,  so  that  all  objects  within  the  field 
of  vision,  and  resting  on  the  ground,  fall  upon  corresponding  points,  and  are 
seen  single.  When  the  eyes  are  directed  to  a  point  at  such  a  distance  that 
the  lines  of  vision  are  sensibly  convergent,  the  horopter  consists  (i)  of  a 
straight  line  drawn  through  the  fixing-point  and  at  right  angles  to  a  plane 
passing  through  the  fixing-point  and  the  two  visual  lines  (visual  plane) ;  (2)  of 
a  circle  pas.sing  through  the  fixing-point  and  the  nodal  points  of  the  two  eyes 
(the  famous  horopteric  circle  of  Miiller). 


VISION 


9S9 


on  the  fovea.  (3)  When  the  images  of  an  object  do  not  fall  on  identical 
points,  one  of  tlic  points  on  which  they  do  f<ill  may  be  occupied  with 
the  images  of  other  objects,  some  of  wliich  may  be  so  boldly  marked 
as  to  enter  into  conflict  with  the  extra  image  and  to  suppress  it. 
(4)  Lastly,  the  physiological  '  identical  po=nt  ' '  is  not  a  ger  metrical 
point,  but  an  area  which  increases  in  size  in  trie  more  peripheral  zones 
of  the  retina,  and  can  also  be  increased  by  practice;  and  images  which 
lie  wholly  or  in  chief  part  witiiin  two  corresponding  areas  practically 
coincide. 

Stereoscopic  Vision. — Although  the  retinal  image  is  a  projection  of 
external  ol)j(.(  Is  on  a  surface,  we  perceive  not  only  the  length  and 
breadth,  but  also  the  depth  or  solidity  of  the  things  we  look  at.  When 
we  look  directly  at  the  front  of  a  build- 
ing, the  impression  as  to  its  form  is  the 
same  whether  one  or  both  eyes  be  used, 
although  witli  a  single  eye  its  distanc 
cannot  be  judged  so  accurately.  But 
when  we  view  the  building  from  such  a 
position  that  one  of  the  comers  is  visil)lc, 
we  obtain  a  more  correct  impression  of 
its  depth  with  the  two  eyes.  This  is 
partly  due  to  the  fact  that  to  fix  points 
at  different  distances  from  the  eyes  the 
visual  lines  must  be  made  to  converge 
more  or  less,  and  of  the  amount  of  this 
convergence  we  are  conscious  through 
the  contraction  of  the  muscles  which 
regulate  it.  But  there  is  another  elemc  nt 
involved.  When  the  two  eyes  look  at  a 
uniformly -coloured  plane  surface,  the 
retinal  image  is  precisely  the  same  in 
both.  But  when  the  two  eyes  arc 
directed  to  a  solid  object  (say  a  book 
lying  on  a  table)  the  picture  formed  on 
the  left  retina  differs  slightly  from  that 
formed  on  the  right,  for  the  left  eye  sees 
more  of  the  left  siele  of  the  book,  and 
the  right  eye  more  of  the  right  side. 

That  there  is  a  close  connection  be- 
tween uniformit)'  of  retinal  images  and 
impression  of  a  plane  surface  on  the  one 
hand ,  anel  difference  of  retinal  images  and 
impression  of  solidity  on  the  other,  is 
proved  by  the  facts  of  stcreoscopy.  It 
is  evielent  that  if  an  exact  picture  of  the  solid  object  as  it  is  seen  by 
each  eye  can  be  thrown  on  the  retina,  the  impression  produced  will 
be  the  same,  whether  tiiese  images  are  really  fonncd  by  the  object 
or  not.  Now,  two  such  picturc^s  can  be  produced  with  a  near  approach 
to  accuracy  by  photographing  the  object  from  the  point  of  view  of 
each  eye.  It  only  remains  to  cast  the  image  of  each  picture  on  the 
corresponding  retina,  while  the  eyes  are  converged  tc  the  same  extent 
as  wouUl  be  the  case  if  they  were  viewing  the  actual  object.  This  is 
accomplishcel  by  means  e.f  a  stereoscope  (Fig.  419). 

It  is  found  that  the  re'sultant  impression  is  that  of  the  solid  object. 
It  is  impossible  to  reconcile  this  with  the  doitrine  of  strictlv  identical 
geometrical  points.  A  pair  of  iilentical  pictures  gives  with  the  stere- 
oscope not  the  impression  of  a  soliel,  but  of  a  plane  suifacc.      If  the 


Fig.  419. — Brewster's  Stereoscope. 
p  and  TT  are  prisms,  with  their  re- 
fracting angles  turned  towards 
each  other.  The  prisms  refract 
the  rays  coming  from  the  points 
c.  y  of  the  pictures  ab  and  a/i  so 
that  they  appear  to  come  from  a 
single  point  </.  Similarly,  the 
points  a  and  (p  appear  to  be  situ- 
ated at/,  and  the  points  b  and  /3. 
at  a. 


looo  THE  SENSES 

relative  position  of  any  two  points  differs  in  the  two  pictures,  the 
blended  picture  has  a  corresponding  point  in  rehef.  So  great  is  the 
delicacy  of  this  test  that  a  good  and  a  bad  banknote  will  not  blend 
under  the  stereoscope  to  a  fiat  surface,  and  the  method  may  be  actually 
used  for  the  detection  of  forger}^ 

When  the  pictures  are  interchanged  in  the  stereoscope  so  that  the 
image  which  ought  to  be  formed  on  the  right  retina  falls  on  the  left,  and 
that  which  is  intended  for  the  left  eye  falls  on  the  right,  what  were 
projections  before  become  hollows,  and  what  were  hollows  stand  out 
in  relief.  The  pseudoscope  of  Whcatstone  is  an  arrangement  by  which 
each  eye  sees  an  object  by  reflection,  so  that  the  images  which  would  be 
formed  on  the  two  retina?,  if  the  object  were  looked  at  directly,  are  inter- 
changed, with  the  same  reversal  of  our  judgments  of  relief. 

Visual  Judgments. — We  say  judgments  of  relief;  for  what  we  call 
seeing  is  essentially  an  act  that  involves  intellectual  processes.  As  the 
retina  is  anatomically  and  developmentally  a  projection  of  the  brain 
pushed  out  to  catch  the  waves  of  light  which  beat  in  upon  the  organism 
from  every  side,  so,  physiologically,  retina,  optic  nerve,  and  visual 
nervous  centre  are  bound  together  in  an  indissoluble  chain.  We 
cannot  say  that  the  retina  sees,  we  cannot  say  that  the  optic  nerve 
sees — the  optic  nerve  in  itself  is  blind — we  cannot  say  that  the  visual 
centre  sees.  The  ethereal  waves  falling  on  the  retina  set  up  impulses 
in  it  which  ascend  the  optic  nerve;  certain  portions  of  the  brain  are 
stirred  to  action,  and  the  resulting  sensations  of  light  springing  up,  we 
know  not  where,  arc  elaborated,  we  know  not  how  (by  processes  of 
which  we  have  not  the  faintest  guess),  into  the  perception  of  what  we 
call  external  objects — trees,  houses,  men,  parts  of  our  own  bodies,  and 
into  judgments  of  the  relations  of  these  things  among  themselves,  of 
their  distance  and  movements. 

A  child  leams  to  see,  as  it  learns  to  speak,  by  a  process,  often  un- 
conscious, or  subconscious,  of  '  putting  two  and  two  together.'  The 
musical  sounds  united  and  terminated  by  noises  which  make  up  the 
spoken  word  '  apple  '  are  gradually  associated  in  its  mind  with  the 
visual  sensation  of  a  red  or  green  object,  the  tactile  sensation  of  a 
smooth  and  round  object,  and  the  gustatory  and  olfactory  sensations 
which  we  call  the  taste  or  flavour  of  an  apple.  And  as  it  is  by  ex- 
perience that  the  child  learns  to  label  this  bundle  of  sensations  with  a 
spoken,  and  afterwards  with  a  written,  name,  so  it  is  by  experience 
tk.at  it  learns  to  group  the  single  sensations  together,  and  to  make  the 
induction  that  if  the  hand  be  stretched  out  to  a  certain  distance  and  in 
a  certain  direction — i.e,  if  various  muscular  movements,  also  associated 
with  sensations,  be  made — the  tactile  sensation  of  grasping  a  smooth 
round  body  will  be  felt,  and  that  if  the  further  muscular  movements 
involved  in  conveying  it  to  the  mouth  be  carried  out,  a  sensation  agree- 
able to  the  youthful  palate  will  follow.  At  length  the  child  comes  to 
believe,  and,  unless  he  happens  to  be  specially  instructed,  carries  his 
belief  with  him  to  his  grave^  that  when  he  looks  at  an  apple  he  sees  a 
round,  smooth,  tolerably  hard  body,  of  definite  size  and  colour;  while, 
in  reality  all  that  the  sense  of  sight  can  inform  him  of  is  the  difference 
in  the  intensity  and  colour  of  the  light  falling  on  his  retina  when  he 
turns  his  head  in  a  particular  direction. 

An  interesting;  illustration  of  the  role  of  experience  in  shaping 
our  visual  judgments  is  found  in  the  sensations  of  persons  born 
blind  and  relieved  in  after-life  by  operation.  A  boy  between 
thirteen   and  fourteen  years  of  age,   operated  on   by  Cheselden, 


VISION 


lOOI 


thought  all  the  objects  he  looked  at  touched  his  eyes.  *  He  forgot 
which  was  the  dog  and  which  the  cat,  but  catching  the  cat  (which 
he  knew  by  feeling),  he  looked  at  her  steadfastly  and  said,  "  So, 
puss,  I  shall  know  you  another  time."  Pictures  seemed  to  him  only 
parti-coloured  planes;  but  all  at  once,  two  months  after  the  opera- 
tion, he  discovered  they  represented  solids.'  Nunnely,  perhaps 
remembering  the  dictum  of  Diderot,  that  '  to  prepare  and  interro- 


Fig.  420. — Illusion  of  Parallel  Lines  (Hering). 

gate  a  person  born  blind  would  not  have  been  an  occupation  un- 
worthy of  the  united  talents  of  Newton,  Des  Cartes,  Locke,  and 
Leibnitz,'  made  an  elaborate  investigation  in  the  case  of  a  boy  nine 
years  old,  on  whom  he  operated  for  congenital  cataract  of  both  eyes, 
and,  what  is  of  special  importance,  instituted  a  set  of  careful 
experiments  and  interrogations  before  the  operation,  so  as  to  gain 
data  for  comparison.  Objects  (cubes  and  spheres)  which  before 
the  operation  he  could  easily  recognize  by  touch  were  shown  hirr 
afterwards,  but  al- 
though '  he  could  at 
once  perceive  a  differ- 
ence in  their  shapes, 
he  could  not  in  the 
least  say  which  was 
the  cube  and  which 
the  sphere.'  It  took 
several  days,  and  the 
objects  had  to  be 
placed  many  times  in 
his    hands    before    he  Fig,  421.  — illusion  u£  rarallcl  Lwus  (ZoUncr). 

could    tell    them    by 

the  eye.  '  He  said  everything  touched  his  eyes,  and  walked  most 
carefully  about,  with  his  hands  held  out  before  him  to  prevent 
things  hurting  his  eyes  by  touching  them.' 

Many  other  illustrations  might  be  given  of  the  fact  that  '  seeing  ' 
is  largely  an  act  of  reasoning  from  data  which  may  sometimes 
mislead.  Thus  in  Figs.  420  and  421  the  long  horizontal  lines  are 
really  parallel,  but  do  not  appear  so  owing  to  the  confusion  of 
judgment  produced  by  the  short  sloping  lines.  In  Fig.  422  the 
spaces  covered  by  A,  B,  and  C  are  equal  squares,  but  A  appears 


/////////////////// 


THE  SENSES 


<"    > 


taller  than  B,  and  C  smaller  than  either  A  or  B.  In  the  same 
figure  the  lines  D  and  E  are  of  the  same  length,  but  E  seems  con- 
siderably longer  than  D. 

Illusions  of  movement  are  among  the  most  interesting  optical 
illusions.  If  two  similar  objects  are  momentarily  shown  to  the 
eye  in  rapid  succession  and  at  points  in  space  not  separated  by  too 
great  a  distance,  the  illusion  is  produced  that  the  first  object  has 
moved  to  the  position  of  the  second.  Such  illusions  are  the  basis 
of  the  so-called  '  moving  pictures  '  shown  by  the  cinematograph. 
A  series  of  instantaneous  photographs  of  a  movement  are  taken, 
recording  the  successive  positions  assumed  by  the  moving  body. 
When  these  are  thrown  on  the  retina  in  the  same  order  and  in  rapid 
succession,  an  illusion  of  the  original  movement  is  produced. 

The  apparent  size  and  form  of  an  object  is  intimately  related  to 
the  size,  form,  and  sharpness  of  its  image  on  the  retina.     We  are, 

therefore,  able  to  dis- 
A  h  C  criminate  with  great 

precision      the     un- 
stimulated from  the 
excited    portions    of 
that  membrane,   es- 
pecially in  the  fovea 
centralis,    and    also 
the  degree  of  excita- 
tion of  neighbouring 
excited    parts.     But 
instead  of  locaHzing  the  image  on  the  retina  as  we  localize  on  the 
skin  the  pressure  of  an  object  in  contact  with  it,  we  project  the 
retinal  image  into  space,  and  see  everything  outside  the  eye. 

In  vision,  in  fact,  we  have  no  conception  of  the  existence  of  either 
retina  or  retinal  image;  and  even  the  shadows  of  objects  within  the 
eye — for  instance,  an  opacity  or  a  foreign  body  in  any  of  the  refractive 
media — are  referred  to  points  outside  it.  Generally  opacities  in  the 
vitreous  humour  are  movable,  in  the  lens  not. 

Purkinje's  Figures. — As  was  first  pointed  out  by  Purkinje,  the 
shadows  of  the  bloodvessels  in  the  retina  itself,  and  even  of  the 
corpuscles  circulating  in  them,  although  neglected  in  ordinary 
vision,  may  be  recognized  under  suitable  conditions,  a  conclusive 
proof  that  the  sensitive  layer  must  lie  behind  the  vessels. 

If  a  beam  of  sunlight  is  concentrated  on  the  sclerotic  as  far  as  possible 
from  the  margin  of  the  cornea,  and  the  eye  directed  to  a  dark  ground, 
the  network  of  retinal  bloodvessels  will  stand  out  on  it.  Another 
method  is  to  look  at  a  dark  ground  while  a  lighted  candle,  held  at  one 
side  of  the  eye  at  a  distance  from  the  visual  line,  is  moved  slightly  to 
and  fro.  In  the  first  method,  a  point  of  the  sclerotic  behind  the  lens 
is  illumimted,  and  rays  passing  from  it  across  the  interior  of  the  eyebcill 
in  every  direction  cast  shadows  of  the  vessels  of  the  retina  on  its  sensi- 


< 


Fig.  422. — Illusions  of  Space-Perception. 


VISION 


1003 


tive  layer.  In  the  second  mctho<l,  the  image  of  the  flame  formed  on 
the  retina  by  rays  falling  obli^jucly  tiirougli  the  pupil  becomes  in  the 
general  darknc-ss  itscll  a  source  of  light,  by  interrupting  the  rays  from 
which  the  retinal  vessels  form  shadows.  The  flistancc  of  the  sensitive 
from  the  vascular  layer  may  be  approximately  calculated  by  measuring 
the  amount  by  which  the  shadows  change  their  position,  when  the 
position  of  the  illuminated  point  of  the  sclerotic  is  altered.  The  nearer 
a  vessel  lies  to  the  sensitive  layer,  the  smaller  must  be  the  angle  through 
which  the  apparent  position  of  its  shadow  moves  for  a  given  move- 
ment of  the  spot  of  light.  In  this  way  it  has  been  calculated  that  the 
sensitive  layer  is  about  o-j  to  0-3  mm.  behind  the  stratum  which  con- 
tains the  bloodvessels. 
This  corresponds  suffi- 
ciently well  with  the 
position  of  the  layer  of 
rods  and  cones,  which  all 
other  evidence  shows  to 
be  the  portion  of  the 
retina  actuallv  stimulatcil 
by  light.  The  shadows  of 
the  blood -corpuscles  in 
the  retinal  vessels  may  be 
rendered  visible  by  look- 
ing at  a  bright  and  uni- 
fonnlyilluminalcdground, 
like  the  milk  glass  shade 
of  a  lamp  or  the  blue  sky, 
and  moving  the  slightly 
separated  fingers  or  a 
perforated  card  rapid  )>■ 
before  the  eye.  From  the 
rate  of  their  apparent 
movement,  Vierordt  cal- 
culated the  velocity  of  the 
blood  in  the  retinal  capil- 
laries at  0'5  to  0'9  mm. 
per  second.  One  reason 
why  the  shadows  of  these 
intra-retinal  structures  do 


Fig.  .(.Zj.  Motli  id  of  rendering  the  Retinal  Rlood- 
\-cssels  visible  by  concentrating  a  Beam  of  Light 
on  the  Sclerotic.  From  the  brightly-illuminated 
point  of  the  sclerotic,  a.  rays  issue,  and  a  shadow 
of  a  vessel,  v,  is  cast  at  a'.  It  is  referred  to  an 
external  point,  a',  in  the  direction  of  the  straight 
line  joining  a'  with  the  nodal  point.  When  the 
light  is  shifted  so  as  to  be  focussed  at  b,  the 
shadow  cast  at  b'  is  referred  to  b' — i.e.,  it  appears 
to  move  in  the  same  direction  as  the  illuminated 
point  of  the  sclerotic. 


not  appear  in  ordmary 
vision  seems  to  be  their  small  size.  The  retinal  vessels  are  in  reality 
only  vascular  threads;  the  thickest  branch  of  the  central  vein  is  not 
.,'.-  mm.  in  diameter.  The  apex  of  the  cone  of  complete  shadow 
(umbra)  cast  by  a  disc  of  this  size,  at  a  distance  of  20  mm.  from  a  punil 
4  mm.  wide,  would  lie  only  \  mm.  behind  the  disc  -that  is  to  say,  the 
umbra  of  the  retinal  vessels  would  not  reach  the  layer  of  the  rixls  and 
cones  at  all,  and  only  tiie  penumbra,  or  region  of  relati\e  darkness, 
would  fall  upon  it. 

When  the  eyes,  after  being  closed  for  some  time,  are  suddenly  opened, 
the  branches  of  the  retinal  vessels  may  be  seen  for  a  moment.  This  is 
especially  the  case  after  sleep;  and  a  good  view  of  the  phenomenon 
may  be  obtained  by  looking  at  a  white  pillow  or  tlie  ceiling  immediately 
on  awaking.  If  the  eyes  are  kept  open  for  a  few  seconds,  the  branch- 
ing pattern  fades  away;  if  they  are  only  allowed  to  remain  open  for 
an  instant,  it  may  be  seen  many  times  in  succession.  Tiie  main  vessels 
appear  to  radiate  out  from  a  central  point.  Hut  their  actual  junction 
there  is  not  seen,  since  it  lies  in  the  optic  disc  or  blind  spot. 


I004 


THE  SENSES 


The  Blind  Spot. — The  fibres  of  the  optic  nerve  are  insensible  to 
light;  light  only  stimulates  them  through  their  end-organs.  This 
can  be  proved  by  directing  by  means  of  an  ophthalmoscope  a  beam 
of  light  upon  the  optic  disc,  where  the  true  retinal  layers  do  not 
exist.  The  person  experimented  on  has  no  sensation  of  light  when 
the  beam  falls  entirely  upon  the  disc ;  when  its  direction  is  shifted 
so  that  it  impinges  upon  any  other  portion  of  the  retina,  a  sensation 
of  light  is  at  once  experienced.  The  Wind  spot  is  not  recognized 
in  ordinary  vision,  for  (i)  the  two  optic  discs  do  not  correspond. 

The  left  disc  has  its  corre- 
sponding points  on  a  sensitive 
part  of  the  right  retina,  and 
the  right  disc  on  a  sensitive 
part  of  the  left  retina;  and  the 
consequence  is  that  in  binoc- 
ular vision  the  objects  whose 
images  are  formed  on  the  cor- 
responding points  fill  up  the 
blind  spots.  (2)  The  optic 
disc  does  not  lie  in  the  line  of 
direct,  and  therefore  distinct, 
vision.  The  eye  is  constantly 
moving  so  as  to  bring  the 
surrounding  objects  succes- 
sively on  the  fovea  centralis; 
and  the  gap  which  the  blind 
spot  makes  in  the  visual  field 
of  a  single  eye  is  thus  more 
easily  neglected.  In  any  case 
we  ought  not  to  see  it  as  a 
dark  spot,  for  darkness  is  only  associated  with  the  absence  of 
excitation  in  parts  of  the  retina  capable  of  being  excited  by  hght. 
There  is  no  more  reason  why  the  optic  discs  should  appear  dark 
than  there  is  for  our  having  a  sensation  of  darkness  behind  us  when 
we  are  looking  straight  in  front.  And  since  the  experience  of  our 
other  senses — the  sense  of  touch,  for  example — tells  us  that  the 
objects  we  look  at  do  not  in  general  have  a  gap  in  the  position  corre- 
sponding to  the  part  of  the  image  that  falls  on  the  bUnd  spot,  we 
see,  so  to  speak,  across  the  spot. 

By  Mariotte's  experiment,  however,  the  existence  of  the  blind  spot 
can  not  only  be  demonstrated,  but  its  size  determined  and  its  bounaaries 
mapped  out.  Let  the  left  eye  be  closed,  and  fix  with  the  right  the  small 
cross ;  then,  if  the  eye  be  moved  towards  or  away  from  the  paper,  keeping 
the  cross  fixed  all  the  time,  a  position  will  be  found  in  which  the  white 
disc  disappears  altogether.  In  this  position  its  image  falls  on  the 
blind  spot  (Fig.  425). 


Fig.  424. — Method  of  rendering  the  Blood- 
vessels of  the  Retina  visible  by  Oblique 
Illumination  through  the  Cornea.  Light 
from  a  candle  at  a  illuminates  a',  and 
rays  proceeding  from  a'  cast  a  shadow  of 
the  bloodvessel,  v,  at  a",  which  is  referred 
to  a"'.  When  a  is  moved  to  b,  the 
shadow  on  the  retina  moves  to  b',  and 
the  shadow  in  the  visual  field  of  the  illu- 
minated eye  to  b'". 


VISIO\  1005 

Relation  of  the  Rods  and  Cones  to  Vision. — We  have  more  than 
once  referred  to  the  rods  and  cones  as  the  sensitive  layer  of  the 
retina.  It  is  now  ncctssary  to  develop  a  little  more  the  evidence 
in  favour  of  this  statement.  And  at  the  outset,  since  the  sensitive- 
layer  has  been  shown  to  lie  behind  the  plane  of  the  retinal  blood- 
vessels, the  only  competitors  of  the  rods  and  cones  are  the  external 
nuclear  layer  and  the  pigmented  epithelium.  The  nuclear  layer 
may  be  at  once  excluded  as  a  separate  mechanism,  since,  as  we  have 
seen  (p.  978),  the  portions  of  the  rod  and  cone  elements  in  it  are 
continuous  with  the  portions  in  the  layer  of  the  rods  and  cones 
proper.  In  the  fovea  centralis,  where  vision  is  most  distinct,  the 
nuclear  layer  becomes  very  thin  and  inconspicuous. 

The  layer  of  pigmented  hexagonal  cells,  or  at  hast  their  pigment, 
cannot  be  essential  to  vision,  for  albino  rats,  rabbits,  and  men,  in 
whose  eyes  pigment  is  absent,  can  see.  In  man  and  most  mammals 
there  are  cones,  but  no  rods  in  the  yellow  spot  and  fovea  centralis; 
the  relative  proportion  of  rods  increases  as  we  pass  out  from  the 
fovea  towards  the  ora  serrata.     But  this  does  not  enabl^'  us  to 


Fig.   425. — Mariotte's   Experiment. 

analyze  the  bacillary  layer  into  sensitive  cones  and  non-sensitive 
rods,  for  on  the  rim  of  the  retina,  which  is  still  sensitive  to  light, 
there  are  only  rods;  in  the  bat  and  mole  there  are  said  to  be  no 
cones  even  in  the  yellow  spot,  in  the  rabbit  very  few.  Reptiles 
possess  only  cones  over  the  whole  retinal  surface,  and  birds,  true 
to  their  reptilian  affinities,  have  everywhere  more  cones  than  rods, 
as  have  also  fishes. 

One  of  the  difficulties  in  the  way  of  understanding  how  a  ray  of 
light  can  set  up  an  excitation  in  a  rod  or  cones  is  the  transparencv 
of  these  structures.  An  absolutely  transparent  substance — that 
is,  a  substance  which  would  allow  light  to  traverse  it  without  the 
least  absorption — would,  after  the  passage  of  a  ray,  remain  in 
precisely  the  same  state  as  before;  its  condition  could  not  be 
altered  by  the  passage  of  the  light  unless  some  of  the  energy  of  the 
ethereal  vibrations  was  transferred  to  it.  But  an  absolutely  trans- 
parent body  does  not  exist  in  Nature;  and  it  is  not  necessary  to 
suppose  that  all  the  energy  required  to  stimulate  the  end-organs 
of  the  optic  nerve  comes  from  the  luminous  vibratitnis.  Tlu^e 
may,  and  probably  do,  act  by  setting  free  energy  stored  up  in  the 


ioo6  THE  SENSES 

retina,  just  as  the  touch  of  a  child's  hand  could  be  made  to  fire  a 
mine,  or  launch  a  ship,  or  flood  a  province.  Some  have  looked  upon 
the  transverse  lamellae  into  which  the  outer  members  of  the  rods 
and  cones  can  be  made  to  split  as  an  arrangement  for  reflecting 
back  the  light  to  the  inner  members,  and  have  compared  them 
to  a  pile  of  plates  of  glass,  which,  transparent  as  it  is,  is  a  most 
efficient  reflector.  It  is  even  possible,  although  here  we  are  already 
treading  the  thin  air  of  pure  speculation,  that  the  light  may  be 
polarized  in  the  process  of  reflection,  and  that  the  rods  and  cones 
may  be  less  transparent  to  light  polarized  in  certain  planes  than  to 
unpolarized  light. 

As  to  the  nature  of  the  transformation  undergone  by  the  ethereal 
vibrations  in  the  rods  and  cones,  various  theories  have  been  formu- 
lated. Some  have  supposed  that  the  absorbed  light-waves  are 
transformed  into  long  heat-waves,  and  that  the  endings  of  the  optic 
nerve  are  thus  excited  by  thermal  stimuH.  This  hypothesis  has  so 
little  evidence  in  its  favour  that  it  is  perhaps  an  unjustifiable  waste 
of  time  even  to  mention  it.  It  is  ruled  out  of  court  by  the  mere  fact 
that  the  long  radiations  of  the  ultra  red,  filtered  from  luminous  rays 
by  being  passed  through  a  solution  of  iodine,  and  focussed  on  the 
eye  by  a  lens  of  rock-salt,  produce  not  the  slightest  sensation  of 
light,  although  they  are  by  no  means  all  absorbed  in  their  passage 
through  the  dioptric  media.  Again,  it  has  been  suggested  that  the 
energy  of  the  waves  of  light  is  first  transformed  into  electrical  energy, 
and  that  the  visual  stimulus  is  really  electrical.  In  support  of 
this  view  it  has  been  urged  that  the  passage  of  a  voltaic  current 
through  the  eye  causes  sensations  of  light,  and  that  light,  un- 
doubtedly, causes  (p.  8ii)  an  electrical  change  in  the  retina  and 
optic  nerve.  But,  as  has  more  than  once  been  pointed  out,  an 
electrical  change  is  the  token  and  accompaniment  of  the  activity 
of  the  excitable  tissues  in  general;  and  all  that  the  currents  of 
action  of  the  retina  show  is  that  light  excites  the  retina — a  proposi- 
tion which  nobody  who  can  see  requires  an  objective  proof  of,  and 
which  does  not  carry  us  very  far  towards  the  solution  of  the 
problem  how  that  excitation  is  brought  about.  Then  there  is 
the  photo-mechanical  theory,  according  to  which  the  pigmented 
epithelial  cells  of  the  retina,  altering  their  shape  and  volume  under 
the  stimulus  of  light,  press  upon  the  rods  and  cones,  and  thus 
mechanically  stimulate  them.  Lastly,  there  is  the  photo-chemical 
theory,  which  supposes  that  some  chemical  change  produced  in  the 
rods  and  cones  under  the  influence  of  light  sets  up  impulses  in  them 
which  ascend  the  optic  nerve.  This  is  the  most  probable  of  all  the 
theories,  notwithstanding  the  fact  that  the  discovery  by  Boll  of 
the  famous  visual  purple  or  rhodopsin,  which  at  first  seemed  likely 
to  place  it  upon  a  sure  foundation,  has  lost  its  significance  in  this 
regard.     But  although  the  visual  purple  is  not  a  photo-chemical 


VISION 


1007 


substance  through  which  the  retinal  elements  are  excited  by 
luminous  stimuli,  it  seems  to  fulfil  an  important  functicm  in  adapt- 
ing the  retina—/.^.,  rendering  it  more  sensitive — for  visi<jn  in  dim 
light.  In  any  case,  its  discovery  is  in  itself  so  interesting  and  so 
suggestive  as  a  basis  for  future  work,  that  a  short  account  of  the 
properties  of  the  substance  cannot  be  omitted  here. 

Visual  Purple. — If  tlie  eye  of  a  frop;  or  rabbit,  whicli  lias  been  kept 
in  tlie  dark,  be  cut  out  in  a  dimly-lighted  chamber  or  in  a  chamber 
illuminated  only  by  red  light,  and  the  retina  removed,  it  is  seen,  when 
viewed  in  ordinary  light,  to  be  of  a  beautiful  red  or  purple  colour. 
Exposed  to  bright  light,  the  colour  soon  fades,  passing  through  red  and 
orange  to  yellow,  and  then  disappearing  altogether.  The  yellow  colour 
is  due  to  the  formation  of  another  pigment,  visual  yellow;  the  preceding 
stages  are  due  to  the  intermixture  of  this  visual  yellow  with  the  un- 
changed visual  purple  in  different  proportions.  With  the  microscope 
it  may  be  seen  that  the  pigment  is  entirely  confined  to  the  outer  segment 
of  the  rods,  where  it  exists  in  most  vertebrate  animals.  It  may  be  ex- 
tracted by  a  watery  solution  of  bile-salts,  and  the  properties  of  the 
pigment  in  solution  are  very  much  the  same 
as  its  properties  in  silu  ;  light  bleaches  the 
solution  as  it  does  the  retina.  Examined  with 
the  spectroscope,  the  solution  shows  no  definite 
bands,  but  only  a  general  absorption,  which  is 
very  slight  in  the  red,  and  reaches  its  ma.xi- 
mum  in  the  yellowish-green.  In  accordance 
with  this,  it  is  found  that  of  all  kinds  of  mono- 
chromatic light  the  yellowish-green  rays  bleach 
the  purple  most  rapidly,  the  red  rays  most 
slowly. 

If  a  portion  of  the  retina  is  kept  dark  while 
the  rest  is  exposed  to  light,  only  the  latter 
portion  is  bleached.  And  when  the  image  of 
an  object  possessing  well-marked  contrasts  of 
light  and  shadow  {e.g.,  a  glass  plate  with  strips 
of  black  paper  pasted  on  it  at  intervals,  or  a 
window  with  dark  bars)  is  allowed  to  fall  on  an 
eye  otherwise  protected  from  light,  the  pattern 
of  the  object  is  picked  out  on  the  retina  in 
purple  and  white.  A  veritable  photograph  or  '  optogram  '  may  thus  be 
formed  even  on  the  retina  of  a  living  rabbit;  and  if  the  eye  be  rapidly 
excised,  the  picture  may  be  '  fixed  '  by  a  solution  of  alum,  and  thus 
rendered  permanent. 

These  facts  certainly  suggest  that  light  falling  on  the  retina  may 
cause  in  some  sensitive  substance  or  substances  chemical  changes, 
the  products  of  which  stimulate  the  endings  of  the  optic  nerve, 
and  set  up  the  impulses  that  result  in  visual  sensations. 

The  visual  purple  cannot  itself  be  such  a  substance,  for  it  is 
absent  from  the  cones  of  all  animals  and  the  rods  of  some.  Frogs 
and  rabbits  can  undoubtedly  see  at  a  time  when,  by  continued 
exposure  to  bright  sunlight,  the  purple  must  have  been  completely 
bleached.  And  although  the  allegetl  absence  of  the  pigment  in 
the  eye  of  the  bat  might  seem  to  afford  a  ready  explanation  of  the 


Fig.  426. — Optogram.  Part 
of  retina  of  rabbit,  the 
eye  of  which  had  been 
directed  to  an  illumin- 
ated plate  of  glass  cov- 
ered with  strips  of  black 
paper. 


ioo8  THE  SENSES 

proverbial  '  blindness  '"  of  that  animal,  such  a  hasty  deduction 
would  be  at  once  corrected  by  the  fact  that  birds  with  as  sharp 
vision  as  the  pigeon  are  equally  devoid  of  visual  purple,  while  in 
other  nocturnal  animals,  like  the  owl,  it  is  plentifully  found.  The 
most  probable  hypothesis  of  the  function  of  the  visual  purple  is 
indeed  that  which  attributes  to  it  the  property,  in  virtue  of  its 
capacit}'  for  regeneration  in  the  dark,  of  adapting  the  eye  for  night 
or  twilight  vision — in  other  words,  of  increasing  the  sensitiveness 
of  the  retina  for  faint  light,  especially  of  the  shorter  wave-lengths. 
If  this  is  the  case,  it  is  precisely  in  nocturnal  animals  that  we  should 
expect  to  find  it  in  large  amount ;  and  recently  visual  purple  has 
been  obtained  from  more  than  one  species  of  bat  (Trendelenburg). 
The  fact  that  central  vision  (p.  1018)  in  which  the  rodless  fovea  is 
concerned  is  but  little,  if  at  all,  susceptible  of  dark-adaptation, 
while  peripheral  vision  shows  a  marked  capacity  of  adaptation, 
agrees  well  with  this  hypothesis.  We  shall  see  later  that  there  is 
some  evidence  that  it  is  the  mere  perception  of  luminous  impressions 
as  such  and  of  their  intensity,  without  any  distinction  of  quality 
or  colour,  with  which  the  rods  have  to  do.  They  are,  then,  on  the 
hypothesis  under  discussion,  elements  concerned  in  achromatic 
sensations  under  conditions  of  feeble  illumination  (twilight  vision). 
The  cones  are  supposed  on  this  theory  to  be  more  highly  developed 
elements  than  the  rods,  their  function  being  connected,  especially 
with  the  perception  of  colour,  but  also  with  the  perception  of 
achromatic  sensations  under  daylight  conditions. 

The  pigmented  retinal  epithelium  is  undoubtedly  sensitive  to  light, 
and  has  important  relations  to  the  formation  of  the  visual  purple. 
Wlien  the  eye  is  exposed  to  light,  black  pigment  migrates  along  the 
processes  of  the  epithelial  cells  between  the  rods,  even  as  far  as  the 
external  limiting  membrane.  In  the  dark  the  pigment  moves  back 
again,  and  gathers  around  the  outer  portions  of  the  rods,  where  the 
visual  purple  is  being  regenerated.  The  precise  meaning  of  the  changes 
in  the  pigmented  cells  is  obscure. 

The  pigmented  epitheUum  is  known  to  be  concerned  in  the  regenera- 
tion of  the  visual  purple.  When  a  frog  is  curarized,  oedema  occurs 
between  the  retina  and  the  choroid,  so  that  the  former  membrane  is 
separated  from  the  hexagonal  epithelium.  If  the  frog  is  now  exposed 
to  sunlight  till  the  visual  purple  is  bleached,  and  the  retina  then  taken 
out  and  placed  in  the  dark,  no  regeneration  of  the  purple  takes  place. 
When  the  same  experiment  is  repeated  on  a  non-curarized  frog,  the 
visual  purple  is  restored  in  the  dark,  and  may  be  seen  under  the  micro- 
scope in  the  rods.  The  only  difference  in  the  two  experiments  is  that 
in  the  latter  the  pigmented  epithelium  adheres  to  the  retina,  and  it 
must  therefore  have  a  hand  in  the  regeneration  of  the  pigment.  Even 
the  visual  purple  of  a  retina  from  which  the  epithelium  has  been  de- 
tached will,  after  being  bleached,  be  restored  if  the  retina  is  simply  laid 
again  on  the  epithelial  surface.  And  it  does  not  seem  to  be  the  black 
pigment  of  the  hexagonal  cells  which  is  the  agent  in  this  restoration, 
for  it  takes  place  in  the  pigment-free  retinae  of  albino  rabbits  or  rats. 
Even  a  retina  isolated  from  the  pigmented  epithelium,  and  then 
bleached,  may,  to  a  certain  extent,  develop  new  visual  purple  in  the 


VISION  1005 

dark.  This  is  even  true  when  it  has  been  kept  in  the  dark  in  a  saturated 
sohition  of  sodium  chloride,  and  is  then,  after  wasliing  with  physio- 
logical salt  solution,  bleached  by  light.  Here  the  regeneration  of  the 
pigment  cannot  be  the  result  of  vital  processes,  but  must  be  due  to 
chemical  changes  in  products  formed  from  the  original  jjigment  by  the 
action  of  light.  No  such  regeneration  takes  place  in  a  retina  which, 
after  having  been  bleached  m  situ,  is  removed  without  the  pigmented 
epithelium  and  placed  in  the  dark;  and  the  only  probable  explanation 
of  the  difference  is  that  in  this  case  the  photo-chemical  substances 
from  which  visual  purple  can  be  formed  have  been  absorbed  into  the 
circulation,  and  liavc  so  escaped. 

The  inner  segments  01  the  cones  of  certain  animals  (birds,  reptiles, 
amphibia,  and  some  fishes)  contain  globules  of  various  colours,  ranging 
over  almost  the  whole  sjx-ctrum,  and  incluiiing,  besides,  the'non -spectral 
colour,  purple.  The  globules  are  composed  chiefly  of  fat  with  the 
pigments  (chromophancs,  as  they  have  been  called)  dissolved  in  it. 
The  function  of  these  globules  is  unknown.  They  cannot  be  concerned 
in  colour  vision,  or,  at  least,  they  cannot  be  essential  to  it,  for  in  the 
human  retina  they  do  not  exist. 

The  yellow  pigment  of  the  macula  lutea  does  not  belong  to  the  layer 
of  rods  and  cones;  it  only  exists  in  the  external  molecular  layer  and  the 
layers  in  front  of  it;  in  llic  fovea  centralis  it  is  absent. 

Time  necessary  for  Excitation  of  the  Retina  by  Light— Fusion  of 
Stimuli. — Whatever  the  exact  nature  of  retinal  excitation  may  be, 
it   is   called    forth    by  exceedingly  slight   stimuli.     A   lightning  flash, 

although  it  may  last  only th  of  a  second,  lasts  long  enough 

'=>■'■'    1,000,000  "  ° 

to  be  seen.     A  beam  of  light  thrown  from  a  rotating  mirror  on  the 

eye  stimulates  when  it  only  acts  for  „ th  of  a  second.     The 

■'  8,000,000 

minimum  stimulus  in  the  form  of  green  light  corresponds,  as  we  have 

already  seen   (p.  758),  to  a  quantity  of  work  equivalent  to  no  more 

than  8  erg — that  is,  about  — ^-^  gramme-millimetre,  or  -.,  milli- 
gramme-millimetre,   which    is  the   work   done    by    th   of  a 

■'    10,000,000 

milligramme  in  falling  through  a  millimetre;  and  it  cannot  be  doubted 
that  a  portion  even  of  this  Lilliputian  bombardment  is  wasted  as  heat. 
So  quickly,  too,  is  the  stimulus  followed  by  the  response  that  no  latent 
period  has  as  yet  ever  been  measured.  It  is  certain,  however,  that 
there  is  a  latent  period,  as  surely  as  there  is  a  latent  period  in  the 
excitation  of  a  naked  nerve-trunk,  although  this  also  has  never  been 
experimentally  detected.  The  analogies,  in  fact,  between  a  muscular 
contraction  and  a  retinal  excitation  are  numerous  and  close.  Like  the 
muscle,  the  retina  seems  to  possess  a  store  of  explosive  material  which 
the  stimulus  serves  only  to  fire  off.  The  retina,  like  the  muscle,  is 
exhausted  by  its  activity,  and  recovers  during  rest.  Like  the  muscle 
curve,  the  curve  of  retinal  excitation  rises  not  abruptly,  but  with  a 
measurable  slowness  to  its  height,  and  when  stimulation  is  stopped, 
takes  a  sensible  time  to  fall  again,  the  retinal  impression  outlasting  the 
luminous  stimulus  by  about  onc-uighth  of  a  second.  With  compara- 
tively slow  intermittent  stimuli  the  retinal,  like  the  muscle  curve, 
flickers  up  and  down.  When  the  rate  of  stimulation  is  increased,  the 
steady  contraction  of  the  tetanized  mu.-^cle  is  analogous  to  the  fusion 
of  the  individual  stinuili  by  the  tetanizcfl  retina  (or  retino-cerrbral 
apparatus)  into  a  continuous  sensation  of  light,  such,  e.g.,  as  the  bright 

04 


loio  THE  SENSES 

'  trail  '  of  a  falling  star,  or  the  fiery  circle  traced  in  the  air  when  a  fire- 
brand is  rapidly  whirled  round.  But  the  maximum  retinal  excitation 
which  a  stimulus  of  given  strength  can  call  forth  depends  much  more 
closely  upon  the  time  during  which  the  stimulus  acts  than  the  maximum 
contraction  does  upon  the  length  of  the  muscular  stimulus. 

As  the  strength  of  the  light  increases  in  geometrical  progression,  the 
time  during  which  it  must  act  in  order  to  produce  its  maximum  effect 
decreases  approximately  in  arithmetical  progression  (Exner).  For  light 
of  moderate  intensity  this  time  is  about  ^  second.  Since  for  complete 
fusion  the  stimuli  must  follow  each  other  at  a  much  more  rapid  rate 
than  four  in  the  second,  the  intensity  of  the  resultant  sensation  is 
always  less  when  a  succession  of  similar  stimuli  are  fused  than  when  one 
of  the  stimuli  is  allowed  to  produce  its  maximum  effect. 

If  the  time  of  each  stimulus  is  equal  to  the  interval  during  which 
there  is  no  stimulation,  the  sensation,  when  complete  fusion  has  been 
reached,  is  the  same  as  would  be  produced  by  a  constant  light  of  half 
the  strength  employed.  And,  in  general,  if  m  be  the  proportion  of  the 
time  during  which  the  eye  is  stimulated  by  a  light  of  intensity  /,  and  n 
the  proportion  of  the  time  during  which  it  is  not  stimulated,  the  resultant 
impression  is  the  same  as  that  which  would  be  produced  by  an  un- 

~~~  17.     This  is  Talbot's  law,  which 

may  be  expressed  without  the  aid  of  symbols  thus:  When  a  light  of 
given  intensity  is  allowed  to  act  on  the  eye  at  intervals  so  short  that  the 
impressions  are  completely  fused,  the  resultant 
sensation  is  independent  of  the  absolute  length  of 
each  flash,  and  is  proportional  only  to  the  fraction 
of  the  whole  time  which  is  occupied  by  flashes  and 
to  the  intensity  of  the  light.  Talbot's  law  may  be 
readily  demonstrated  by  means  of  a  rotating  disc 
with  alternate  white  and  black  sectors  (Fig. 
427),  so  arranged  that  the  same  proportion  of  the 
circumference  of  each  of  the  three  concentric 
zones  is  black. 

When  the  rotation  is  sufficiently  rapid  to  give 

Pig    427. — Disc  for  de-     complete  fusion  (say  20  to  30  times  a  second), 

monstrating    Talbot's     the  whole  disc  appears  equally  bright.    However 

law.  much  the  rate  of  rotation  is  now  increased,  no 

further  change  occurs.     It  has  been  shown  that 

even  for  stimuli  as  short  as  the   Kooooon'th  of  a  second,  repeated   at 

intervals  of  Y^o't'i  second,  Talbot's  law  holds  good.      So  that  not  only 

does  a  flash   so  inconceivably  brief  affect  the   retina,  but  it    sets  up 

changes  which  last  for  a  measurable  time.      For  intense  stimuli  Talbot's 

law  ceases  to  be  true:   the  field  appears  brighter  than  it  should  be 

(Griinbaum). 

Two  chief  theories  have  been  proposed  to  account  for  the  fusion  of 
intermittent  retinal  stimuli:  (i)  The  persistence  theory,  according  to 
which  the  excitatory  process  in  the  retina  remains  for  a  short  time  at 
the  maximum  reached  when  the  light  ceases  to  act.  Steady  fusion  is 
supposed  to  be  obtained  when  the  interval  between  successive  stimuli 
does  not  exceed  this  time.  (2)  The  theory  of  Fick,  who  maintains  that 
as  soon  as  the  light  is  withdrawn  the  retinal  excitation  begins  to  sink, 
at  first  rapidly,  then  more  gradually.  As  the  rate  of  stimulation  is 
increased  the  time  allowed  for  the  decline  of  the  excitation  is,  of  course, 
correspondingly  shortened,  and  ultimatclv  the  oscillations  become  so 
small  that  a  continuous  smooth  sensation  results.  Fick's  theory 
appears  to  explain  the  phenomena  best. 


VISION  loil 

1  he  experiments  of  Charpentier  have  shown  tliat  the  retina  wiien 
stimulated  has  a  natural  tcndoncy  to  enter  int<j  oscillatif)ns  at  the  rate 
of  about  30  in  the  second,  so  tliat  the  effect  of  a  Hash  of  li^ht  when  it 
falls  on  a  retinal  area  is  not  a  sin^^de  excitation  wiiich  rises  smootidy  to 
its  maximum  and  then  declines  smoothly  to  zero,  but  a  scries  of  swings 
which  die  away  like  the  vibrati(>ns  of  an  elastic  body.  This  may  be 
demonstrated  by  slowly  rotating  a  well-illuminated  disc,  one  quadrant 
of  which  is  white  and  the  rest  black,  while  the  eye  is  kept  fixed  on  the 
centre.  A  black  band,  or  rather  sector,  running  out  from  centre  to 
circumference,  will  be  seen  in  the  white  quadrant  a  little  behind  the 
border  of  it  which  first  passes  the  eye.  This  band  may  be  succeeded  by 
one  or  more  fainter  black  bands  placed  at  regular  intervals  in  the  white 
portion  of  the  disc.  The  explanation  is  this.  At  the  moment  when  the 
image  of  the  advancing  edge  of  the  white  cpiadrant  falls  upon  the 
retina  it  is  excited,  and  we  get  the  sensation  of  white.  Then  comes  a 
swing  in  the  opposite  direction  which  gives  rise  to  the  first  black  band, 
and  succeeding  swings  cause  the  other  bands.  The  period  of  the  oscil- 
latory process  can  be  calculated  from  the  speed  of  the  disc,  anrl  the 
distance  of  the  first  band  from  the  edge  of  the  white  quadrant.  The 
well-known  fact  that  a  single  flash  of  lightning,  or  other  intense  stimulus, 
may  appear  „s  two  flashes,  finds  its  explanation  in  these  retinal  oscilla- 
tions. 

Colour  Vision. — Besides  differences  in  the  distance,  size,  shape, 
and  brightness  of  objects,  the  eye  recognizes  differences  in  their 
colour;  and  we  have  now  to  consider  the  physical  and  physiological 
differences  on  which  these  depend. 

Colours  may  differ  from  each  other — (i)  In  tone  or  hue,  e.g.,  red, 
yellow,  green.  (2)  In  degree  of  saturation  or  fulness  or  purity,  i.e.,  in 
the  degree  in  which  they  are  free  from  admixture  with  white  light,  e.g., 
a  '  pale  '  or  '  light  '  blue  is  a  blue  mixed  with  much  white  light,  a  '  deep  ' 
or  '  full  '  blue  with  kttle  or  none.  (3)  In  brightness  or  intensity,  i.e.,  in 
the  amount  of  the  light  coming  from  unit  area  of  the  coloured  object. 
Thus,  a  '  dark  '  red  cloth  sends  comparatively  little  light  to  the  eye,  a 
'  bright  '  red  cloth  sends  a  great  deal. 

When  a  beam  of  sunlight  falls  into  the  eye,  a  sensation  of '  white 
light  '  results.  When  a  prism  is  placed  before  the  eye,  the  sensation 
is  entirely  different ;  we  sec  a  spectrum  running  up  from  red  through 
green  to  violet,  with  a  multitude  of  intermediate  shades,  the  eye 
being  able  to  distinguish  in  the  solar  spectrum  at  least  one  thousand 
different  hues  (Aubcrt).  What,  then,  has  happened  ?  Physically, 
nothing  more  has  taken  place  than  a  rearrangement  of  the  rays 
in  the  beam  of  white  light.  A  few  of  them  may  have  been  lost  by 
reflection,  but  upon  the  whole  the  beam  is  made  up  of  exactly  the 
same  constituents  as  before;  only  the  rays  are  now  arranged  in  the 
precise  order  of  their  refrangibihty,  the  more  refrangible,  which  are 
also  those  of  shortest  wave-length,  being  displaced  more  towards  the 
base  of  the  prism  than  the  longer  and  less  refrangible  rays.  In- 
stead of  the  long  and  short  rays  falling  together  on  the  same  ele- 
ments of  the  retina,  as  they  did  in  the  absence  of  the  prism,  they 
now  fall,  if  proper  precautions  have  been  taken  to  secure  a  pure 
spectrum,  in  regular  order  from  one  side  to  the  other  of  the  portion 


10I2  THE  SENSES 

of  retina  on  which  the  image  is  formed.  The  physical  condition, 
then,  of  our  sensations  of  the  prismatic  colours  is,  that  rays  of 
approximately  the  same  wave-length  should  fall  unmixed  with 
other  rays  upon  the  retinal  elements.  Rays  of  a  wave-length  of 
760  ^f^*  to  6^0/Liju  give  the  sensation  of  red;  from  650  jujli  to  590  juju, 
the  sensation  of  orange;  from  430  juju  to  400  juju,  the  sensation  of 
violet,  and  so  on.  When  raj^s  of  all  these  wave-lengths  fall  together, 
in  the  proportion  in  which  they  are  present  in  sunlight,  upon  the 
same  part  of  the  retina,  the  resultant  physiological  effect  is  very 
different ;  we  are  no  longer  able  to  distinguish  red,  blue,  green,  etc. ; 
we  receive  the  single  sensation  of  white  light.  The  sensation  is  a 
simple  one;  in  consciousness  we  have  no  hint  that  it  has  a  multiple 
physical  cause. 

But  we  find  further  that  it  is  not  necessary  for  the  sensation  of 
white  light  that  waves  of  every  length  present  in  the  solar  spectrum 
should  be  mixed.  If  rays  of  wave-lengths  675  /li/u  (which  acting 
alone  produce  the  sensation  of  red)  be  mixed  in  certain  proportions 
— i.e.,  be  allowed  to  fall  on  the  same  part  of  the  retina — with  rays 
of  wave-length  496  /j,ju  (which  give  the  sensation  of  bluish-green), 
the  resultant  sensation  is  also  that  of  white  light.  And  an  in- 
definite number  of  sets  can  be  combined,  two  and  two,  so  as  to  give 
the  same  sensation  of  white.  Such  colours  are  called  comple- 
mentary.    The  following  are  pairs  of  complementary  colours: 

Red  and  bluish-green.  Yellow  and  ultramarine-blue. 

Orange  and  cyan-blue,  f  Greenish-yellow  and  violet. 

The  green  of  the  spectrum  has  no  simple  complementary  colour; 
purple,  a  colour  not  present  in  the  spectrum,  but  obtained  by 
mixing  light  from  the  two  spectral  extremes — i.e.,  by  mixing  red 
and  violet — may  be  considered  complementary  to  it.  Suppose  now 
that  one  of  a  pair  of  complementary  colours  is  added  to  the  other 
in  greater  intensity  than  is  required  to  give  white,  the  resultant 
sensation  is  a  colour  which  has  a  certain  amount  of  resemblance  both 
to  white  and  to  the  colour  present  in  excess.  Thus,  if  the  two 
colours  are  orange  and  blue,  and  the  blue  is  present  in  greater  in- 
tensity than  is  necessary  to  give  white,  the  resultant  colour  is  a 
whitish  or  pale  blue,  or,  to  use  the  technical  phrase,  an  unsaturated 
blue.  The  more  nearly  the  intensity  of  the  blue  rays  in  the  mixed 
light  approaches  the  proportion  necessary  to  give  white,  the  less 
saturated  is  the  resultant  colour;  the  greater  the  excess  of  blue, 
the  more  nearly  does  the  resultant  sensation  approach  that  of  the 
saturated  blue  of  the  spectrum.  But  any  non-saturated  spectral 
colour  produced  by  the  mixture  of  two  complementary  colours  may 
be  equally  well  produced  by  the  mixture  of  the  corresponding 
spectral  colour  with  a  certain  quantity  of  ordinary  white  light. 

*  fi/x  is  a  symbol  representing  one-millionth  of  a  millimetre. 
t  Cyan-blue  is  a  greenish-blue. 


VISION  1 013 

And  it  is  found  that  when  two  spectral  colours  which  arc  not  com- 
plementary are  mixed  together  the  resultant  is  not  white,  but  a 
colour  which  may  be  matched  by  some  spectral  colour  lying  between 
the  two  (or  by  purple),  either  without  addition  or  plus  a  larger  or 
smaller  quantity  of  ordinary  white  light.  From  all  this  it  follows 
that  the  retina  may  be  excited  by  an  infinite  number  of  different 
physical  stimuli,  and  yet  the  resultant  sensation  may  be  the  same. 
This  leads  straight  to  the  conclusion  that  somewhere  or  other  in 
the  retino-cerebral  apparatus  simplification,  or  synthesis,  of  im- 
pressions must  take  place;  and  we  have  to  inquire  what  the  simplest 
assumptions  are  which  will  explain  all  the  phenomena.  Now,  it  is 
not  possible,  from  two  spectral  colours  alone,  to  produce  a  sensation 
corresponding  to  all  the  others.  By  mixing  three  standard  spectral 
colours,  however,  in  various  proportions,  we  can  produce  not  only 
the  sensation  of  white  light,  but  that  of  every  colour  of  the  spectrum 
(and  of  purple).  These  statements  are  based  on  demonstrated  facts 
obtained  by  very  numerous  experiments  on  colour  mixtures.  The 
hypotheses  framed  to  explain  the  facts  are  to  be  carefully  dis- 
criminated from  the  facts  themselves. 

Primary  Colours. — The  simplest  assumption  we  can  make,  then, 
is  that  there  are  three  standard  sensations,  and  that  either  the 
retina  itself  can  respond  by  no  more  than  three  distinct  modes  of 
excitation  to  the  multiplex  stimuH  of  the  luminous  vibrations,  or 
that  complex  impulses  set  up  in  the  retina  are  reduced  to  simplicity 
because  the  central  apparatus  is  capable  of  responding  by  only 
three  distinct  kinds  of  sensation.  Whicht  hree  sensations  we  select 
as  fundamental  or  primary  is,  to  a  certain  extent,  arbitrary,  pick 
chose  red,  green,  and  blue;  most  commonly  red,  green,  and  violet 
are  accepted  as  the  primary  colours.  Red,  yellow,  and  blue, 
although  so  long  considered  the  primary  colours,  from  data  \nelded 
by  the  mixture  of  pigments,  will  not  do;  for  no  possible  combination 
of  them  will  jModuce  cither  a  pure  green  or  white  light. 

The  Young-Helmholtz  Theory. — The  theory  which  has  been  most 
widely  accepted  is  tliat  of  Young,  generally  called,  on  account  of 
its  adoption  and  extension  by  Helmholtz,  the  Young-Helmholtz 
theory.  Red,  green,  and  violet  are  taken  as  the  fundamental  or 
elementary  colour  sensations.  In  its  more  modern  form  it  assumes 
that  in  the  retina,  or  in  the  retino-cerebral  apparatus,  there  are 
three  kinds  of  elements — (i)  a  substance  or  a  component  chiefly 
affected  by  light  of  comparatively  long  wave-length  (nnl),  to  a  less 
extent  by  liglit  of  medium  wave-length  (green),  and  to  a  still  less 
extent  by  the  shortest  visible  waves  (violet) ;  (2)  a  component  mainly 
affected  by  medium,  but  also  to  a  certain  extent  by  long  and  short 
waves;  (3)  a  component  chiefly  affected  by  the  short  vibrations, 
less  by  the  medium,  and  still  less  by  the  long  waves.  The  curves 
in  Fig.  428  illustrate  these  relations. 


IOI4 


THE  SENSES 


The  theory  explains  as  follows  the  phenomena  of  colour- mixture 
referred  to  above.  When  all  the  rays  of  the  spectrum  act  upon 
the  retina  together,  the  three  components  are  about  equally  affected, 
and  this  equal  effect  is  supposed  to  be  the  condition  of  the  sensation 
of  white  light.  When  the  green  of  the  spectrum  alone  falls  on  the 
retina,  the  '  green  '  component  is  strongly  excited,  the  other  two 


Fig.  428. — Curves  of  Excitability  of  Primary  Sensations  from  Observations  o;i 
Colour  Mixtures  (Konig).  The  numbers  give  wave-lengths  of  the  spectrum  in 
millionths  of  a  millimetre. 

only  slightly;  this  is  the  relation  between  the  amount  of  excitation 
in  the  three  components  which  is  associated  with  a  sensation  of 
spectral  green.  When  two  complementary  colours,  such  as  red  and 
bluish-green,  fall  together  on  the  same  portion  of  the  retina,  the 
three  components  are  excited  in  the  relative  proportions  associated 
with  the  sensation  of  white  light. 

The  colour  triangle  is  a  graphic  method  of  representing  various  facts 
in  colour-mixture  (Fig.  429). 

The  chief  points  to  be  noted  are  the  following:   (i)   On  the  curve 

the  spectral  colours  are 
arranged  at  such  dis- 
tances that  the  angle  con- 
tained between  straight 
lines  drawn  from  the 
point  marked  '  white,' 
and  intersecting  the 
curve  at  the  positions 
corresponding  to  any  two 
colours  is  proportional  to 
their  difference  in  tone. 
(2)  The  distance  of  any 
point  of  the  curve  from 
the  point  marked 'white' 
is  proportional  to  the  stimulation  intensity  of  the  colour  corresponding 
to  it.  (If  the  stimulation  intensities  of  all  the  colours  be  represented  by 
proportional  weights  lying  at  the  corresponding  points  on  the  curve,  the 


Fig.  429. — Colour  Triangle. 


VISION  roi5 

point '  white '  will  be  the  centre  of  gravity  of  the  system.)  (3)  The  position 
of  a  colour  produced  by  the  mixture  of  any  pair  of  sj^ectral  colours  is 
found  by  joining  the  corresponding  points  by  a  straight  line.  1  he  mixed 
colour  lies  on  this  line  at  distances  from  the  two  points  invcrselv  propor- 
tional to  the  stimulation  intensity  of  the  two  colours  — i.e.,  it  lies  in  the 
centre  of  gravity  of  the  weights  representing  the  twocolours.  (4)  It  is  a 
particular  case  of  (3)  that  the  complementary  colours  are  situated  at 
the  points  whcie  straight  lines  drawn  through  '  white  '  intersect  the 
curve,  since  the  point  marked  '  white  '  is  the  centre  of  gravity  corre- 
sponding to  a  jjair  of  colours  only  when  it  lies  on  the  straight  line 
joining  them.  Ihus  the  orange  and  yellow  lying  between  the  red  and 
green  are  mixtures  of  the  red  and  green  sensations  in  dilferent  propor- 
tions; the  cyan-blue  and  indigo-blue  are  mixtures  of  the  green  and 
violet  sensations.  The  purples,  represented  by  a  broken  line,  are  not 
present  in  the  spectrum,  and  are  mixtures  of  red  and  violet. 

It  is  a  point  of  great  tlieorctical  interest  that  on  the  Voung-Helm- 
holtz  theory  the  pure  spectral  colours,  although  physically  saturated 
{i.e.,  due  to  ethereal  vibrations  of  a  definite  wave-length  for  each 
colour),  ought  not  to  be  physiologically  saturated,  since  they  all  afTect 
the  three  components,  although  in  different  degrees.  In  other  words, 
the  red,  let  us  say,  of  the  spectrum  ought  not  to  be  the  purest  or  fullest 
red  which  it  is  possible  to  perceive.  Now,  it  is  found  that  this  is  really 
the  case.  If,  for  example,  we  look  first  at  the  bluish-green,  and  then 
at  the  red  of  the  sp)ectrum,  tlie  sensat-ion  of  red  is  fuller  or  more  saturated 
than  if  we  had  looked  at  the  red  directly.  Similarly,  if  we  look  first  at 
a  small  bluish-green  square  on  a  black  ground,  and  then  at  a  red  ground, 
we  see  a  more  fully  saturated  square  in  the  middle  of  tlie  latter.  The 
explanation,  on  the  Young-Helmholtz  theory,  is  that  the  '  green  ' 
component,  being  fatigued  before  the  eye  is  turned  upon  the  red,  the 
latter  colour  no  longer  affects  it,  or  affects  it  less  than  it  would  other- 
wise do,  and  therefore  the  excitation  is  almost  entirely  confined  to  the 
red  component  in  the  area  fatigued  for  green.  This  brings  us  to  the 
subject  of  retinal  fatigue,  and  the  related  phenomena  of  after-images 
and  contrast. 

After-images. — We  have  seen  that  the  retinal  excitation  always  takes 
time  to  die  away  after  the  stimulus  is  removed.  If  a  white  object  is 
looked  at,  especially  when  the  eye  is  fresh,  for  a  time  not  long  enough 
to  cause  fatigue,  and  the  eye  is  then  closed,  an  image  of  the  object 
remains  for  a  short  time,  diminishing  in  brightness  at  first  rapidly,  then 
more  slowly.  This  is  a  positive  after-image,  and  by  careful  observa- 
tion it  may,  under  certain  conditions,  be  seen  that  the  positive  after- 
image of  a  white  object,  of  a  slit  illuminated  by  sunlight,  for  example, 
undergoes  changes  of  colour  as  it  fades,  passing  through  greenish -blue, 
indigo,  violet,  or  rose,  to  dirty  orange.  On  the  Voung-Helmholtz 
theory  this  is  explained  by  the  supposition  that  the  excitation  tlocs 
not  decline  with  the  same  rapidity  in  the  three  hypothetical  components. 
If  the  object  is  looked  at  for  a  longer  time,  or  if  the  eye  is  fatigued,  a 
dark  or  negative  image  may  be  seen  upon  the  faintly-illuminated  ground 
of  the  closed  eyes;  but  negative  after-images  may  be  more  easily 
obtained  when  the  eye,  after  being  made  to  fix  a  small  white  object  on 
a  black  ground,  is  suddenly  turned  upon  a  white  or  neutral  tint  surface. 

Here  Helmholtz  supposed  the  portion  of  the  retina  on  which  the 
image  of  the  object  is  formed  to  be  more  or  less  fatigued.  And  tliis 
fatigue  will  extend  to  all  three  kinds  of  fibres;  so  that  white  light  of  a 
given  intensity  will  now  cause  less  excitation  in  this  part  than  in  tlie 
rest  of  the  retina.  It  is  easy  to  understand  that  the  negative  after- 
image of  a  coloured  object  will  be  seen,  upon  a  white  ground,  in  the 


IOI6  THE  SENSES 

complementary  colour,  for  the  components  chiefly  excited  by  the  latter 
will  have  been  least  fatigued.  The  negative  after-images  seen  when 
the  eye,  after  receiving  the  positive  impression,  is  turned  upon  a  coloured 
ground,  vary  wath  the  colour  of  the  object  and  ground  in  a  manner  which 
has  been  explained  as  due  to  fatigue  of  one  or  other  component.  It 
is  difficult,  however,  to  reconcile  the  fatigue  hypothesis  of  the  after- 
image with  all  the  facts.  Hering  supposes  that  the  retina  is  not 
passively  fatigued,  but  that  a  metabolic  change  is  set  up  in  it  which  is 
of  the  opposite  kind  to  that  caused  by  the  original  excitation  (see 
p.  1017). 

The  phenomena  of  negative  after-images  are  often  included  together 
as  examples  of  successive  contrast,  the  name  implying  mutual  in- 
fluences of  the  portions  of  the  retina  (or  retino-cerebral  apparatus) 
successively  stimulated.  We  have  now  to  consider  simultaneous 
contrast,  often  spoken  of  simply  as  contrast. 

Contrast. — A  small  white  disc  in  a  black  field  appears  whiter,  and  a 
small  black  disc  in  a  white  field  darker,  than  a  large  surface  of  exactly 
the  same  objective  brightness.  A  disc  with  alternate  sectors  of  white 
and  black,  so  arranged  that  tlie  proportion  of  white  to  black  increases 
in  each  zone  from  centre  to  circumference,  when  set  in  rotation,  ought, 
by  Talbot's  law,  to  show  sharply  marked  and  uniform  rings,  of  which 
each  is  brighter  than  that  internal  to  it.  But  each  zone  appears 
brightest  at  its  inner  edge,  where  it  borders  on  a  zone  darker  than  itself, 
and  darkest  at  its  outer  edge,  where  it  borders  on  a  brighter  zone.  A 
plausible  explanation  of  this  is  based  on  the  assumption  that  in  the 
neighbourhood  of  an  excited  area  of  the  retina,  as  well  as  within  the 
area  itself,  the  excitability  is  diminished ;  and  the  same  explanation  has 
been  extended  to  the  contrast  phenomena  of  coloured  objects.  A  small 
piece  of  grey  paper,  e.g.,  is  placed  on  a  green  sheet.  The  grey  patch 
appears  in  the  complementary  colour  of  the  ground — viz.,  pink  or 
rose-red  (Meyer).  The  red  colour  is  much  stronger  if  the  whole  is 
covered  with  translucent  tracing-paper.  Here  we  may  suppose  that 
the  fatigue  of  the  substance  or  component  chiefly  affected  by  the  ground 
colour  spreads  into  the  portion  of  the  retina  occupied  by  the  image  oi 
the  grey  paper;  the  white  light  coming  from  the  latter,  therefore, 
affects  mainly  the  component  connected  with  the  sensation  of  the  com- 
plementary colour. 

The  curious  phenomenon  of  coloured  shadows  is  also  an  illustration 
of  contrast.  They  may  be  produced  in  various  ways.  For  example, 
when  a  lamp  is  lit  in  a  room  in  the  twilight,  before  it  has  yet  grown 
too  dark,  the  shadows  cast  by  opaque  objects  on  a  white  window-blind 
are  coloured  blue.  The  yellow  light  of  the  lamp  overpowers  the  feeble 
daylight  which  passes  through  the  blind,  and  the  general  ground  is 
yellowish;  but  wherever  a  shadow  is  thrown  it  appears  of  a  bluish  tint 
in  contrast  to  the  yellow  ground.  Here  the  only  illumination  the  eye 
receives  from  the  region  occupied  by  the  shadow  is  the  feeble  daylight. 
Falling  upon  an  area  in  which  the  component  chiefly  affected  by  yellow 
rays  is  more  or  less  fatigued,  it  causes  a  sensation  of  the  complementary 
colour.  As  darkness  comes  on,  the  shadows  become  black,  for  now 
practically  no  light  at  all  comes  from  them. 

Helmholtz  looked  upon  simultaneous  contrast  as  a  result  of  false 
judgment,  and  not  of  a  change  of  excitability  in  parts  of  the  retina 
bordering  on  the  actually  excited  parts,  h'or  the  sake  of  perspective, 
it  will  be  worth  while  to  apply  this  theory  by  way  of  illustrating  it,  to 
the  explanation  of  the  case  of  contrast  we  liave  just  been  considering, 
from  the  other  point  of  view,  in  Meyer's  experiment.  Helmholtz's  ex- 
planation of  this  experiment  is  as  follows:  When  a  coloured  surface  is 


VISION  1017 

covered  with  translucent  paper,  the  latter  appears  as  a  colourerl  covering 
spread  over  the  field.  'll»e  mind  does  not  recognize  that  at  the  grey 
patch  there  is  any  breach  of  continuity  in  this  covering;  it  is  therefore 
assumed  that  the  greenish  veil  extends  over  this  spot  too.  Now.  the 
grey  seen  through  tiic  translucent  white  paper  is  objectively  white — i.e., 
sends  to  the  eye  the  vibrations  which  together  would  give  the  sensation 
of  white  light.  But  with  a  green  veil  in  front  of  it,  this  could  only 
happen  if  the  really  grey  patch  was  the  colour  complementary  to  green 
— that  is,  rose-red.  The  mind,  therefore,  judges  falsely  that  the  patch 
is  red.  Hering  has  severely  criticized  this  theory  of  Hclmholtz  as  to 
false  judgments;  and  the  weight  of  evidence  ccfiainly  seems  to  be  in 
favour  of  the  view  that  simultaneous,  like  successive,  contrast  is  due 
to  the  influence  of  one  portion  of  the  retina,  or  retino-cerebral  apparatus, 
on  another. 

Hering 's  Theory  of  Colour  Vision. — The  Young- Hehnholtz  theory 
of  colour  visit)!!  has  not  met  with  universal  acceptance.  The  best- 
known  rival  theory  is  that  of  Hering,  who  takes  his  stand  upon  the 
fact  that  certain  visual  sensations  (red,  yellow,  green,  blue,  white, 
black)  do  appear  to  us  to  be  fundamentally  distinct  from  each  other 
while  all  the  rest  are  obviously  mixtures  of  these.  Accepting  these 
six  as  primary  sensations,  he  assumes  the  existence  in  the  visual 
nervous  apparatus  of  substances  of  three  different  kinds,  which  may 
be  called  the  black-white,  the  green-red,  and  the  blue-yellow.  Like 
all  other  constituents  of  the  body,  these  substances  are  broken  down 
and  built  up  again — in  other  words,  undergo  disassimilation  and 
assimilation,  destructive  and  constructive  metabolism.  The  sensa- 
tions of  black,  of  green,  and  of  blue  he  supposes  to  be  associated  with 
the  constructive,  and  the  sensations  of  white,  of  red,  and  of  yellow 
with  the  destructive,  processes  in  the  three  substances.  The  black- 
white  substance  is  used  up  under  the  influence  of  all  the  rays  of  the 
spectrum,  but  in  different  degrees;  the  smaller  the  quantity  of  light 
falling  on  the  retina,  the  more  rapidly  is  it  restored,  and  the  more 
intense  is  the  sensation  of  black.  The  green-red  substance  is  built 
up  by  green  rays,  broken  down  by  red.  The  blue-yellow  substance 
is  destroyed  by  yellow  rays,  restored  by  blue.  A  prominent  dif- 
ference between  this  and  the  Young-Helmholtz  theory,  and,  so  far 
as  it  goes,  an  advantage,  is  that  Hering's  theory  attempts  to  assign 
a  direct  objective  cause  for  the  visual  sensations  of  white,  black, 
and  yellow,  as  well  as  for  red,  green,  and  blue,  instead  of  making 
the  sensations  depend  upon  the  magnitude  of  the  stimulation  pro- 
cess. When  any  of  the  visual  substances  are  consumed  at  one  part 
of  the  retina,  they  are  supposed  to  be  more  rapidly  built  up  in  the 
surrounding  parts,  and  in  this  way  many  of  the  phenomena  of 
simultaneous  contrast  receive  an  easy  and  natural  explanation.  The 
same  is  true  of  the  simpler  phenomena  of  after-images  or  successive 
contrast.  But  in  applying  the  theory  to  the  more  complicated 
phenomena  difficulties  soon  emerge,  which,  to  say  the  least,  are  not 
less  formidable  than  those  connected  with  the  Young-Helmholtz 


ioi8 


THE  SENSES 


theory.  Neither  theory,  in  short,  can  be  considered  more  than  a 
partially  successful  attempt  to  grapple  with  a  very  complex  mass  of 
facts.  Each,  however,  has  been  fruitful  in  leading  to  the  discovery 
of  new  facts — a  great  merit  in  a  scientific  hypothesis. 

Sensibility  of  Different  Parts  of  the  Retina — ^Perimetry. — The 
perception  of  colours,  like  the  perception  of  white  light,  is  not 
equally  distinct  over  the  whole  retina.  We  have  repeatedly  had 
occasion  to  refer  to  the  fovea  centralis  as  the  region  of  most  distinct 
vision;  but  it  would  be  a  mistake  to  suppose  that  it  is  therefore 
necessarily  more  sensitive  than  the  rest  of  the  retina.  As  a  matter 
of  fact,  when  the  minimum  intensity  of  white  light  which  will  cause 
an  impression  at  all  is  determined  for  each  portion  of  the  retina,  it 

is  found  that  the  fovea 
centralis  requires  a  some- 
what stronger  stimulus 
than  the  zone  immedi- 
ately surrounding  it.  Ob- 
jects only  a  little  brighter 
than  the  general  ground 
on  which  they  lie — e.g., 
very  faint  stars — are  best 
seen  when  the  eye  is 
directed  a  little  to  one 
side.  This  has  been  attri- 
buted to  the  absence  of 
visual  purple  '  from  the 
fovea,  in  accordance  with 
the  theory  previously 
alluded  to  that  the  visual 
purple  acts  as  a  mechan- 
ism which  '  adapts  '  the 
retina  for  the  perception 
of  light  of  varying  inten- 
sity. But,  with  this  ex- 
ception, the  sensibility  of 
the  retina  diminishes  steadily  from  centre  to  periphery,  both  for 
white  and  for  coloured  light. 

When  the  eye  is  fixed,  and  the  visual  field — that  is,  the  whole 
space  from  which  light  can  reach  the  retina  in  the  given  position,  or, 
what  comes  to  the  same  thing,  the  projection  of  the  visual  field  on 
the  retina  by  straight  lines  passing  through  the  nodal  point — 
explored  by  means  of  a  perimeter  (Figs.  430,  431),  it  is  found  that, 
under  ordinary  conditions,  a  white  object  is  seen  over  a  wider  field 
than  any  coloured  object,  a  blue  object  over  a  wider  field  than  a 
red,  and  a  red  over  a  wider  field  than  a  green  object.  The  exact 
shape,  as  well  as  size,  of  the  visual  field  also  differs  somewhat  for 


Fig.  430  — PriCbtlfV  Smith's  Perimeter  K',  rest 
for  rhm;  O,  position  of  eye,  Ob  object,  white  or 
coloured,  which  slides  on  the  graduated  arc  B ; 
/,  point  fixed  by  the  eye. 


VISION 


lOIQ 


different  colours.  In  disease  of  the  retina,  or  of  the  visual  path 
between  it  and  the  cortex,  or  of  the  visual  cortex  itself,  the  abridg- 
ment of  the  field  for  white  and  for  monochromatic  light  as  mapped 
out  by  obserrations  with  the  perimeter  is  often  of  value  in  diagnosis. 
Although  it  has  been  shown  by  Aubert  and  others  that  monochro- 
matic light  of  considerablf.  intensity  can  be  pt-rccivt-d  over  tin-  whole 
retina,  yet  it  may  be  said  that  the  retinal  rim  is  even  then  relatively 
and,  under  ordinary  conditions,  absolutely  colour-blind.     This  and 


xn 


Fig.  431- — Perimetric  Chart  of  Right  Eye  (after  Hirschberg).  The  numbers  repre- 
sent degrees  of  the  visual  field  measured  on  the  graduated  arc  of  the  perimeter. 
tv,  boundary  of  field  for  white  object ;  b,  for  blue ;  r.  for  red ;  g,  for  green ;  m.  blind 
spot ;  M,  medial,  and  L.  lateral  side  of  the  field  of  vision.  The  Roman  numbers 
represent  twelve  meridians  of  the  retina,  each  making  an  angle  of  30"  with 
the  next.  They  fix  the  '  longitude  '  of  any  point  in  the  field.  The  concentric 
circles  indicated  by  Arabic  numbers  represent  angular  distances  frum  the 
fixation  point  in  the  planes  of  these  meridians.  They  give  the  '  latitude  '  of  any 
point. 

other  facts  have  given  rise  to  thetheory  (p.  1007)  that  the  rods,  which 
are  alone  present  at  the  ora  serrata,  are  concerned  in  achromatic 
vision  (under  conditions  of  dark  adaptation),  the  cones  in  colour 
vision  as  well  as  in  achromatic  vision  (under  daylight  conditions). 

This  brings  us  to  the  subject  of  colour-blindness,  a  phenomenon 
of  great  interest  in  its  theoretical  as  well  as  in  its  practical  bearings. 

Colour-Blindness. — A  consicKrable  number  of  persons  (about 
4  per  cent,  of  all  males,  but  only  one-tenth  of  this  proportion  of 


IO20  THE  SENSES 

females)  are  deficient  in  the  power  of  distinguishing  between  certain 
colours.  They  are  said  to  be  colour-bhnd ;  but  the  term  must  not 
be  taken  to  signify  that  they  are  absolutely  devoid  of  colour-sensa- 
tions. A  very  small  minority  of  the  colour-blind  appear  to  have 
but  one  sensation  of  colour  tone,  everjrthing  appearing  as  white, 
grey,  or  black  (total  colour-blindness,  sometimes  called  mono- 
chromatic vision).  All  colours  are  confused  by  them,  but  differences 
of  brightness  are  correctly  appreciated.  Probably  the  totally 
colour-blind  person  receives  somewhat  the  same  impressions  from 
a  coloured  picture  as  the  normal  person  does  from  a  reproduction 
of  the  same  picture  in  black-and-white.  There  are  close  resemblances 
between  the  vision  of  the  totally  colour-bhnd  eye  and  that  of  the 
normal  eye  adapted  by  resting  in  the  dark  for  twihght  vision.  The 
fovea  is  relatively,  and  in  some  cases  absolutely,  insensitive  to 
Hght,  while  the  peripheral  portion  of  the  retina  is  normal,  or  nearly 
normal,  in  this  regard.  This  is  the  foundation  of  the  theory  that  in 
total  colour-blindness  the  cones  are  devoid  of  their  normal  func- 
tions, and  that  the  hypothetical  mechanism  for  twilight  vision  (the 
rods)  is  functioning  alone.  In  another  condition  (night-blindness, 
or  hemeralopia)  it  is  sometimes  assumed  that  the  other  mechanism 
(that  of  the  cones)  which  is  adapted  for  daylight  vision,  and  has 
little  power  of  dark-adaptation,  is  alone  acting.  But  it  cannot  be 
said  that  this  has  been  proved. 

The  rest  of  the  colour-blind  are  dichromatic — i.e.,  their  colour 
reactions  seem  to  correspond  only  to  two  of  the  fundamental  colour 
sensations  of  the  normal  person  and  their  combinations,  in  addition 
to  white.  Of  the  dichromates  a  very  few  confuse  blue  with  yellow. 
The  great  majority  are  unable  to  distinguish  between  red  and  green. 
The  condition  will  be  most  easily  understood  by  considering  some 
of  the  extraordinary  mistakes  which  may  be  made  by  the  colour- 
blind, without  necessarily  leading  them  to  suspect  that  there  is  any- 
thing abnormal  in  their  vision.  Thus,  to  quote  the  words  of  a 
distinguished  writer  on  this  subject,  himself  a  sufferer  from  the 
deficiency:  '  A  naval  officer  purchases  red  breeches  to  match  his 
blue  uniform ;  a  tailor  repairs  a  black  article  of  dress  with  crimson 
cloth;  a  painter  colours  trees  red,  the  sky  pink,  and  human  cheeks 
blue.'  The  shoemaker,  Harris,  the  discoverer  of  colour-bhndness, 
picked  up  a  stocking,  and  was  surprised  to  hear  other  people 
describe  it  as  a  red  stocking;  it  seemed  to  him  only  a  stocking. 
The  celebrated  Dalton  was  twenty-six  years  of  age  before  he  knew 
that  he  was  colour-blind.  He  matched  samples  of  red,  pink, 
orange,  and  brown  silk  with  green  of  different  shades;  blue  both 
with  pink  and  with  violet ;  lilac  with  grey. 

When  the  condition  of  vision  in  dichromates  is  tested  by  means  of 
the  spectrum,  it  is  found  that  they  fall  into  two  classes:  (i)  A  class 
^of  green-blind)  by  whom  the  whole  of  the  sjjectrum  from  red  to  yellow  is 
d  >scribedasyellowof  different  degreesof  brightness  (intensity) ;  the  green 


VISION  1 021 

appears  as  a  pale  yellow  with  a  grey  or  white  band  in  its  midst;  while 
the  violet  end  is  seen  as  different  snades  of  blue.  (2)  A  class  of  (red- 
blind)  whose  whole  spectrum,  from  red  to  green,  is  seen  as  green  of 
different  intensities,  the  extreme  red  being  entirely  invisible.  The 
violet  end  is  blue,  as  in  (i),  and  there  is  a  band  of  white  or  grey  near 
the  blue  end  of  the  green. 

Sir  John  Herschell  explained  Dalton's  peculiarity  of  vision  on  the 
hypothesis  that  he  only  possessed  two,  instead  of  three,  primary 
sensations. 

On  the  Young-Helmholtz  theory,  the  missing  sensation  is  supposed 
to  be  either  red  or  green.  At  the  intersection  of  the  curves  that  repre- 
sent the  violet  and  green  sensations  (Fig.  428),  the  red-blind  individual 
will  see  what  he  describes  as  white — viz.,  the  sensation  prcKluced  by 
the  stimulation  of  the  only  two  components  he  possesses.  Similarly, 
at  the  intersection  of  the  red  and  violet  curves  the  green-blind  person 
will  see  what  is  white  to  him. 

Those  who  have  attempted  to  explain  colour-blindness  on  Hering's 
theory  have  usually  assumed  that  the  colour-blind  possess  the  blue- 
yellow,  but  lack  the  green-red  visual  substance.  So  that  on  this  theory 
there  should  be  no  difference  between  red-blindness  and  green-blind- 
ness. But  V.  Kries,  in  a  study  of  twenty  cases  of  congenital  partial 
colour-blindness,  brings  forward  strong  evidence  that  the  red-green 
blind  can  be  divided,  as  regards  the  comparison  of  red  (lithium)  and 
orange  (sodium)  light,  into  two  sharply-separated  groups — a  result 
which  is,  so  far  as  it  goes,  in  favour  of  the  Young-Helmholtz  theory 
and  against  the  theory  of  Hering. 

The  observations  of  Burch  on  temporary  colour-blindness  produced 
by  placing  the  eye  behind  a  transparent  coloured  screen  and  focussing 
a  beam  of  strong  sunlight  on  it,  lend  additional  support  to  the  former 
theory.  Thus,  if  a  spectrum  is  looked  at  after  green-blindness  has  been 
induced  by  exposure  of  the  eye  to  green  light,  the  red  p>ortion  of  the 
spectrum  seems  to  pass  into  the  blue,  and  no  intermediate  green  band 
is  seen.  If  tlie  eye  is  exposed  to  yellow  light  it  becomes  temporarily 
blind  not  only  for  yellow,  but  also  for  red  and  green.  This  is  in  favour 
of  the  assumption  of  the  Young-Helmholtz  theory  that  the  sensation 
of  yellow  is  caused  when  the  retinal  elements  concerned  in  the  production 
of  the  sensations  of  red  and  green  are  simultaneously  stimulated.  It  is, 
however,  equally  difficult  to  reconcile  some  of  the  phenomena  of  colour- 
blindness with  the  Young-Helmholtz  theory.  Anomalies  and  defects 
of  colour-sensation  are  common  accompaniments  of  pathological  lesions 
of  the  visual  apparatus,  and  can  be  pro(hiccd  by  various  drugs,  as  by 
abuse  of  tobacco.  But  colour-blindness,  in  its  true  sense,  is  con- 
genital, often  hereditary;  the  colour-blind  are  '  bom,  not  made.'  And 
although  the  condition  cannot  be  cured,  it  is  of  great  importance  that 
it  should  be  recognized  in  the  case  of  persons  occupying  positions  such 
as  those  of  engine-drivers,  railway-guards,  and  sailors,  in  which  coloured 
lights  have  to  be  distinguished.  For,  while  it  is  true  that  the  sensations 
which  red  and  green  lights  give  the  colour-blind  are  far  from  being 
identical  (Pole)  under  favourable  conditions,  it  is  precisely  when  the 
conditions  are  unfavourable— as  in  a  fog  or  a  snow-storm — that  the 
capacity  of  distinguishing  them  becomes  invaluable  (Practical  Ex- 
ercises, p.  1069). 

Tt  radiation.  —  The  phenomenon  known  as  irradiation  was  first 
described  by  Kepler,  who  gave  as  an  example  the  appearance  known 
as  the  '  new  moon  in  the  old  moon's  arms,'  where  the  crescent  of  the 
new  moon  seems  to  overlap  and  embrace  the  unilluminated  portion  of  the 
lunar  disc.     A  white  circle  on  a  black  ground  (Fig.  432)  appears,  in 


I022  THE  SENSES 

a  good  light,  to  be  larger  than  an  exactly  equal  black  circle  on  a  white 
ground.  The  explanation  is  as  follows:  Owing  to  the  aberration  of  the 
refractive  media  of  the  eye  (p.  987),  all  the  rays  proceeding  from  the 
luminous  object  are  not  brought  accurately  to  a  focus  on  the  retina, 
and  the  image  is  surrounded  by  diffusion  circles  (p.  988)  which  encroach 
upon  the  unilluminated  boundary.  Physically  these  represent  a 
weaker  illumination  than  that  of  the  image  proper,  and  therefore  the 
latter  ought  to  stand  out  in  its  real  size  as  a  brighter  area  surrounded  by 
weaker  haloes.  That  this  is  not  the  case,  and  that  the  image  is  pro- 
jected in  its  full  brightness  for  a  certain  distance  over  its  dark  boundary, 
is  due  to  the  fact  that  the  eye  does  not  recognize  very  small  differences 
of  brightness.  When  the  accommodation  is  not  perfect,  the  diffusion 
circles  are,  of  course,  much  wider,  and  irradiation  is  better  marked  when 
the  object  is  a  little  out  of  focus. 

The  Movements  of  the  Eyes. — That  the  eyes  may  be  efficient 
instruments  of  vision,  it  is  necessary  that  they  should  have  the 
power  of  moving  independently  of  the  head.  An  eye  which  could 
not  move,  though  certainly  better  than  an  eye  which  could  not  see, 

would  yet  be  as  imperfect  after 
its  kind  £is  a  ship  which  could 
/  —         \       run  before  the  wind,  but  could 

not  tack.  The  mere  fact  that 
the  angle  between  the  visual 
axes  must  be  adapted  to  the 
distance  of  the  object  looked  at 
Pj^  renders   this   obvious;  and  the 

beauty  of  the  intrinsic  mechan- 
ism of  the  eyeball  has  its  fitting  complement  in  the  precision, 
delicacy,  and  range  of  movement  conferred  upon  it  by  its  extrinsic 
muscles. 

Not  only  are  movements  of  convergence  and  divergence  of  the 
eyeballs  necessary  in  accommodating  for  objects  at  different  dis- 
tances, but  without  compensatory  movements  of  the  eyes  it  would 
be  impossible  to  avoid  diplopia  with  every  movement  of  the  head; 
for  the  images  of  an  object  fixed  in  one  position  of  the  head  would 
not  continue  to  fall  on  corresponding  points  of  the  retinae  in  another 
position. 

All  the  complicated  movements  of  the  eyeball  may  be  looked 
upon  as  rotations  round  axes  passing  through  a  single  point,  which 
to  a  near  approximation  always  remains  fixed,  and  is  situated  about 
177  mm.  behind  the  centre  of  the  eye. 

The  position  which  the  eyeballs  take  up  when  the  gaze  is  directed  to 
the  horizon,  or  to  any  distant  point  at  the  level  of  the  eyes,  is  called 
the  primary  position.  Here  the  visual  axes  are  parallel,  and  the  plane 
passing  through  them  horizontal.  While  the  head  remains  fixed  in  this 
position,  the  eyeballs  can  rotate  up  or  down  around  a  horizontal  axis, 
or  from  side  to  side  around  a  vertical  axis;  or  upwards  and  inwards, 
downwards  and  o'.twards,  downwards  and  inwards,  and  upwards  and 
outwards  around  oblique  axes,  which  always  lie  in  the  same  plane  as 
the  vertical  and  horizontal  axes  of  rotation — i.e.,  in  the  vertical  plane 


VISION 


1023 


These  are  the  internal  and 

/hi   iUD 


passing  through  the  fixed  centre  of  rotation.  These  facts,  spoken  of 
collectively  as  Listing's  law,  and  first  deduced  by  liim  from  theoretical 
considerations,  were  afterwards  proved  experimentally  by  llelmholtz 
and  Donders.  It  necessarily  follows  from  Listing's  law  (and  this  is, 
indeed,  another  way  of  stating  it)  tliat  in  moving  from  the  primary  posi- 
tion into  any  other,  there  is  no  rotation  of  the  eyeball  round  the  visual 
axis — no  wheel-movement,  as  it  is  called. 

A  true  rotation  of  the  eye  round  the  visual  axis  (UK's,  however,  occur 
when  the  eyes  are  converged  as  in  accommodation  for  a  near  object, 
each  eyeball  rotating  towards  the  temporal  side.  This  is  especially  the 
case  when  the  eyes  are  at  the  same  time  converged  and  directed  down- 
wards; and  the  rotation  may  amount  to  as  much  as  5°.  When  the 
head  is  rolled  from  side  to  side,  while  the  eyes  are  kept  fixed  on  an 
object,  a  slight  compensatory  rotation  of  the  eyeballs  takes  place 
against  the  direction  of  rotation  of  tlie  head.  Tlie  amount  of  rotation 
of  the  eyes  is  relatively  greater  for  small  than  for  large  movements  of 
the  head  (eye  3°  for  head  20°;  eye  10°  for  head  80° — Kiister). 

The  Extrinsic  Muscles  of  the  Eyes. — The  eyeball  is  acted  upon  by 
six  muscles  arranged  in   three  pairs,   which   may  be  considered, 
roughly  speaking,  as  antagonistic  sets, 
external  recti,  the   superior  and 
inferior   recti,    and   the   superior 
and  inferior  obliqui. 

Although  the  movements  of  the 
eye  have  been  very  fully  studied, 
and  are,  upon  the  whole,  well 
understood,  our  knowledge  of  the 
manner  in  which  any  given  move- 
ment is  brought  about,  and  of  the 
exact  action  of  the  muscles  which 
take  part  in  it,  is  by  no  means 
as  copious  and  precise.  From 
the  nature  of  the  case,  the  greater 
part  of  what  we  do  know  has 
been  inferred  from  the  anatomical 
relations  of  the  muscles  as  re- 
vealed by  dissection  in  the  dead 
body  rather  than  gained  from  actual  observation  of  the  hving  eye. 
A  plane,  called  I  ho  plane  of  traclinn,  is  supposed  to  pass  through  the 
middle  points  of  the  origin  and  inst-rlion  of  the  muscle  whose  action 
is  to  be  investigated,  and  through  the  centre  of  rotation  of  the 
eyeball.  A  straight  line  drawn  at  right  angles  to  this  platn-  through 
the  centre  of  rotation  is  evidently  the  axis  roimd  which  the  muscl:' 
when  it  contracts  will  cause  the  eye  to  rotate,  provided  that  th.'. 
fibres  of  the  muscle  are  synunelrically  distributed  on  each  sitle  of 
the  plane  of  traction.  The  axes  of  rotation  of  the  antagonistic 
pairs  almost,  but  not  completely,  coincide  with  each  other.  The 
common  axis  of  the  external  and  internal  recti  practically  coincides 
with  tho  vertical  axis  of  the  eyeball  (l-'ig.  433)  in  tho  primary  posi- 


Rtni 


n  ext         H  to/ 

Fig.  433. — Horizontal  Section  of  Left 
Eye.  Arrows  show  direction  of 
pull  ef  the  muscles.  The  axis  of 
rotation  of  the  external  and  internal 
recti  would  pass  tlirounh  the  inter- 
section of  a  and  ji  at  ri|L;ht  angles 
to  the  plane  of  the  paper. 


I024  T^HE  SENSES 

tion.  The  eye  is  turned  towards  the  temple  when  the  external 
rectus  alone  contracts,  towards  the  nose  when  the  internal  rectus 
alone  contracts.  The  common  axis  of  the  superior  and  inferior 
recti,  /5,  lies  in  the  horizontal  visual  plane  in  the  primary  position, 
but  makes  an  angle  of  about  20°  with  the  transverse  axis,  its  inner 
end  being  tilted  forwards.  The  consequence  is  that  contraction 
of  the  superior  rectus  turns  the  eye  up,  and  contraction  of  the 
inferior  rectus  turns  it  down,  but  both  movements  are  also  com- 
bined with  a  slight  inward  rotation.  The  common  axis  of  the 
oblique  muscles,  «,  makes  an  angle  of  60°  with  the  transverse  axis, 
the  outer  end  of  it  being  the  most  anterior.  The  direction  of  traction 
of  the  superior  oblique  is,  of  course,  given  not  by  the  line  joining 
its  bony  origin  and  its  insertion,  but  by  the  direction  of  the  portion 
reflected  over  the  pulley.  When  the  superior  oblique  contracts 
alone,  the  eyeball  is  rotated  outwards  and  downwards;  the  inferior 
oblique  causes  an  outward  and  upward  rotation.  None  of  the 
common  axes  of  rotation  of  the  pairs  of  muscles,  except  that  of  the 
external  and  internal  recti,  lies  in  Listing's  plane.  Now,  as  we  have 
seen  that  every  movement  which  the  eye,  supposed  to  be  originally 
in  the  primary  position,  can  execute  may  be  considered  as  a  rota- 
tion round  an  axis  in  this  plane,  it  is  clear  that  every  movement, 
except  truly  transverse  rotation,  must  be  brought  about  by  more 
than  one  pair  of  muscles.  For  vertical  rotation,  the  inward  pull  of 
the  superior  rectus  is  antagonized  by  a  simultaneous  outward  pull 
of  the  inferior  oblique;  for  downward  rotation,  the  inferior  rectus 
and  superior  oblique  act  together.  In  oblique  movements,  a  muscle 
of  each  of  the  three  pairs  is  concerned.  The  effect  on  the  eyeball 
of  simultaneous  contraction  of  certain  pairs  of  muscles  may  be 
summarized  thus: 

External  rectus  (outward) -i- internal  rectus  (inward)  =  none. 

Superior  rectus  (upward  and  inward) -f  inferior  oblique  (upward  and 
outward)  =  upward. 

Inferior  rectus  (downward  and  inward) -h  superior  oblique  (downward 
and  outward)  =  downward. 

Section  II. — Hearing. 

The  transverse  vibrations  of  the  ether  fall  upon  all  parts  of  the  surface 
of  the  body,  but  only  find  nerve-endings  capable  of  giving  the  sensa- 
tion of  light  in  the  little  discs,  which  we  call  the  retinae.  So  the  much 
longer  and  slower  longitudinal  waves  of  condensation  and  rarefaction 
which  are  being  constantly  originated  in  the  air  or  imparted  to  it  by 
solid  or  liquid  bodies  that  have  been  themselves  set  vibrating  fall  upcn 
all  parts  of  the  surface,  but  only  produce  the  sensation  of  sound  when 
they  strike  upon  the  tiny  mechanism  of  the  internal  ear. 

But  just  as  the  ethereal  vibrations,  and  especially  those  of  greater 
wave-length,  are  able  to  excite  certain  end-organs  in  the  skin  which 
have  to  do  with  the  sensation  rf  lemperature,  so  the  soimd-waves, 
when  sufficiently  large,  are  also  capable  of  stimulating  certain  cutaneous 


HEA  RING 


1025 


nerves  and  of  giving  rise  to  a  sensation  of  intermittent  pressure  or  thrill. 
This  is  readily  perceived  when  the  finger  is  immersed  in  a  vessel  of 
water  into  which  dips  a  tube  connected  with  a  source  of  sound,  or  when 
a  vibrating  bell  or  tuning-fork  is  touched.  So  far  as  we  know,  what 
takes  place  in  the  ear  is  essentially  similar— that  is  to  say,  a  mechanical 
stimulation  of  the  ends  of  the  auditory  nerve,  but  a  stimulation  which 
acts  through,  and  is  graduated  and  controlled  by,  a  special  intermediate 
mechanism. 

As  the  visual  apparatus  consists  of  a  sensitive  surface,  the  retina, 
which  contains  the  end-organs  of  the  optic  nerve  and  of  dioptric 
arrangements  which  receive  and  focus  the  rays  of  Hght,  the  auditory 
apparatus  consists  of  the  sensitive  end-organs  of  the  cochlear  divi- 
sion of  the  eighth  nerve  and  of  a  mechanism  which  receives  the 
sound-waves  and  communicates  them  to  these. 

Physiolos;ical  Anatomy  of  the  Ear.— At  the  bottom  of  the  external 
auditory  meatus  lies  the  membrana  tympani,  a  nearly  circular  mem- 
brane set  like  a  drum-skin  in  a 
ring  of  bone,  and  separating  the 
meatus  from  the  tympanum  or 
middle  ear.  Its  external  surface 
looks  obliquely  downwards,  and 
at  the  same  time  somewhat  for- 
wards, so  that  if  prolonged  the 
membranes  of  the  two  ears  would 
cut  each  other  in  front  of,  and  also 
below,  the  horizontal  line  passing 
through  the  centre  of  each  (Figs. 

434.  435)- 

The  tympanum  contains  a 
chain  of  little  bones  stretching 
right  across  it  from  outer  to  inner 
wall.  Of  these  the  malleus,  or 
hammer,  is  the  most  external. 
Its  manubrium,  or  handle,  is  in- 
serted into  the  membrana  tym- 
pani, which  is  not  stretched  taut 
within  its  bony  ring,  but  bulges 
inwards  at  the  centre,  where  the 
handle  of  the  malleus  is  attached. 
The  stapes,  or  stirrup,  is  the  most 
internal  of  the  chain  of  ossicles, 
and  is  inserted  by  its  foot-plate 
into  a  small  oval  opening — the 
foramen  ovale — on  the  inner  wall  of  the  tympanic  cavity.  A  mem- 
branous ring — tlie  orbicular  membrane — surrounds  the  foot  of  the 
stapes,  helping  to  fill  up  the  foramen  and  attaching  the  bone  to  its 
edges.  The  inner  surface  of  the  foot  of  the  stapes  is  in  contact  with 
tlie  perilymph  of  the  internal  ear.  The  incus,  or  anvil,  forms  a  link 
between  tlie  malleus  and  the  stapes.  The  auditory  ossicles,  as  well  as 
the  whole  cavity  of  the  tympanum,  are  covered  by  pavement  epithelium. 

The  tympanum  is  not  an  absolutely  closed  chamber;  it  has  one 
channel  of  communication  with  the  external  air — the  Eustachian  tube 
— which  opens  into  the  pharynx.  By  the  action  of  tlie  cilia  lining  this 
tube  the  scanty  secretion  of  the  middle  ear  is  moved  towards  its 
pharyngeal  opening,  which,  usually  closed,  is  opened  when  a  swallowing 

65 


Fig.  434. — The  Ear.  m,  external  meatus; 
/,  head  of  malleus;  o,  short  process  of 
malleus;  g,  handle  of  malleus;  h,  incus; 
i,  foot  of  stapes  in  oval  foramen;  e,  tym- 
panic membrane. 


I026 


THE  SENSES 


movement  occurs.  Its  function  is  to  keep  the  pressure  in  the  middle 
ear  approximately  that  of  the  atmosphere.  In  a  balloon  ascent  an 
excess  of  pressure  is  established  on  the  internal  surface  of  the  tympanic 
membrane.  In  the  air-lock  of  a  caisson  when  the  air  is  being  com- 
pressed the  excess  of  pressure  is  on  the  external  surface  of  the  membrane. 
The  feeling  of  uncomfortable  tension  is  relieved  in  both  cases  by  swallow- 
ing movements  which  allow  the  pressure  in  the  tympanum  to  adjust 
itself  to  that  in  the  pharynx.  In  catarrh  of  the  naso-pharynx  the 
orifice  may  be  occluded,  and  this  is  accompanied  by  impairment  of 
hearing  and  a  disagreeable  sensation  of  tension  in  the  ear,  owing  to 
absorption  and  consequent  rarefaction  of  the  air  in  the  tympanum. 

The    patient    ins  tine - 

-_    tively    makes    efforts 

which  increase  the  pha- 
ryngeal pressure  from 
time  to  time  so  as  to 
open  the  tube. 

The  loosely  -  jointed 
chain  of  ossicles  is 
steadied  and  its  move- 
ments directed  by  liga- 
ments and  by  the  ten- 
sion of  its  terminal  mem- 
branes. It  forms  a  kind 
of  bent  lever  by  which 
the  oscillations  of  the 
membrana  tympani  are 
transferred  to  the  mem- 
brane covering  the  ©val 
foramen,  and  at  the 
same  time  reduced  in 
size.  Two  slender 
muscles,  the  tensor  tym- 
pani and  stapedius,  con- 
tained in  the  tympanic 
cavity,  are  also  con- 
nected with  and  may 
act  upon  the  ossicles. 
The  former  lies  in  a 
groove  above  the  Eusta- 
chian tube,  and  its 
tendon,  passing  round  a 
kind  of  osseous  pulley 
(processus  cochleari- 
formis),  is  inserted  into  the  handle  of  the  malleus;  the  stapedius  is 
lodged  in  a  hollow  of  the  inner  bony  wall  of  the  tympanum.  Its 
tendon  is  attached  to  the  neck  of  the  stapes  near  its  articulation  with 
the  incus.  This  inner  wall  is  pierced  not  only  by  the  oval  foramen, 
but  also  by  a  round  opening,  the  fenestra  rotunda,  which  is  closed  by 
a  membrane  to  which  the  name  of  secondary  membrana  tympani  is 
sometimes  given. 

The  internal  ear  consists  of  the  bony  labyrinth,  a  series  of  curiously 
excavated  and  communicating  spaces  in  the  substance  of  the  petrous 
portion  of  the  temporal  bone,  filled  with  a  liquid  called  the  perilymph, 
in  whicli,  anchored  by  strands  of  connective  tissue,  floats  a  correspond- 
ing series  of  membranous  canals  (the  membranous  labyrinth),  filled 
with  a  liquid  called  endolymph.     The  labyrinth  of  the  internal  ear  is 


Fig.  435. — Tympanum  of  Left  Ear,  showing  the 
Ossicles  (Morris),  i,  superior,  and  4,  external, 
ligament  of  malleus;  2,  head;  7,  short  process,  and 
10,  manubrium  or  handle,  of  malleus;  5,  long  process 
of  incus,  terminating  in  9,  the  os  orbiculare;  6,  base, 
and  8,  head,  of  stapes;  11,  Eustachian  tube;  12,  ex- 
ternal auditory  meatus;  13,  membrana  tympani; 
3,  upper,  and  14,  lower,  part  of  tympanum. 


HEARING 


1027 


divided  into  three  well-marked  parts:  the  cochlea,  the  vestibule,  and 
the  semicircular  canals  (Fig.  436).  The  cochlea,  the  most  anterior  o£ 
the  three,  consists  of  a  con\oiuled  tube  which  coils  round  a  central 
pillar,  the  columella  or  modiolus,  like  a  spiral  staircase.  The  lamina 
spiralis  projects  from  the  modiolus  and  divides  the  tube  into  an  up|XT 
compartment,  tlie  scala  vestibuli,  and  a  lower,  the  scala  tympani 
(Fig.  437).  J  he  [lart  of  the  lamina  next  the  modiolus  is  of  bone,  but  it 
is  comjileted  at  its  outer  edge  by  a  membiane,  the  lamina  spiralis  mem- 
branacea,  or  basilar  niembranc.  I  lie  scala  tympani  abuts  on  the 
fenestra  rotunda,  and  its  perilymph  is  only  separated  from  tiie  air  of 
the  tympanic  cavity  by  the  membrane  which  clo.ses  that  opening. 
At  the  apex  of  the  cochlea  tlic  lamina  spiralis  is  incomplete,  ending  in 
a  crescentic  boi-der,  so  that  the  scala  tymi:)ani  and  the  scala  vestibuli 
here  communicate  by  a  small  opening,  the  helicotrema.  The  scala 
vestibuli  communicates  with  the  vestibule,  and  the  vestibule  with  the 
semicircular  canals,  so  that  the  perilymph  of  the  entire  labyrinth  forms 
a  continuous  sheet  separated  from  the  cavity  of  the  middle  ear  by  the 


— y 


Fig.  436. — Diagram  of  Right  Membranous  Labyrinth  (after  lestut).  i.  utricle; 
2,  3,  4.  superior,  posterior,  and  horizontal  semicircular  canals;  5,  saccule; 
6,  ductus  endolymphaticus  arising  by  two  branches,  7,  7';  8,  saecus  endo- 
lyniphaticus;  9,  canalis  cochlearis  (canal  of  the  cochlea)  ending  at  9',  and  9'; 
10,  canalis  reuniens. 


structures  that  fill  up  the  round  and  oval  foramina.  In  the  mem- 
branous labyrinth,  and  in  it  alone,  are  contained  the  end-organs  of  the 
auditory  nerve.  The  membranous  jwrtion  of  the  cochlea  is  a  small 
canal  of  triangular  section,  cut  off  from  the  scala  vestibuli  by  the  mem- 
brane of  Reissner,  whicli  stretches  from  near  the  edge  of  the  bony 
spiral  lamina  to  the  outer  wall  (h'ig.  43>i),  to  which  it  is  attachctl  by  the 
spiral  ligament.  The  canal  has  receivcil  the  name  of  the  scala  media, 
or  canal  of  the  cochlea.  The  membrane  of  Reissner  forms  its  roof. 
Its  floor  is  conijMised  (i)  of  the  projecting  edge  of  the  sjiiral  lamina, 
called  the  limbus,  and  (2)  of  the  basilar  membrane.  The  most  con- 
spicuous constituent  of  the  basilar  membrane  is  a  layer  of  stiff,  jvirallel, 
trans]xirent  fibres  arrangeil  radially  —i.r.,  in  the  direction  from  limbus 
to  spiral  ligament.  They  are  end)edded  in  a  homogeneous  material. 
Below  the  coclilear  canal  ends  blindlv,  but  communicates  by  a  side- 
channel  with  the  portion  of  the  membranous  vestibule  called  the  sac- 
cule, which  in  its  turn  communicates  with  the  utricle  l>y  the  Y-shajXid 
origin  of  the  ductus  endolymphaticus.     Into  the  utricle  open  the  three 


t028 


THE  SENSES 


semicircular  canals,  the  endolymph  of  which  has,  therefore,  free  com- 
munication with  that  of  the  vestibule  and  cochlea.  But  although  the 
semicircular  canals  and  vestibule  belong  anatomically  to  the  internal 
ear,  and  are  supplied  by  branches  of  the  auditory  nerve,  we  have  no 
positive  proof  that  in  the  higher  animals,  at  least,  they  are  in  any  way 
concerned  in  hearing;  and  since  experiment  has  assigned  them  a 
definite  function  of  another  kind  (p.  907),  we  shall  not  consider  them 


.^t™-^"T'»»»»  A^"e35i     i-v*-,. 


str.v. 


Fig.  437. — Longitudinal  Section  through  the  Cochlea  of  a  Cat  (Schafer,  after  Sobotta) 
X  25.  dc,  canal  or  duct  of  cochlea ;  scv,  scala  vestibuli ;  set,  scala  tympani ;  w,  bony 
wall  of  cochlea ;  C,  organ  of  Corti ;  mR,  Reissner's  membrane ;  n,  fibres  of  cochlear 
nerve;  gsp,  ganglion  spirale;  str.v.,  stria  vascularis. 

further  in  this  connection.  The  scala  media  contains  the  organ  of  Corti, 
which  (Fig.  439)  consists  of  a  series  of  modified  epithelial  cells  planted 
upon  the  basilar  membrane.  The  epithelial  cells  are  of  three  kinds: 
(i)  supporting  epithelial  cells;  (2)  the  pUlars  or  rods  of  Corti,  in  two 
series  (inner  and  outer),  sloped  against  each  other  like  the  rafters  of  a 
roof,  and  covering  in  a  vault  or  tunnel  which  runs  along  the  whole  of 
the  scala  media  from  the  base  to  the  apex  of  the  cochlea;  (3)  the  hair- 
cells,  around  which  the  fibres  of  the  auditory  nerve  arborize.  These 
last   are   columnar  epithelial  cells,   surmounted   by  hairs.     They  are 


HEARING 


1029 


arranged  in  several  rows,  one  row  lying  just  internal  to  tlic  inner  line 
of  pillars,  and  several  rows  external  to  tlie  outer  line  of  pillars.  Be- 
tween the  outer  hair-cells  are  supporting  cells  {cells  of  Dciters).  A  thin 
membrane,  the  reticular  lamina  or  membrana  reticularis,  composed  of 
fiddle-shaped  rings  or  phalanges,  covers  the  hair-cells,  and  tli rough 
openings  in  it  the  liairs  project.  A  tliicker  membrane,  the  membrana 
tectoria,  springing  from  the  edge  of  the  osseous  spiral  lamina  near  the 
attachment  of  Ivcissner's  membrane,  forms  a  kind  of  canopy  over  both 
pillars  and  hair-ceils.  The  outer  wall  of  the  canal  of  the  cfx:hlea  is 
clad  by  cubical  epithelium  covering  a  membrane  richly  supplied  >\'ith 
bloodvessels  {stria  vascidciyis).  'Die  fact  tliat  the  hair-cells  of  Corti's 
organ  are  connected  with  the  fibres  of  the  cochlear  division  of  the 


Fig.  438. — Vertical  Section  of  the  First  Turn  of  the  Cocliloa  (after  Rctzius).  D.C. 
canal  of  cochlea;  IC,  tuimel  of  Corti;  b.tn.  basilar  membrane;  h.i,  h.c.  internal 
and  external  hair-cells;  Mt,  membrana  tectoria;  s.sp.  spiral  groove;  str.v,  stria 
vascularis;  sp.l,  spiral  lamina;  n,  fibres  of  the  cochlear  nerve;  /,  limbiis  lamin^-o 
spiralis;  R,  Reissncr's  membrane;  s.v,  scala  vestibuli;  s.t,  scala  tympaui;  l.sp, 
spiral  ligament. 

auditory  nerve,  and  its  elaborate  structure,  suggest  that  it  must  play 
a  peculiar  part  in  auditory  sensation.  Comparative  anatomy  shows 
us  that  the  cochlea  is  the  most  highly  developed  portion  of  llie  internal 
ear,  the  last  to  api)ear  in  its  evolution,  and  the  most  specialized.  It 
is  absent  in  fishes,  which  possess  only  a  vestibule  and  one  to  three  semi- 
circular canals.  It  first  acquires  importance  in  reptiles,  but  attains 
its  highest  development  in  mammals;  and  there  is  every  reason  to 
believe  that  it  is  the  terminal  apparatus  of  the  sense  of  hearing. 

Functions  of  the  Auditory  Ossicles. — Tlio  anatomical  arrange 
nients  of  the  middle  car  suggest  tliat  the  tympanic  membrane  and 
the  chain  of  ossicles  have  the  function  of  transmitting  tlie  sound- 
waves to  the  liquids  of  the  labyrinth;  and  observation  and  experi- 


I030 


THE  SENSES 


ment  fully  confirm  this  idea.  Tracings  of  the  muvtments  of  the 
ossicles  have  been  obtained  by  attaching  very  small  levers  to  them, 
and  their  movements  have  been  directly  observed  with  the  micro- 
scope. Even  in  man  it  may  be  shown,  by  viewing  the  membrane 
through  a  series  of  slits  in  a  rapidly- revolving  disc  (stroboscope), 
that  it  vibrates  when  sound-waves  fall  on  it. 

When  the  handle  of  the  malleus  moves  inwards,  rotating  around 
an  axis  which  may  be  supposed  to  pass  through  its  neck,  its  head 
moves  in  the  opposite  direction.  The  joint  between  that  bone  and 
the  incus  is  thus  locked,  on  account  of  the  shape  of  the  articular 
surfaces.     The  long  process  of  the  incus,  constituting  the  second 


Fig.  439. — Organ  of  Corti  (Barker,  after  Retzius).  mh,  basilar  membrane;  tb,  its 
tympanal  covering;  vs,  bloodvessel  (vas  spiralc) ;  re,  meduUated  distal  processes 
of  bipolar  nerve-cells  in  the  ganglion  spirale,  passing  in  to  arborize  around  the 
hair-cells;  iS,  epithelial  cells  continuous  with  the  epithelium  of  the  sulcus 
spiralis  internus;  p,  inner  pillar  of  Corti,  with  its  basal  cell,  ft  ;  p',  outer  pillar 
with  its  basal  cell,  h' ;  i,  2,  3,  supporting  cells  of  Deiters,  whose  processes  run  up 
to  be  attached  to  the  lamina  reticularis,  r  ;  H;  Hensen's  supporting  cells;  C,  cells 
of  Claudius;  i,  internal  hair-cell  with  its  hairs,  i'  (the  upper  part  of  the  hair-cell 
is  concealed  by  the  head  of  the  inner  i)illar  of  Corti) ;  e,  external  hair-cell;  e',  hairs 
of  three  external  hair-cells;  11,  n^,  to  n*,  cross-sections  of  the  spiral  strand  of 
cochlear  nerve-fibres. 

portion  of  the  bent  lever,  passes  inwards,  carrying  with  it  the  stapes, 
which  is  attached  to  it  by  an  almost  rigid  joint,  and  the  stapes  is 
pressed  into  the  oval  foramen.  Since  the  long  process  of  the  incus 
is  about  one-third  shorter  than  the  handle  of  the  malleus,  the  ex- 
cursion of  the  point  of  the  former  is  correspondingly  smaller  than 
that  of  the  latter,  but  at  the  same  time  more  powerful.  When  the 
tympanic  membrane  passes  outwards,  the  handle  of  the  malleus 
and  foot  of  the  stapes  do  the  same.  But  the  joint  now  unlocks,  and 
excessive  outward  movement  of  the  stapes,  which  might  result  in 
its  being  torn  from  its  orbicular  attachment,  is  prevented.  The 
ossicles  vibrate  en  masse.     It  is  only  to  a  trifling  extent  that  sound 


n  LA  HI  St,  i.,l 

can  be  conducltjtl  lluoiigh  llifiii  to  the  l;ili\imili  iis  ii  mold  iiiai 
vibration;  for  when  tlicy  arc  ;uir.hyIosi'<l,  and  the  foot  of  tli">  stapes 
fixed  ininioval^ly  in  tlu;  foramen  ovale,  as  sometimes  occurs  in 
disease,  hearing  is  greatly  impaired. 

Of  course,  every  vibration  of  the  tympanic  membrane  nnist  cause 
a  corresponding  condensation  and  rart-faction  of  the  air  in  the 
middle  ear;  and  this  may  act  on  the  membrane  closing  the  fenestra 
rotunda,  and  set  up  oscillations  in  the  perilymph  of  the  scala  tym- 
pani.  ihat  this  is  a  possible  method  of  conduction  of  sound  is 
shown  by  the  fact  that,  even  after  closure  of  the  ov;d  foramen,  a 
slight  power  of  hearing  may  remain.  But  under  ordinary  con- 
ditions by  far  the  most  important  part  of  the  conduction  takes 
place  vid  the  ossicles.  And  when  it  is  remembered  that  the  tym- 
panic membrane  is  about  thirty  times  larger  than  that  which  tills 
the  oval  foramen,  it  will  be  seen  th;i,t  the  force  acting  on  unit  area 
of  the  foot  of  the  stapes  may  be  much  greater  than  that  acting  on 
unit  area  of  the  menibrana  tympani,  and  that  the  modi-  of  trans- 
mission by  the  ossicles  is  a  very  advantageous  method  of  trans- 
forming the  feeble  but  comparatively  large  excursions  of  the  tym- 
panic membrane  into  the  smaller  l^ut  more  powerful  movements  of 
the  stapes.  The  average  excursion  of  the  membrane  of  the  oval 
foramen  does  not  at  most  amount  to  inmi'  than  0()4  millimetre. 
Even  the  so-called  cranial  conduction  of  sound  when  a  tuning-fork 
is  held  between  the  teeth  or  put  in  contact  with  the  luad,  which 
was  at  one  time  supposed  to  be  due  solely  to  direct  transmission 
of  the  vibrations  through  the  bones  of  the  skull  to  the  liquids  of 
the  labyrinth  or  the  end-organs  of  the  auditory  nerve,  has  been 
shown  to  take  place,  in  great  part,  through  the  membrana  tympani 
and  ossicles;  the  vibrations  travel  through  the  bones  to  the  tym- 
panic membrane,  and  set  it  oscillating.  So  that  this  test,  when 
applied  to  distinguish  deafness  caused  by  disease  of  the  middle  ear 
from  deafness  due  to  disease  of  the  labyrinth  or  the  central  nervous 
system,  may  easily  mislead,  although  it  enables  us  to  say  whether 
the  auditory  meatus  is  blocked — by  wax,  e.g. — beyond  the  tym- 
panic meml)rane. 

A  membrane  like  a  drum-licad  has  a  note  of  its  own,  whicli  it  gives 
out  when  struck,  and  it  \ilirates  more  readily  to  this  note  than  to  any 
otlier.  It  woiiUl  cvidontly  be  a  serious  disadvantage  if  the  tympanic 
membrane,  wliosc  oliicc  it  is  to  receive  all  kinds  of  vibrations,  and 
respond  to  all,  had  a  marked  hmdamental  tone  wliich  would  l)c  con- 
tinually obtruding  it.sclf  among  otiior  notes.  TIic  difticully  is  obviated 
by  the  damping  action  of  the  ossicKs  and  the  hqiiids  of  tlie  lal>yrinth 
on  the  movements  of  the  membrane,  which  in  atUlition  is  nt)t  stretched, 
but  lies  slackly  in  its  bony  frame,  so  that  wlien  the  handle  of  tlic  malleus 
is  detached  from  it,  it  retains  its  shape  antl  position. 

The  tensor  tympani,  wlien  it  contracts,  jndls  inwards  the  handle  of 
the  malleus,  and  thus  increases  the  tension  of  the  tympanic  nu  inbrane. 
The  precise  object  of  this  is  obscure.      It  has  been  suggested  that  damp- 


I032  THE  SENSES 

ing  of  the  movements  of  the  auditory  ossicles  is  thus  secured.  Another 
theory  is  that  the  increased  tension  of  the  membrane  renders  it  more 
capable  of  responding  to  higher  tones,  and  that  the  muscle  thus  acts  as 
a  kind  of  accommodating  mechanism.  But  Hensen  has  observed  that 
the  tensor  only  contracts  at  the  beginning  of  a  sound,  and  relaxes  again 
when  the  sound  is  continued ;  and  this  is  difficult  to  reconcile  with  either 
of  these  hypotheses.  The  muscle  is  normally  excited  reflexly  through 
the  vibrations  of  the  membrana  tympani,  but  some  individuals  have 
the  power  of  throwing  it  into  voluntary  contraction,  which  is  accom- 
panied by  a  feeling  of  pressure  in  the  ear,  and  a  harsh  sound.  The 
function  of  the  stapedius  is  unknown.  Its  contraction  would  tend  to 
press  the  posterior  end  of  the  foot-plate  of  the  stapes  deeper  into  the 
foramen  ovale,  and  cause  the  anterior  end  to  move  in  the  opposite 
direction ;  but  it  is  not  easy  to  see  how  this  would  affect  the  action  of 
the  auditor}'  mechanism. 

The  tensor  tympani  is  supplied  by  the  fifth  nerve  through  a  branch 
from  the  otic  ganglion ;  the  stapedius  is  supplied  by  the  seventh. 
Paralysis  of  the  fifth  nerve  may  be  accompanied  ^\•ith  difficulty  of 
hearing,  especially  for  faint  sounds.  \\Tien  the  seventh  nerve  is 
paralyzed,  increased  sensitiveness  to  loud  sounds  has  been  observed. 

We  have  already  recognized  the  organ  of  Corti,  particularly  the 
hair-cells,  as  a  sensory  epithelium  which  constitutes  the  terminal 
apparatus  of  the  cochlear  nerve.  The  adequate  stimulus  of  the 
auditory  receptors  is  the  periodic  changes  of  pressure  in  the  endo- 
lymph.  But  there  are  various  opinions  as  to  how  these  vibrations 
are  transmitted  to  the  hair-ceUs,  and  as  to  how  the  vibrations  of 
the  hair-cells  are  translated  into  nerve  impulses  in  the  auditory 
fibres.  The  pillars  of  Corti,  the  basilar  membrane,  and  the  mem- 
brana tectoria,  have  in  turn  been  regarded  as  the  structures  im- 
mediately set  into  vibration  by  the  changes  in  the  endolymph. 
The  case  for  the  tectorial  membrane  is  perhaps  the  most  plausible, 
for  its  position  renders  it  most  capable  of  acting  on  the  hairs. 
Others  have  supposed  that  the  hairs  of  the  hair-cells  are  directly 
affected  by  the  endolymph.  Some,  despairing  of  further  analysis, 
content  themselves  with  the  conclusion  that  the  organ  of  Corti 
vibrates  as  a  whole.  Some  of  these  theories  will  be  again  referred 
to  in  considering  what  is  the  greatest  problem  of  the  physiology  of 
hearing,  viz. : 

The  Perception  of  Pitch — ^Analysis  of  Complex  Sounds.— As  the 
eye,  or,  rather,  the  retina  plus  the  brain,  can  perceive  colour,  so  the 
labyrinth  plus  the  brain  can  perceive  pitch.  The  colour-sensation 
produced  by  ethereal  waves  of  definite  frequency  depends  on  that 
frequency;  and  upon  the  frequency  of  the  aerial  vibrations  depends 
also  the  pitch  of  a  musical  note.  But  there  is  this  difference  be- 
tween the  eye  and  the  ear :  that  while  the  sensation  produced  by  a 
mixture  of  rays  of  light  of  different  wave-length  is  always  a  simple 
sensation — that  is,  a  sensation  which  we  do  not  perceive  to  be  built 
up  of  a  number  of  sensations,  which,  in  other  words,  we  do  not 
analyze — the  ear  can  perceive  at  the  same  time,  and  distinguish 


HEARING  1033 

from  each  other,  the  components  of  a  complex  sound.  When  a 
number  of  notes  of  different  pitch  are  sounded  tofjether  at  the 
same  distance  from  the  ear  the  disturbance  which  readies  the  mem- 
brana  tympani  is  the  physical  resultant  of  all  tin-  disturbances  pro- 
duced by  the  individual  notes,  and  it  strikes  up(jn  the  membrane  as 
asinglewave.  '  A  singlecurve  describes  all  that  the  ear  can  possibly 
hear  as  the  result  of  the  most  complicated  musical  performance. 
...  In  the  complicated  sound  the  variations  of  the  pressure  of  the 
air  are  more  abrupt,  more  sudden,  less  smooth,  and  h-ss  distinctly 
periodic  than  they  are  in  softer,  purer,  and  simpler  sound.  But  the 
superposition  of  the  different  effects  is  really  a  marvel  of  marvels  ' 
(Kelvin).  The  ear  or  brain  must,  therefore,  possess  the  power  of 
resolving  the  complex  vibrations  into  their  constituents,  else  we 
should  have  a  mixed  or  blended  sensation,  and  not  a  sensation  in 
which  it  is  possible  to  distinguish  the  constituents  of  which  it  is 
made  up.  Several  hj'potheses  have  been  proposed  to  explain  this 
physiological  analysis  of  sound,  on  the  assumption  that  the  analysis 
takes  place  in  the  labjTinth.  The  most  important,  in  spite  of  certain 
defects,  is  still  that  of  Helmholtz. 

Helmholtz  attempted  to  explain  the  perception  of  pitch  on  the 
assumption  that  in  the  internal  ear  there  exists  a  series  of  resonators, 
each  of  which  is  fitted  to  respond  by  sympathetic  vibration  to  a 
particular  note,  while  the  others  are  unaffected;  just  as  when  a  note 
is  sung  before  an  open  piano  it  is  taken  up  by  the  string  which  is 
attuned  to  the  same  pitch  and  ignored  by  the  rest.  Let  us  sup- 
pose that  a  given  fibre  of  the  auditory  nerve  ends  in  an  organ  which 
is  only  set  vibrating  by  waves  impinging  on  it  at  the  rate  of  100  a 
second,  and  that  the  end-organ  of  another  fibre  is  only  influenced 
by  waves  with  a  frequency  of  200  a  second.  Then,  on  the  doctrine 
of  '  specific  energy  '  (according  to  which  the  sensation  caused  by 
stimulation  of  a  nerve  depends  not  on  the  particular  kind  of  stimu- 
lus but  on  the  anatomical  connection  of  the  nerve  with  certain 
nerve  centres),  in  whatever  way  the  first  fibre  is  excited,  a  sensation 
corresponding  to  a  note  with  a  pitch  of  100  a  second  will  be  per- 
ceived. Whenever  the  second  fibre  is  excited,  the  sensation  will  be 
that  of  a  note  of  200  a  second,  or  the  octave  of  the  first.  If  both 
fibres  are  excited  at  the  same  time  the  two  notes  will  be  heard 
together.  Now,  Hensen  actually  observed  that  in  the  auditory 
organs  of  some  crustaceans,  the  hair-like  processes  of  certain 
epithehal  cells  can  be  set  swinging  by  waves  of  sound,  and.  further, 
that  they  do  not  all  vibrate  to  tlie  same  note  imless  the  sound  is 
very  loud.  In  the  lobster  there  are  between  f(tur  and  five  hundrwl 
of  these  hairs,  varying  in  length  from  14  /z  to  740  /i;  and  in  some 
insects,  such  as  the  locust,  similar  hairs,  also  graduated  in  length, 
exist. 

To  gain  an  anatomical  basis  for  his  theory,  Helmholtz  supposed 


I034  THE  SENSES 

first  of  all  that  the  pillars  of  Corti  were  the  vibrating  structures, 
and  that,  directly  or  through  the  hair-cells,  their  nvechanical  vibra- 
tions were  translated  into  impulses  in  the  auditory  nerve-fibres. 
But  apart  from  the  fact  that  their  number  is  too  small  (about  3,000) 
to  allow  us  to  assign  one  rod  to  each  perceptible  difference  of  pitch, 
and  their  dimensions  too  similar  to  permit  of  the  requisite  range 
of  vibration  frequency,  it  was  pointed  out  that  birds  do  not  possess 
pillars  of  Corti — a  fact  which  was  decisive  against  the  assumption 
of  Helmholtz,  since  nobody  denies  to  singing-birds  the  power  of 
appreciating  pitch.  Helmholtz  accordingly,  choosing  between  the 
remaining  possibilities,  gave  up  the  pillars  of  Corti,  and  adopting 
a  suggestion  of  Hensen,  substituted  the  radial  fibres  of  the  basilar 
membrane  as  his  hypothetical  resonators.  These  are  more  ade- 
quate to  the  task  imposed  on  them,  since  their  range  of  length  is 
far  greater  (41  ju  at  the  base  to  495  fj,  at  the  apex  of  the  cochlea — 
Hensen);  and  the  elaborate  structure  of  Corti's  organ  certainly 
suggests  that  some  one  or  other  of  its  elements  may  be  endowed 
with  such  a  function.  Experimentally,  too,  it  has  been  shown 
that  destruction  of  the  apex  of  the  cochlea  causes  loss  of  appreciation 
of  low  notes,  and  destruction  of  the  base  loss  of  appreciation  of  high 
notes,  which  agrees  with  Helmholtz's  view.  But  while  the  theory 
of  peripheral  analysis  of  pitch  tends  upon  the  whole  to  be  strength- 
ened as  evidence  gathers,  it  is  possible  that  the  analysis  is  accom- 
plished in  some  other  way  than  by  sympathetic  resonance. 

Ewald  has  developed  a  theory  according  to  which  each  note  causes 
the  basilar  membrane  to  vibrate  throughout  its  whole  extent  in  such 
a  way  that  stationary  waves  are  produced  in  it,  like  the  Chladni's 
figures  seen  on  a  metal  plate  strewed  with  sand  when  it  is  set  into 
vibration.  The  pattern  of  the  movement,  the  '  sound-picture,'  will  be 
different  for  each  tone,  since  the  interval  between  the  waves  will  be 
different.  The  hair-cells  and  auditory  fibres  of  particular  parts  of  the 
organ  of  Corti  will  therefore  be  stimulated  by  the  pressure  of  the  mem- 
brane, or  escape  stimulation,  according  to  the  position  of  the  stationary 
waves  with  reference  to  them  for  each  note.  In  this  way  each  sound- 
picture  will  be  printed,  so  to  speak,  upon  the  sensitive  terminal  appa- 
ratus of  the  auditory  nerve,  as  a  letter  is  printed  upon  a  piece  of  paper 
by  a  type.  The  corrcs])onding  excitation  pattern — i.e.,  the  particular 
distribution  of  cochlear  fibres  stimulated — is  supposed  to  be  associated 
in  consciousness  with  the  appreciation  of  the  pitch  of  the  particular 
note.  Ewald  has  endeavoured  to  support  his  theory  by  showing  that 
fine  membranes  of  the  dimensions  of  the  basilar  membrane  do  yield 
very  distinct  sound-pictures  for  different  simple  tones  as  well  as  for 
complex  tones.  These  can  be  observed  with  the  microscope  and  photo- 
graphed (Fig.  440). 

One  of  the  best-known  theories  of  central  analysis  may  be  con- 
veniently labelled  the  'telephone  theory,'  in  accordance  with  the  simile 
used  by  Rutherford.  He  suppo.sed  that  the  organ  of  Corti  (or  at  any 
rate  the  hair-cells)  is  set  into  vibration  as  a  whole  by  all  audible  sounds, 
and  that  its  vibrations  are  translated  into  impulses  in  the  auditory 
nerve,  which  are  the  physiological  counterpart  of  "th^;  aerial  waves 
and   the  waves  of  increased   and   diminished   prcsoure  in  the  liquids 


SMI./.L  ASlJ   lA^lE 


i«35 


of  the  labyrinth  to  wliicFi  tlu-y  give  rise.  Tliiis,  a  buund  of  loo 
vibrations  a  second  wonld  start  loo  impulses  a  second  in  tlie  auditory 
nerve;  a  loud  sound  would  set  up  impulses  more  intense  tlian  a 
feeble  sound;  and  a  comiilcx  wave,  which  is  the  resultant  of  several 
sounds  of  different  vibration-frequency,  would  also  in  some  way  or 
other  stamp  the  impress  of  its  form  on  the  auditory  excitation  wave; 
just  as  in  a  telephone  every  wave  in  the  air  causes  a  swing  of  the 
vibrating  plate,  and  llius  sets  up  a  current  of 
corrcspon<ling  intensity  and  duration  in  the 
wires.  This  theory  evidently  abandons  the 
doctrine  of  specific  energy  for  the  particular 
case  of  the  analysis  of  pitch,  for  it  assumes 
that  differences  of  auditory  sensation  are 
related  to  differences  in  the  nature  of  the  im- 
pulses travelling  up  the  auditory  nerve,  and 
not  merely  to  differences  in  the  anatomical 
connections  (peripheral  and  central)  of  thd 
auditory  nerve-fibres.  It  is  unsatisfactory 
because  it  takes  no  account  of  the  remarkable 
and  suggestive  structure  of  the  telephone  plate 
— i.e.,  of  the  organ  of  Corti — and  gives  no  hint 
of  how  the  analysis  is  accomplished  in  the 
central  organ. 

The  range  of  hearing  is  very  great.  The 
highest  audible  tone  corresponds  to  30,000  to 
40,000  vibrations  a  second,  the  lowest  to  about 
30.  Between  these  limits  as  many  as  6,000 
variations  of  pitch  can  be  perceived. 

Wien  has  elaborately  investigated  the  question  how  the  sensitive- 
ness of  the  ear  varies  for  tones  of  different  pitcli .  A  tone  of  50  vibrations 
a  second,  in  order  to  be  just  heard,  mu.st  have  an  intensity  corre- 
sponding to  about  100  million  times  as  much  energy  as  is  needed  for  a 
tone  of  2,000  vibrations.  It  is  only  on  the  extraordinary  sensibility 
of  the  ear  for  the  range  of  tones  used  in  ordinarv  speech  that  the 
possibility  of  understanding  speech  depends  when  the  circumstances 
are  unfavourable — e.g.,  at  a  great  distance,  or  in  the  presence  of  much 
stronger  accompanying  noises. 


Fig.  4.40. — Photograph  of  a 
Sound-Picture  (Ewald). 


Section  III. — Smell  and  Taste. 

Smell  was  defined  by  Kant  as  '  taste  at  a  distance  ' ;  and  it  is 
obvious  that  these  two  senses  not  only  form  a  natural  group  when 
the  quality  of  the  sensations  is  considered,  but  are  closely  associated 
in  their  physiological  action,  especially  in  connection  with  the 
perception  of  the  flavour  of  the  food.  Their  intimate  relation  is 
further  indicated  by  the  fact  that  the  cortical  areas  in  which  smell 
and  taste  are  represented  lie  close  together  or  overlap  each  other 
on  the  gyrus  hippocampi  and  uncus  (p.  933).  The  olfactory  end- 
organs  in  the  mucous  membrane  of  the  upper  part  of  the  nostrils, 
the  so-called  regio  olfactoria,  liave  been  already  described  (p.  So3)- 
In  cases  of  anosmia,  in  wliich  the  olfactory  nerve  is  absent  or 
paralyzed,  emell  is  abolished;  but  substances  such  as  ammonia  and 
acetic  acid,  which  stimulate   the  ordinary  sensory  nerves  (nasal 


I036  THE  SENSES 

branch  of  fifth)  of  the  olfactory  mucous  membrane,  are  still  per- 
ceived, though  not  distinguished  from  each  other.  In  fact,  the 
so-called  pungent  odour  of  these  substances  is  no  more  a  true  smell 
than  the  sense  of  smarting  they  produce  when  their  vapour  comes 
in  contact  with  a  sensory  surface  like  the  conjunctiva,  or  a  piece 
of  skin  devoid  of  epidermis. 

It  was  at  one  time  believed  that  odoriferous  particles  could  not 
be  appreciated  unless  they  were  borne  by  the  air  into  the  nostrils; 
but  this  appears  not  to  be  the  case,  for  the  smell  of  substances 
dissolved  in  physiological  salt  solution  is  distinctly  perceived  when 
the  nostrils  are  filled  with  the  liquid;  and  fish,  as  every  line-fisher- 
man knows,  have  no  difficulty  in  finding  a  bait  in  the  dark. 

The  substances  which  can  affect  the  olfactory  mucous  membrane 
can  be  divided  into  four  groups : 

1.  Those  which  act  only  on  the  olfactory  nerves,  the  odours 

proper. 

2.  Substances  which  act  at  the  same  time  on  olfactory  nerves, 

and  on  nerves  of  common  sensation  (tactile  nerves) — 
e.g.,  acetic  acid. 

3.  Substances  which  act  at  the  same  time  on  the  gustatory 

nerves. 

4.  Substances    which    act    only   on    the    nerves    of   common 

sensation  (tactile  nerves) — e.g.,  carbon  dioxide. 

Zwaardemaker  has  classified  the  pure  odours  as  follows: 

(i)  Ethereal  odours,  as  those  of  fruits;  (2)  aromatic  odours,  as  of 
camphor  or  bitter  almonds;  (3)  fragrant  odours,  as  of  flowers;  (4)  am- 
brosial odours,  as  of  amber  or  musk;  (5)  garlic  odours,  as  of  onion, 
garlic,  asafoetida;  (6)  empyreumatic,  or  burning  odours,  as  of  burnt 
coffee  or  tobacco  smoke;  (7)  caprylic  or  goat  odours,  as  of  sweat; 
(8)  repulsive  odours,  as  the  odour  of  the  disease  ozaena;  (9)  nauseating 
odours,  as  of  faeces  or  putrefying  material. 

The  most  interesting  form  of  inadequate  stimulation  is  electrical 
excitation  of  the  olfactory  mucous  membrane,  which  causes  a  sensation 
like  the  smell  of  phosphorus.  The  sensation  is  experienced  at  the 
kathode  on  closure  and  the  anode  on  opening.  As  to  the  manner  in 
which  the  multitudinous  adequate  stimuli  excite  the  olfactory  nerves, 
we  can  only  suppose  that  they  act  as  chemical  stimuli.  Smell  and 
taste  are  pre-eminently  the  '  chemical  '  senses,  as  sight  and  hearing  are 
pre-eminently  '  physical  '  senses.  But  little  is  known  of  the  relation 
between  the  chemical  constitution  or  physical  properties  of  substances 
and  the  quality  of  the  odoriferous  sensation  which  they  excite,  although 
Haycraft  has  pointed  out  some  interesting  relations  between  the  atomic 
weights  of  certain  elements  and  their  power  of  exciting  odours.  The 
number  of  distinct  odours  which  can  be  perceived  is  so  great  that  it  is 
scarcely  conceivable  that  each  is  subserved  by  special  olfactory  fibres. 
Marked  changes  occur  in  disease,  and  all  odours  need  not  be  affected 
to  the  same  extent.  Some  may  be  alrhost  normally  perceived,  while 
relative  or  complete  loss  of  smell  exists  as  regards  others.  These  and 
other  facts  have  given  rise  to  the  idea  that  there  are  several  groups  of 
olfactory  fibres,  each  concerned  in  the  appreciation  of  a  particular 
odour  or  group  of  odours.  Yet  it  has  not  proved  possible  to  reduce 
them  to  a  limited  number  of  fundamental  odours  and  their  combina- 
tions. 

Acuteness  of  smell  may  be  measured  by  arrangements  called  olfac 


SMELL  AND  TASTli  1037 

tometers.  Zwaardemaker's  olfactometer  consists  of  a  piece  of  india- 
rubber  tubinf;  fitted  inside  a  plass  tube,  through  which  air  is  drawn 
into  the  nostrils.  Another  glass  tube  just  fitting  the  rubber  tube  is 
pushed  inside  it,  so  as  to  cover  a  portion  of  it.  'I  lie  inininuim  amount 
of  surface  of  tiie  in<liarubber  tube  whicii  must  be  left  cxjjo.sed  so  that 
the  smell  of  the  rubber  may  be  percei\cd  is  a  measure  of  the  acutcness 
of  smell.  To  investigate  other  odours  tubes  of  the  corresponding 
odorous  substances  can  be  constructed. 

Taste. — The  sense  of  taste  is  not  so  strictly  localized  as  the  sense 
of  smell.  The  tip  and  sides  of  the  tongue,  its  root,  the  neighbour- 
ing portions  of  the  soft  palate,  and  a  strip  in  the  centre  of  the  dorsum, 
are  certainly  endowed  with  the  sense  of  taste;  but  the  exact  limits  of 
the  sensitive  areas  have  not  been  defined,  and,  indeed,  vary  in 
different  individuals. 

The  nerves  of  taste  are  the  glosso-pharyngeal,  which  innervates  the 
posterior  part  of  the  tongue,  and  the  lingual,  which  supplies  its  tip 
(see  p.  896).  The  end-organs  of  the  gustatory  nerves  are  the  taste- 
buds  or  taste-bulbs,  which  stud  the  fungiform  and  circumvallate 
papilke,  and  are  most  characteristically  seen  in  the  moats  surrounding 
the  latter.  They  are  barrel-like  bodies,  the  staves  of  the  barrel  being 
represented  by  supporting  cells;  each  bud  encloses  a  number  of  gusta- 
tory cells  with  fine  processes  at  their  free  ends  projecting  through  the 
superficial  end  of  the  barrel.  They  are  surrounded  by  the  end  arboriza- 
tions of  the  fibres  of  the  gustatory  nerves.  Taste-buds  are  also  found 
on  the  posterior  surface  of  the  epiglottis  and  in  the  larynx.  It  has 
been  suggested  that  these  form  the  afferent  end-organs  of  a  reflex 
apparatus  which  guards  the  glottis  against  the  entrance  of  food  in 
deglutition  (WUson).  Epithelial  buds,  different  from  the  olfactory 
elements,  also  occur  in  the  olfactory  region  of  the  nasal  mucous  mem- 
brane. It  is  possible  that  the  so-called  nasal  taste — e.g.,  the  sweet 
taste  caused  by  chloroform  when  aspirated  in  not  too  small  an  amount 
through  the  nose — depends  upon  these  buds. 

As  to  the  properties  in  virtue  of  which  sapid  substances  are 
enabled  to  stimulate  the  gustatory  nerve-endings,  we  know  that 
they  must  be  soluble  in  the  liquids  of  the  mouth,  and  there  our 
knowledge  ends.  An  attempt  has  been  made  by  various  authors 
to  connect  the  taste  of  such  bodies  with  their  chemical  composition, 
but  researches  of  this  kind  have  not  hitherto  yielded  much  fruit. 
The  number  of  distinct  qualities  of  taste  sensation  is  considerable, 
but  by  no  means  so  great  as  the  number  of  qualities  of  olfactory 
sensations,  and  they  are  more  easily  reduced  to  a  few  primary  or 
fundamental  sensations.  Sapid  substances  have  generally  been 
divided  into  four  classes  as  regards  the  fundamental  sensations  pro- 
duced by  them— viz. :  (i)  Sweet,  (2)  acid,  (3)  bitter,  {4)  sahnei 
All  taste  sensations  seem  to  be  combinations  of  these,  or  combina- 
tions of  one  or  more  of  them  with  olfactory  sensations,  or  with  sensa- 
tions due  to  excitation  of  the  ordinary  sensory  nerves  of  the  tongue. 

Sweet  and  acid  tastes  are  best  appreciatwl  by  the  tip,  and  bitter 
tastes  by  the  base,  of  the  tongue.  Differences  have  been  detected 
between  individual  papilhe  in  their  i)ower  of  reaction  to  sapid  sub- 


I038  THE  SENSES 

stances  which  produce  one  or  other  of  the  fundamental  sensations. 
Of  125  fungiform  papillae  tested  with  solutions  of  tartaric  acid,  sugar, 
and  quinine,  27  gave  no  sensation  of  taste.  Tartaric  acid  evoked 
its  acid  taste  in  91  of  the  remaining  98,  sugar  its  sweet  taste  in  79, 
and  quinine  its  bitter  taste  in  71 ;  12  reacted  only  to  tartaric  acid, 
and  3  only  to  sugar  (Ohrwall).  Such  facts  indicate,  although  they 
do  not  definitely  prove,  the  existence  of  specific  receptors  for  each 
of  the  fundamental  taste  sensations — i.e.,  gustatory  end-organs, 
which  are  easily  excited  by  an  adequate  stimulus  (acid,  e.g.,  in  the 
case  of  an  '  acid  '  taste-bud),  with  difficulty  or  not  at  all  by  an  in- 
adequate stimulus. 

The  form  of  inadequate  stimulation  most  investigated  is  that  pro- 
duced when  a  constant  current  is  passed  through  the  tongue.  An  acid 
taste  is  experienced  at  the  positive,  and  an  alkaline  or  bitter  taste  at  the 
negative  pole;  and  this  is  the  case  even  when  the  current  is  conducted 
to  and  from  the  tongue  by  unpolarizable  combinations,  which  prevent  the 
deposition  of  electrolytic  products  on  the  mucous  membrane  (p.  705). 
The  sensations  are  due  to  stimulation  of  the  gustatory  end-organs  and 
not  of  the  nerve -trunks. 

Normal  lymph,  which  bathes  these  end-organs,  does  not  excite  any 
sensation  of  taste,  but  when  the  composition  of  the  blood  is  altered  in 
disease  or  by  the  introduction  of  foreign  substances,  tastes  of  various 
kinds  may  be  perceived.  Sometimes  this  may  be  due  to  the  stimula- 
tion of  substances  excreted  in  the  saliva;  but  in  other  cases  it  seems 
that,  without  passing  bej'ond  the  blood  and  lymph,  foreign  substances 
may  excite  the  gustatory  nerves. 

Flavour  embraces  a  group  of  mixed  sensations  in  which  smell  and 
taste  are  both  concerned,  as  is  shown  by  the  common  observation  that 
a  person  suffering  from  a  cold  in  the  head,  which  blunts  his  sense  of 
smell,  loses  the  proper  flavour  of  his  food,  and  that  some  nauseous 
medicines  do  not  taste  so  badly  when  the  nostrils  are  held. 

In  common  speech,  the  two  sensations  are  frequently  confounded 
with  each  other  and  with  tactile  sensations.  Thus  the  '  bouquet  '  of 
wines,  which  most  people  imagine  to  be  a  sensation  of  taste,  is  in 
reality  a  sensation  of  smell ;  the  astringent  '  taste  '  of  tannic  acid  is  not 
a  taste  at  all,  but  a  tactile  sensation;  the  '  hot  '  taste  of  mustard  is  no 
more  a  true  sensation  of  taste  than  the  sensation  produced  by  the 
same  substance  when  applied  in  the  form  of  a  mustard  poultice  to 
the  skin. 

Section  IV.- — Cutaneous  and  Internal  Sensations. 

Under  the  sense  of  touch  it  was  at  one  time  usual  to  include  a 
group  of  sensations  which  differ  in  quality — and  that  in  some  in- 
stances to  as  great  an  extent  as  any  of  the  sensations  which  are 
universally  considered  as  separate  and  distinct — but  agree  in  this, 
that  the  end-organs  by  which  they  are  perceived  are  all  situated  in 
the  skin,  the  mucous  membranes,  or  the  subcutaneous  tissue. 
They  are  more  correctly  designated  'cutaneous  sensations.'  Such 
are  the  common  tactile  sensations — including  pressure,  tickling, 
and  itching — and  the  sensations  »f  temperature,  or,  more  correctly, 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


1039 


of  change  of  lemperature,  or  of  warmth  and  cold.  The  sensation 
of  pain,  altlunigh  it  cannot  Ix-  absolutely  separated  from  these,  ought 
not  to  l)e  grouped  along  with  them.  It  is  called  forth  by  thestinmlu- 
tion  of  afferent  nerve-hbres  in  their  course;  and  it  may  originate, 
under  certain  conditions,  in  internal  organs  which  are  devoid  of 
tactile  sensibility,  and  the  functional  activity  of  which  in  their 
normal  state  gives  rise  to  no  special  sensation  at  all.  The  peculiar 
sensation  associated  with  voluntary  nmscular  effort,  to  which  the 
name  of  the  muscular  sense  has  been  given,  also  deserves  a  separate 
place;  for  although  it  may  in  part  depend  on  tactile  sensations  set 
up  through  the  medium  of  end-organs  situated  in  nmscle,  tendon, 
or  the  structures  which  enter  into  the  formation 
of  the  joints,  other  elements  are,  in  all  proba- 
bility, involved. 

The  simplest  form  of  tactile  sensation  is  that 
of  mere  contact,  as  when  the  skin  is  lightly 
touched  with  the  blunt  end  of  a  pencil.  This 
soon  deepens  into  the  sensation  of  pressure  if  / 
the  contact  is  made  closer;  and  eventually  the 
sense  of  pressure  merges  into  n  feeling  of  pain. 
Most  physiologists  agree  that  in  the  skin  itself 
four  fundamental  qualities  of  sensation  are  re- 
presented— touch  in  tlvc  restricted  sense  (the 
sensation  elicited  by  light  contact),  warmth, 
cold,  and  pain.  Pressure  is  mainly  a  sensation 
connected  with  the  stimulation  of  structures 
deeper  than  the  skin — e.g.,  the  sensation  of 
contact  is  abolished  in  cicatrices  where  the 
true  skin  has  been  destroyed,  while  sensibility 
to  pressure  persists — although  the  sensation  of 
light  pressure  may  be  to  some  extent  re- 
presented in  the  skin  itself  in  association 
with  touch.  In  a  somewhat  diagrammatic 
sense  it  may  be  said  that  the  surface  of  the  skin  is  divided  into  a 
great  number  of  very  small  areas,  each  of  which  is  related  especially 
to  one  or  other  of  the  four  fundamental  sensations.  Areas  con- 
cerned in  one  sensation  are  everywhere  mingled  with  areas  con- 
cerned in  the  others.  By  appropriate  methods  it  has  been  found 
possible  to  determine  the  existence  on  the  skin  of  the  trunk  and 
limbs  of  not  less  than  30,000  '  warm-spots,'  which  alwa\s  react  to 
stimulation  by  a  sensation  of  warmth;  250,000  '  cold-spots,'  which 
react  by  a  sensation  of  cold;  and  half  a  million  touch-spots,  whose 
specific  reaction  is  a  sensation  of  touch.  It  is  more  difficult  to 
localize  definitely  bounded  '  pain-spots,'  partly  because  of  the  very 
rich  sup|)l\'  of  pain-fibrrs  to  the  skin.  Yet  1  here  is  reason  to  believe 
that  pain,  like  touch,  warmth,  and  cold,  is  subserved  by  separate 


Fig.  441. — Tastile  Cor- 
puscle from  Skin  of 
Finger  (Sniirnow). 
(Golgi  preparation.) 
The  winding  and  in- 
tersecting black  lines 
are  the  non-medul- 
lated  endings  of  the 
one  or  more  nerve- 
fibres  that  enter  the 
corpuscle. 


I040  THE  SENSES 

receptors.  The  simplest  assumption  which  will  satisfactorily 
account  for  the  distribution  of  the  four  fundamental  cutaneous 
sensations  is  that  the  skin  is  supplied  with  four  kinds  of  nerve- 
fibres,  anatomically  as  well  as  functionally  distinct.  Some  fibres 
minister  to  the  sensation  of  cold,  others  to  that  of  warmth,  others 
to  that  of  touch,  and  others  still  to  pain.  And  just  as  stimulation 
of  the  optic  nerve  gives  rise  to  a  sensation  of  light,  so  stimulation 
of  any  one  of  the  cutaneous  nerves  gives  rise  to  the  specific  sensa- 
tion proper  to  the  group  to  which  It  belongs.  The  existence  of 
different  forms  of  sensory  end-organs  in  the  skin  and  other  tissues 
(tactile  or  touch-corpuscles,  corpuscles  of  Pacini,  end-bulbs  of 
Krause,  etc.)  points  in  the  same  direction.  The  end-organs  of  the 
touch  sensations  are  believed  to  be  the  ring-like  arrangements  of 
non-medullated  nerve-fibres  encircling  the  hair-follicles,  and  in 
parts  of  the  skin  devoid  of  hairs  the  corpuscles  of  Meissner  (v.  Frey). 

Touch-spots  can  easily  be  demonstrated  by  touching  the  skin  lightly 
with  some  small  object  such  as  a  hair.  The  most  exact  quantitative 
observations  have  been  made  by  means  of  v.  Frey's  hair  aeslliesiometer. 
This  consists  of  a  handle  in  which  hairs  of  different  diameters  can  be 
fixed.  The  area  of  the  cross  section  of  each  hair  is  measured  under  the 
microscope,  and  the  pressure  necessary  to  bend  it  is  determined  by 
pressing  it  upon  the  scale-pan  of  a  balance.  The  pressure  in  milli- 
grammes, divided  by  the  cross  section  in  square  millimetres,  gives  the 
pressure  per  square  millimetre,  which,  according  to  v.  Frey,  permits 
hairs  to  be  chosen  so  as  to  give  a  uniform  intensity  of  stimulation  or  a 
variable  intensity,  according  to  the  object  of  the  investigation.  Many 
observers,  however,  believe  that  it  is  more  accurate  to  take  no  account 
of  the  pressure  per  unit  of  area,  but  to  graduate  the  hairs  according  to 
the  total  pressure  needed  to  bend  them.  Wlien  touch-spots  ascer- 
tained in  this  way  are  excited  by  an  inadequate  stimulus— e.^.,  an 
alternating  current  of  minimal  strength,  applied  by  the  unipolar 
method  through  the  head  of  a  pin  as  an  electrode — they  still  respond 
by  their  characteristic  or  specific  reaction — namely,  a  sensation  of 
touch — in  the  case  supposed,  a  vibrating  sensation  like  that  caused  by 
a  tuning-fork  in  contact  with  the  skin.  In  the  spaces  between  the 
touch-spots  the  sensation  produced  by  the  same  strength  of  current,  or 
even  by  a  weaker  current,  is  not  one  of  touch,  but  a  painful  pricking 
sensation  which  has  no  vibratory  character,  but  is  permanent  as  long 
as  the  current  lasts. 

The  spots  most  sensitive  to  touch  lie  close  to  the  hairs  on  their 
'  windward  '  side — i.e.,  on  the  side  away  from  which  they  slope.  The 
minimum  pressure  necessary  to  evoke  a  sensation  of  contact  is  not  the 
same  for  every  portion  of  the  skin.  The  forehead  and  palm  of  the 
hand  are  most  sensitive. 

If  two  points  of  the  skin  are  touched  at  the  same  time  there  is  a 
double  sensation  when  the  distance  between  the  points  exceeds  a  cer- 
tain minimum,  which  varies  for  different  parts  of  the  sensitive  surface. 

Practice  increases  the  acuity  of  touch  for  the  two  points  test.  Even 
in  a  few  hours  it  may  be  temporarily  quadrupled  on  some  parts  of  the 
skin.  Since  at  the  same  time  it  is  increased  in  the  corresponding  part 
of  the  opposite  side  of  the  body,  it  is  argued  that  the  modification  takes 
place  in  the  central  norvous  system,  not  in  the  end-organs  themselves. 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


104I 


Few  of  the  internal  organs  are  supplied  with  tactile  nerves.  The 
mucous  membrane  of  the  alimentary-  canal  from  the  upper  end  of  the 
oesophagus  to  the  junction  of  the  rectum  with  the  anal  canal  is  in- 
sensitive to  tactile  stimulation  (Hertz).  The  movements  of  a  taje- 
worm  in  the  intestines  are  not  recognized  as  tactile  sensations,  nor  the 
movements  of  the  alimentary  canal  during  digestion,  nor  the  rubbing 
of  one  muscle  on  another  during  its  contraction. 


Number  of  Touch- 
Spou  per  Sq.  Cm. 

1 
Mean  Threshold  Valuei 
.     Grammes 
Sq.  Mm. 

Wrist  (ventral  surface) 

28 

I*I 

Wrist  (dorsal  surface)   .         -         - 

28 

1-2 

Forearm       -         -         -         -         . 

16 

1-2 

Elbow  ------ 

12 

i'3 

Upper  arm 

10 

1-4 

Foot  (dorsal  surface)     .         -         . 

23 

I'2 

Leg  (ventral  surface)     -         -         - 

5 

2'I 

Thigh  (ventral  surface) 

14 

1-3 

Breast  ------ 

21 

2-7 

Back 

26 

4-3 

(Kiesow). 

Pressure  is  only  perceived  when  it  affects  two  neighbouring  areas  to 
a  di^erent  degree.  Thus,  the  atmospheric  piessure,  bearing  uniformly 
on  the  whole  surface  of  the  body,  causes  no  sei  salion ;  we  are  so  entirely 
unconscious  of  it  that  it  needed  the  inspiration  of  genius  to  discover 
it,  and  the  persistence  of  genius  to  force  the  discovery  on  the  world. 
When  the  finger  is  dipped  in  a  trough  of  mercury  at  its  own  temperature, 
no  sensation  is  perceived  except  a  feeling  of  constriction  at  the  surface 
of  the  liquid.  The  perception  of  light  pressure  and  of  the  form  and  size 
of  objects  in  contact  with  the  skin  is  believed  to  be  due  to  the  touch- 
spots.  Deep  pressure,  however,  is  appreciated,  not  by  the  skin,  but 
through  sensory  end-organs  in  deeper  structures — probably,  e.g., 
Pacini's  corpuscles  and  the  muscle-spindles  (Fig.  448,  p.  1053). 


Distance  at  which  Two  Points 

can  he  distinctly  felt,  in  Mm. 

Point  of  tongue    - 

I-X 

Palmar  surface  of  third 

phalanx  of  finger 

2'3 

Dorsal  surface  of  tliird 

phalanx  of  finger 

6-7 

Tip  of  nose  - 

6-7 

Back    -         -         -         - 

II-.: 

Eyelids          .         -         - 

ii-i 

Skin  over  sacrum 

40-5 

Upper  arm  -         -         - 

67-6 

Sensations  of  Warmth  and  Cold.-  A\'hcn  a  body  colder  or  hotter 
han  the  skin  is  placed  on  it,  or  when  heat  is  in  any  other  way 

66 


1042 


THE  SENSES 


withdrawn  from  or  imparted  to  the  cutaneous  tissues  with  sufficient 
abruptness,  a  sensation  of  cold  or  warmth  is  experienced.  And 
when  two  portions  of  the  skin  at  different  temperatures  are  put  in 
contact,  we  feel  that,  relatively  to  one  another,  one  is  warm  and 
the  other  cold.     But  it  is  worlhy  of  remark  that  it  is  only  difference 

of  temperature  (or,  perhaps,  rather  the 
rate  at  which  heat  is  being  gained  or 
lost  by  the  skin),  and  not  absolute 
height,  which  we  are  able  to  estimate 
by  our  sensations.  Thus,  a  hand  which 
has  been  working  in  ice-cold  water  will 
feel  water  at  10°  C.  as  warm ;  whereas  it 
would  appear  cold  to  a  warm  hand. 

Blix,  Goldscheider,  and  others  have 
shown  that  the  whole  skin  is  not  en- 
dowed with  the  capacity  of  distin- 
guishing temperature,  but  that  the 
temperature  sensations  are  confined 
to  minute  areas  scattered  over  the 
cutaneous  surface.  The  great  majority 
of  these  are  '  cold  '  spots — i.e.,  respond 
to  stimulation  only  by  a  sensation  of 
cold  —  while  a  smaller  number  are 
*  warm  '  spots,  and  respond  only  by  a 
sensation  of  warmth  (Fig.  442).  These 
spots  can  be  mapped  out  by  bringing 
into  contact  with  the  skin  small  pieces 
of  wire  at  a  temperature  a  few  degrees 
above  or  below  that  of  the  skin.  With 
such  mild  stimuli  a  response  can 
generally  be  obtained  only  from  one 
kind  of  spot — that  is,  the  cold  wire 
stimulates  only  the  cold  and  not  the 
warm  spots,  and  vice  versa — but  with 
much  more  intense  thermal  stimuli — 
say,  temperatures  of  45°  to  50°  C. — 
not  only  do  the  warm  spots  respond 
with  the  appropriate  sensation,  but 
the  cold  spots  respond  with  a  sensation 
of  cold.  This  is  well  seen  when  a 
beam  of  sunlight  is  focussed  succes- 
sively on  a  warm  and  a  cold  spot.  Inadequate  stimuli  (mechanical 
and  electrical)  also  evoke  the  specific  response  of  warmth  from 
warm  spots,  and  of  cold  from  cold  spots. 

When  the  hand  is  put  into  water  at  the  temperature  of  the  skin, 
and  the  water  slowly  heated,  the  warm  spots  are  at  first  alone  stimu- 


Fig.  442. — 'Warm'  and  'Cold' 
Areas  on  Skin  (Goldscheider). 
The  areas  are  mapped  out  on 
the  palm  of  the  left  hand.  In 
the  upper  figure  the  relative 
sensitiveness  to  warmth  is 
represented  by  the  depth  of  the 
shading,  the  black  areas  being 
most  sensitive,  then  the  lined 
areas,  then  the  dotted,  and 
last  of  all  the  white  ai^eas.  In 
the  lower  figure  the  relative 
sensitiveness  to  cold  stimuli  is 
shown  in  the  same  way. 


CUTANEOUS  AND  INTERNAL  SENSATIONS  1043 

lated,  and  the  sensations  of  lukewarm  and  then  of  warm  are  experi- 
snced.  When  the  temperature  of  the  water  reaches  45°  C.,  the 
quahty  of  the  sensation  changes  to  '  hot.'  At  a  still  higher  tempera- 
ture the  sensation  becomes  painful  or  burning.  The  most  probable 
explanation  of  these  facts  is  mentioned  below  (p.  1044). 

It  is  not  only  of  physiological  interest,  but  of  practical  imix)rtance, 
that  most  mucous  membranes  arc  in  comparison  witli  the  skin  but 
slightly  sensitive  to  changes  of  temperature.  Only  towards  tlie  ends 
of  the  alimentary  canal,  in  the  mouth,  pharynx,  oesophagus,  and  anal 
canal,  is  it  possible  to  elicit  warmth  or  cold  sensations.  '1  here  is  some 
difference  of  opinion  wliether  a  blunted  scnsibihty  appears  in  the 
stomach  also.  The  uterus,  too,  is  quite  insensible  to  moderate  heat; 
and  hot  liquids  may  be  injected  into  its  cavity  at  a  temperature  higher 
than  that  which  can  be  borne  by  the  hand,  without  causing  inconveni- 
ence— a  fact  which  finds  its  application  in  the  practice  of  gj-na'colog>' 
and  obstetrics.  It  is,  indeed,  obvious  that  in  the  greater  number  of 
the  internal  organs  the  conditions  necessary  for  stimulation  of  tem- 
perature nerves,  even  if  such  were  present,  could  Jiardly  ever  exist. 

It  has  already  been  mentioned  that  changes  of  external  temperature 
exert  a  remarkable  influence  on  the  intensity  of  metabobsm  (p.  668), 
and  it  has  been  supposed  that  this  is  brought  about  by  afferent  impulses 
travelHng  up  the  cutaneous  nerves.  Wo  have  also  seen  that  for  certain 
kinds  of  stimuli  the  excitability  of  nerve-fibres  is  increased  by  cooling 
(p.  758).  It  is  possible  that  this  is  the  case  for  the  fibres  in  the  skin 
which  arc  concerned  in  the  regulation  of  the  production  of  heat,  and  it 
has  been  suggested  that  this  fact  may  have  a  bearing  on  the  reflex 
regulation  of  temperature  (Lorrain  Smith). 

Pain  Sensations. — While  the  cold  and  the  warmth  spots  are  irregu- 
larly distributed  over  the  skin  in  more  or  less  compact  groups,  and 
the  touch  sensations  are  intimately  associated  with  the  hair  follicles, 
the  pain  spots  are  more  uniformly  spread,  and  at  the  same  time  set 
closer  together.  In  parts  of  the  body  where  but  one  of  these 
elementary  forms  of  general  sensibility  is  present,  as  in  the  central 
parts  of  the  cornea  and  in  the  dentine  and  pulp  of  the  teeth,  it  is 
always  pain. 

In  certain  situations  pain  and  temperature  sensibility  are  found 
together,  but  not  touch — e.g.,  at  the  margin  of  the  cornea  and  on 
the  conjunctiva. 

In  general,  the  skin  is  far  more  sensitive  to  pain  than  the  deeper 
structures.  The  most  painful  part  of  an  o])eration  is  generally  the 
stitching  of  the  wound.  The  cutting  of  healthy  muscle  causes  no 
pain.  In  an  operation  in  which  an  artificial  connection  was  estab- 
lished between  the  stomach  and  the  small  intestine  (gastro- enter- 
ostomy), and  in  which  no  anesthetic  was  administered,  the  only 
pain  of  which  the  patient  complained  was  produced  by  the  incision 
in  the  skin  (Sonn).  This,  however,  does  not  prove  that  the 
abdominal  viscera  are  devoid  of  pain  nerves,  for  it  has  been  shown 
in  animals  that  exposure  of  the  intestines,  etc.,  as  in  laparotomy, 
leads  to  a  rapid  depression  (exhaustion  ?)  of  the  sensibility  for  pain 


I044  THE  SENSES 

(Kast  and  Meltzer).  In  the  intact  animal  and  human  being  painful 
impressions  can  unquestionably  be  excited  in  the  viscera  by  adequate 
stimuli  (p.  873).  Thus,  the  spasmodic  contraction  of  the  intestines 
and  stomach  causes  the  intense  pain  of  colic  and  gastralgia.  Labour 
is  an  example  of  a  strictly  physiological  function  which  is  the 
occasion  of  severe  pain.  It  would  appear  from  the  observations 
of  Hertz  that  the  only  immediate  cause  of  true  visceral  pain,  as 
distinguished  from  referred  pain  (p.  863)  is  distension  acting  on  the 
muscular  coat  of  hollow  organs  and  on  the  fibrous  capsule  of  solid 
organs.  The  sensation  of  pain  in  the  alimentary  canal  is  due  to  a 
more  rapid  or  a  greater  distension  than  that  which  constitutes  the 
adequate  stim.ulus  for  the  sensation  of  fulness.  Visceral  sensi- 
bility seems  to  be  exaggerated  in  such  conditions  as  hypochondri- 
asis, neurasthenia,  and  anaemia.  Tissues  normally  insensible,  or, 
rather,  but  slightly  sensible,  to  pain  may  become  acutely  painful 
when  inflamed. 

The  question  has  been  raised  whether  the  sensation  of  pain  can 
be  caused  by  excessive  stimulation  of  the  nerves  of  common  tactile 
sensibility,  or  of  the  nerves  that  subserve  the  sensations  of  coolness 
and  warmth.  It  is  true  that  when  the  skin  is  lightly  touched  in 
the  region  of  a  touch-spot  with  a  small  object  at  its  own  temperature 
the  sensation  is  one  of  pure  touch.  As  the  pressure  is  increased,  a 
sensation  of  pressure,  quite  distinct  from  that  of  contact,  may  be 
felt ;  and  if  the  pressure  is  still  further  increased,  a  sensation  of  pain 
may  be  elicited.  It  seems  to  be  quite  clearly  made  out  that  the 
pressure  sensation  in  this  case  is  due  not  to  excessive  stimulation 
of  the  touch-nerves,  but  to  stimulation  of  the  specific  pressure- 
nerves  when  the  threshold  is  reached.  The  most  natural  explana- 
tion of  the  pain  sensation  is  that  it,  too,  is  due  to  excitation  of  the 
nervous  apparatus  for  pain.  Similarly  (as  was  stated  on  p.  1042), 
if  the  skin  is  raised  to  higher  and  higher  temperatures,  the  response 
is  at  first  a  pure  sensation  of  warmth,  increasing  in  intensity  without 
changing  its  quahty.  When  a  certain  temperature  (about  45°  C.) 
is  exceeded,  the  sensation  changes  to  '  hot,'  either  because  a  pain 
element  is  now  added  to  the  pure  thermal  sensation,  or  because  the 
cold  spots  are  now  stimulated  as  well  as  the  warm  spots,  and  mingle 
their  specific  response  (cold  sensation)  with  that  of  the  warm  spots. 
Further  increase  of  the  temperature  will  cause  distinct  pain,  the 
sensation  assuming  a  burning  character.  When  a  cold  spot  is 
tested  with  decreasing  temperatures,  an  analogous  series  of  sensa- 
tions is  run  through,  the  pure  sensation  of  coolness  eventually  giving 
place  to  cold,  intense  cold,  and  finally  pain.  Here,  also,  it  is  simplest 
to  assume  that  the  pain  sensation  is  caused  not  by  excessive  stimu- 
lation of  warm  or  cold  spots,  but  by  excitation  of  the  specific  pain- 
spots.  In  any  case,  there  is  no  doubt  that  afferent  '  pain  '  fibres 
exist  which  are  anatomically  distinct  from  tlie  fibres  of  tactile  and 


CUTANEOUS  AND  INTERNAL  SENSATIONS  1045 

of  temperature  sensations.  For  the  conducting  paths  in  the  spinal 
cord  are  not  the  same  for  tactile  and  for  painful  impressions.  And 
in  certain  cases  of  disease  sensibility  to  pain  may  be  lost,  while 
tactile  sensations  are  still  perceived ;  or,  on  the  other  hand,  pain  may 
be  felt  in  cases  where  tactile  sensibility  is  abolished.  Loss  of  tem- 
perature sensation,  however,  is  usually  accompanied  by  loss  of 
sensibility  to  pain.  When  a  nerve  is  compressed,  the-  si-nsibility 
of  the  tract  supplied  by  it  disappears  for  cold  sooner  than  for 
warmth. 

Pain  has  been  defined  as  '  the  prayer  of  a  nerve  for  pure  blood.'  The 
idea  is  not  only  true  a.s  poetry,  but,  with  certain  deductions  and  limita- 
tions, true  as  physiolog^^;  that  is  to  say,  pain,  as  a  rule,  is  a  sign 
that  something  has  gone  wrong  with  the  bodily  machinery';  freedom 
from  pain  is  the  normal  state  of  the  healthy  body.  Physiologically, 
pain  acts  as  a  danger-signal.  It  points  out  the  seat  of  the  mischief, 
and  even,  in  certain  cases,  by  compelling  rest,  favours  the  process  of 
repair.  Thus,  the  surgeon  has  sometimes  looked  upon  pain  as  '  Nature's 
splint.'  But,  as  a  matter  of  fact,  a  certain  amount  of  pain  occurring 
at  intervals  is  not  incompatible  with  high  health;  and  probably  nobody, 
even  when  accidents  and  indiscretions  of  all  kinds  arc  avoided,  is  en- 
tirely free  from  pain  for  any  considerable  time.  Sometimes,  indeed, 
the  mere  fixing  of  the  attention  on  a  particular  part  of  the  body  is 
sufficient  to  bring  out  or  to  detect  a  slight  sensation  of  pain  in  it ;  and 
it  is  matter  of  common  experience  that  a  dull  continuous  pain,  like  that 
of  some  forms  of  toothache,  is  aggravated  by  thinking  of  it,  and  relieved 
when  the  attention  is  diverted. 

As  to  the  sensations  of  tickling  and  itching,  it  is  enough  to  say 
that  phj'siologists  are  not  agreed  whether  they  represent  specific 
sensibilities  subserved  by  special  nerves  distinct  from  those  of  touch 
and  pain,  or  merely  modifications  or  mixtures  of  these  sensations. 

Phenomena  observed  after  Section  of  Cutaneous  Nerves. — The 
innervation  of  the  skin  can  be  explored  not  only  by  appropriate 
stimulation  of  the  normal  skin,  but  by  study  of  the  defects  or  altera- 
tions of  sensibility  which  follow  section  of  a  cutaneous  nerve,  and 
which  may  be  observed  at  different  stages  in  its  regeneration.  In 
recent  years  this  has  proved  a  fruitful  method,  especially  in  experi- 
ments made  by  skilled  observers  in  whom  one  or  more  cutaneous 
nerves  were  intentionally  divided. 

A  very  elaborate  and  well-planned  investigation  has  been  made 
by  Trotter  and  Davies.  They  divided  at  different  times,  extending 
over  more  than  a  year,  no  fewer  than  seven  of  their  own  cutaneous 
nerves,  including  the  internal  saplu-nous  at  the  knee,  the  great 
auricular,  three  divisions  or  branches  of  the  internal  cutaneous  of 
the  arm  just  below  the  elbow,  and  a  branch  of  the  middle  cutaneous 
of  the  thigh.  The  operations  were  purposely  done  at  such  in- 
tervals as  would  allow  the  experience  gained  in  investigating  one 
area  to  be  applied  to  others.  About  a  quarter  of  an  inch  was  cut 
out  of  each  nerve,  and  the  ends  then  sutured  together.     '  In  each 


1046 


THE  SENSES 


case  the  area  of  skin  supplied  by  the  nerve  showed  defects  in  seven 
distinct  functions:  four  sensory — namely,  sensibihty  to  touch,  cold, 
heat,  pain — and  three  motor — namely,  vaso-motor,  pilo-motor, 
sudo-motor  (sweat-secretory).  The  sensory  changes  showed  a 
central  area  of  profound  loss,  an  area  of  moderate  extent  surrounding 


m/esrna'/>  TO  / 


STmifiNa  ouTLirVi 


Fig.  443. — Areas  of  Altered  Sensibility  produced  by  Section  of  all  Three  Branches 
of  the  Internal  Cutaneous  Nerve  of  the  Left  Forearm  (Trotter  and  Davies). 
(Reduced  by  Two-thirds.)  The  thick  lines  show  the  areas  of  anaesthesia  to  the 
brush.  The  thick  continuous  lines  enclose  the  areas  of  the  anterior  and  posterior 
branches.  The  thick  broken  line  and  heavy  shading  mark  the  area  of  the  in- 
crease in  anaesthesia  which  followed  section  of  the  middle  branch.  The  thin 
lines  show  the  areas  of  minimal  hypoaisthesia — i.e.,  the  'stroking  outline.'  The 
complete  oval  outline  is  the  '  stroking  outline  '  which  followed  section  of  the  pos- 
terior branch.  The  large  addition  to  the  oval  on  the  right  0/  the  diagram  shows  the 
increase  in  the  '  stroking  outline  '  which  followed  section  of  the  anterior  branch. 
The  thin  broken  line  and  fine  shading  show  the  additions  to  the  '  stroking  out- 
line '  produced  by  division  of  the  middle  branch. 

this  of  partial  loss,  and  a  large  area  in  which  a  qualitative  change 
could  be  alone  detected.'  The  maximal  extent  of  change,  and 
therefore  the  outer  boundary  of  this  third  area,  can  be  mapped  out 
by  getting  the  subject  to  determine  by  light,  stroking  touches  the 
area  which  feels  in  any  way  unnatural  when  he  touches  it  himself. 
The  most  common  feeling  is  that  the  skin  has  become  smoother  at 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


1047 


the  boundary  as  the  stroking  finger  crosses  it,  coming  from  the 
normal  skin.  This  area  is  ahvays  much  larger  than  the  area  in- 
cluded in  it,  in  which  by  quantitative  methods — e.g.,  the  use  of  a 
very  fine  camel's-hair  brush,  or  more  exactly  by  the  v.  Frey  hairs — 
the  sensibility  to  touch  can  be  shown  to  be  diminished  (region  of 
hypoaesthcsia  to  touch)  (Fig.  443)- 

For  a  variable  distance  within  the  '  stroking  outline  '  tin-  liypo- 


Fig.  444. — Middle  Cutaneous:  Left  Thigh  (Trotter  and  Davies)  (reduced  by  One- 
third  Linear).  Twenty-six  days  after  section.  Results  of  examination  with 
V.  Frey  hairs.  Toucli  r.pots  marked  •  responded  to  hair  of  280  milligrammes' 
pressure;  those  marked  o  to  hair  of  800  milligranunes;  and  those  marked  +  to 
hair  of  2,280  milligrammes.  The  continuous  line  marks  the  limit  within  which 
there  was  ana!Sthesia  to  the  camel's-hair  lirush. 

aesthesia  for  tactile  stimuli  is  so  slight  that  it  cannot  be  detected 
with  the  brush  or  with  cotton-wool,  or  even  with  the  v.  Frey  hairs. 
Like  those  of  normal  skin,  90  per  cent,  of  its  hair-bulbs  respond  to 
a  hair  exerting  a  pressure  of  70  milligrammes,  and  the  remaining 
10  per  cent,  to  hairs  exerting  a  pressure  of  140  or  280  milligrammes. 
Inside  this  zone  of  minimal  hypoa:sthesia  the  defect  of  sensibility 
rapidly  incr^'ases  as  we  pass  inwards,  each  line  of  hair  bulb  requiring 


r048 


THE  SENSES 


a  heavier  pressure  than  the  hne  external  to  it,  till  at  last  3^  or 
4  grammes'  pressure  is  needed  to  cause  a  sensation  of  touch,  and 
inside  of  this  line  of  hairs  the  skin  does  not  respond  at  all.  When 
a  bristle  of  this  pressure  fails  to  elicit  touch  sensation,  no  greater 
pressure  will  in  general  do  so  (Fig.  444). 

For  thermal  sensibihty  there  is  also  a  region  of  complete  anaes- 
thesia and  a  region  of  partial  anaesthesia.     The  best  way  of  out- 


••  ••  -         •    .•     •• 


•  •    •   .    ♦•     i'** 


•  • *  .  •      ^^ 

•  •  •  •  • 

*  •'  -  ...---V 


Fig-  445- — Middle  Cutaneous:  Left  Thigh  (Trotter  and  Davies).  Twenty-one  days 
after  section.  Results  of  examination  with  temperature  of  o°  C.  On  spots 
marked  •  stimulus  was  felt  as  cold;  on  spots  marked  o  it  was  felt  as  cool.  The 
blank  area  is  that  of  thermal  anaesthesia.  The  continuous  outline  marks  the 
limit  within  which  there  was  anaesthesia  to  the  camel's-hair  brush. 

lining  these  is  the  use  of  a  temperature  of  0°  C.  as  the  stimulus 
(Fig.  445). 

Outside  the  zone  of  complete  thermal  anaesthesia  there  is  a  region 
in  which  temperature  sensations  are  distinctly  elicited,  but  do  not 
possess  the  normal  intensity,  the  temperature  of  0°  C.,  for  example, 
being  felt  only  as  cool,  and  not  as  cold.  The  outer  limit  of  this 
region  is  the  line  at  which  the  temperature  of  0°  C-  is  first  felt  as 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


1049 


we  work  inwards  from  the  normal  skin  to  yield  the  sensation  of 
Gool  instead  of  cold.  Similarly,  the  outer  limit  of  thermo-hypo- 
aesthesia  can  be  determined  by  using  a  high  temperature  (50°  C). 
It  is  the  line  at  which  the  sensation  of  hot  yielded  by  the  normal 
skin  gives  place  to  the  sensation  of  warm.  The  two  Ix.undaries 
correspond  closely  when  allowance  is  made  for  the  separate  grouping 
of  cold  and  warmth  spots  on  the  normal  skin. 


Fig.  446. — Middle  Cutaneous  (External  Branch):  Left  Thigli  (Trotter  and  l>avirs>. 
Twenty-three  days  after  section.  Results  of  examination  with  algumeter  (ai> 
arrangement  by  which  a  needle  is  pressed  against  the  skin  by  a  hair  whose 
pressure  value  has  been  determined).  Spots  marked  •  reacted  by  sensation  ot 
pain  to  pressure  of  i,>S6o  milligrammes  (normal  threshold):  spots  marked  o  re- 
quired 2.280  milligrammes.  The  c<jntinuous  line  marks  the  area  within  which 
there  was  ana-sthesia  to  the  camel's-hair  brush. 


The  investigation  of  the  sensibility  of  the  skin  areas  for  painful 
stimuli  is  complicated  by  the  fact  that  during  a  certain  period, 
from  about  the  second  to  the  sixth  week  after  division  of  the  nerve, 
hyperalgesia  (increased  sensitiveness  to  painful  impn-ssions)  may 
appear.  This,  however,  does  not  seem  to  be  a  consequence  of  any 
sensory  loss,  but  rather  a  complication  due  to  an  irritative  change. 
When  this  is  taken  account  of,  it  is  found  that  the  defect  of  sensi- 
bility to  pain  after  nerve  section  rescmbk>s  the  defects  of   sensi- 


lOSO  THE  SENSES 

bility  to  touch  and  temperature,  showing  a  central  area  of  absolute 
anaesthesia  surrounded  by  a  zone  of  partial  loss,  which  is  slight 
towards  the  outer  boundary,  but  increases  as  we  pass  inwards 
(Fig.  446). 

After  section  of  a  nerve  function  is  recovered  only  as  a  result  of 
regeneration.  This  is  true  of  all  the  sensory  functions  of  the  skin 
and  of  the  pilo-motor  and  sudo-motor  functions.  Vaso-motor  tone 
in  the  affected  area  is  restored  much  sooner  than  the  other  functions. 
Tliis  rapid  recovery  probably  depends  upon  a  local  compensatory 
mechanism,  and  not  upon  regeneration  of  the  vaso-motor  fibres. 
Recovery  of  all  the  functions  dependent  upon  regeneration  begins 
about  the  same  time,  and  this  recovery  progresses  over  the  area  at 
about  the  same  rate  for  all,  although  the  rate  at  which  they  progress 
towards  normal  acuity  is  different. 

Sensibility  to  touch  probably  appears  a  little  earher  than  sensi- 
bility to  cold  and  pain.  Yet  the  recovery  of  touch  does  not  progress 
so  fast,  and  for  awhile  a  given  zone  of  the  recovering  area  remains 
hypoaesthetic  (less  sensitive  than  normal)  to  touch,  while  to  cold 
and  pain  it  soon  becomes  even  hypersensitive.  The  most  remark- 
able peculiarities  of  a  recovering  area  are  :  (i)  This  qualitative 
change,  in  virtue  of  which  cold,  pain,  and  the  pain  element  of  heat 
are  intensified,  while  touch  is  little  altered,  although  more  difficult 
to  elicit ;  (2)  the  reference  of  sensations,  not  to  the  point  stimulated, 
but  to  distant  parts  of  the  area. 

'When  a  spot  which  has  developed  this  peripheral  reference  is 
touched,  one  of  two  possibilities  may  occur:  either  the  touch  is 
felt  locally,  and  is  referred  as  well,  or  nothing  is  felt  locally,  and 
the  touch  is  felt  in  the  area  of  peripheral  reference.  The  region 
in  which  the  referred  touch  is  felt  is  always  at  the  edge  of  the  most 
peripheral  part  of  the  anaesthesia,'  perhaps  more  than  a  foot  away 
from  the  spot  actually  touched.  The  peripheral  reference  of  cold 
is  even  more  striking,  particularly  in  the  remarkable  intensity  of 
the  referred  sensation. 

Peripheral  reference  occurs  also  with  pain.  '  The  referred  pam 
shows  three  well-marked  qualities:  it  is,  proportionately  to  the 
stimulus,  very  intense  ;  it  does  not  reproduce  a  normal  sensation 
with  the  exactitude  found  in  the  case  of  touch  or  cold,  but  has  a 
special  quality  of  strangeness  and  unpleasantness,  such  as  no  pin- 
prick on  normal  skin  can  give;  finally,  it  produces  an  almost  irre- 
sistible desire  on  the  part  of  the  subject  to  rub  or  scratch  the  region 
in  which  it  is  felt.'  As  recovery  proceeds  the  local  sensory  response 
becomes  more  distinct,  and  the  abnormal  qualit}^  of  both  local  and 
referred  sensations  fades.  But  '  while  peripheral  reference  is  the 
earliest  phenomenon  of  recovery,  it  persists  until  recovery  is  so  far 
advanced  that  hypoaesthesia  is  scarcely  detectable  by  any  quanti- 
tative methods.' 


CUTANEOUS  AND  INTERNAL  SENSATIONS  1051 

It  is  a  remarkable  circumstance  that  during  regeneration  stimu- 
la  ion  of  the  n  rv  >trunk  itself  below  the  section,  by  the  application 
of  touch,  cold,  or  pain  stimuli  to  the  skin  over  its  course,  produces 
peripherally  referred  sensations  of  the  corresponding  kind.  This 
is  the  case  even  whenthe  nerve  is  stimulated  outside  the  formerly 
anaesthetic  area,  and  suggests  that  the  nerve-trunk  itself  has  ac- 
quired the  specific  sensibility  normally  associated  with  the  terminal 
organs  of  its  afferent  fibres  through  the  lowering  of  the  threshold 
for  the  fibres  themselves. 

The  work  of  Head,  who  was  the  pioneer  in  this  metliod  of  investiga- 
tion, must  also  be  mentioned.     He  found  that  when  the  median  nerve 
was  divided  in  his  own  arm,  total  loss  of  sensation  was  caused  over  the 
greater  part  of  the  index  and  miiidle  fingers,  and  over  a  portion  of  the 
thumb  in  its  palmar  aspect.     In  addition,  sensation  was  partially  lost 
over  a  larger  area,  where  there  was  complete  insensibility  to  certain 
stimuli,  such  as  light  touch,  moderate  heat  and  cold,  and  where  the 
contact  of  the  two  points  of  a  pair  of  compasses  could  not  be  discrimin- 
ated.    Recovery'  of  sensation  after  complete  division  of  a  peripheral 
nerve  began  with  the  restoration  of  sensibility  to  pain  and  to  extreme 
degrees  of  heat  and  cold ;  but  the  hand  still  remained  for  a  time  as 
insensitive   as   before  to   such  stimuli  as  slight  touch.     In  the  parts 
which  had  regained  their  sensibility  to  severe  stimuli,  like  pricking  and 
extremes  of  heat  and  cold,  the  sensation  radiated  widely,  was  referred 
to  remote  parts,  and  could  not  be  accurately  localized.     This  form  of 
sensibility  Head  calls  protopathic.     As  the  nerve  recovered  further,  a 
second  form  of  sensibility  appeared,  associated  with  accurate  localiza- 
tion of  cutaneous  stimuli  and  discrimination  of  two  compass  points. 
Light  touch  and   moderate  degrees  of  heat  and  cold  could  now  be 
again  appreciated.     This  form  of  sensibility  he  terms  epicritic.     A  third 
form  of  sensibility   [deep  sensibility)  was  investigated  after  complete 
division  of  the  radial  and  external  cutaneous  nerves  at  the  ellx)w. 
The  radial  half  of  the  arm  and  back  of  the  hand  became  totallj-  insensi- 
tive to  cutaneous  stimuli,   but  retained  their  sensibility  to    pressure 
or  to  any  stimulus  which  deformed  the  subcutaneous  structures,  as 
well  as  their  power  of  localization  of  such  stimuli.     The  alTerent  fibres 
upon  which  this  deep  sensibility  depends  must  run  with  the  motor 
nerves.     According  to  Head,  the  other  two  forms  of  sensibility  (proto- 
pathic and  epicritic)  also  depend  on  two  separate  systems  of  nerves. 
It  is  assumed  that  the  protopathic  fibres  regenerate  more  easily  and 
speedily  than  the  epicritic  or  than   the  motor  nerves  of   voluntary 
muscle.     The  protopathic  fibres  are  supposed  by  Head  to  exert  a  trophic 
influence.     A  part  deprived  of  its  nerve-supply  is  liable  to  injuries,  and 
the  sores  so  produced   heal  slowly.     But  as  soon  as   '  protopathic  ' 
sensibility  returns  to  the  part,  they  heal  rapidly,  even  in  the  absence 
of   all  epicritic   sensation.     The   intestine   is   described    as    j)Ossessing 
'  protopathic,'  but  not  '  epicritic,'  sensibility — i.e.,  it  reacts  to  extremes 
of  heat  and  cold,  but  not  to  moderate  heat  and  cold  or  light  touch. 

Head's  experimental  results  must  be  sliarply  distinguished  from  his 
interpretation  of  them,  and  the  student  is  warned  that  the  distinction 
of  protopathic  and  epicritic  scnsil)iiity  has  met  with  adverse  criticism. 
There  docs  not  seem  to  be  any  real  necessity  in  the  observed  facts  for 
introducing  so  revolutionary  a  conception  of  the  nervous  svstem. 
Nor  is  it  possible  to  uphold  tlie  distinction  in  any  thoroughgoing  fashion 
for  ail  structures.     For  instance,   in  abdominal  oix-nitions  jH-rformcd 


I052  THE  SENSES 

under  local  anaesthesia  it  has  been  seen  that  the  parietal  peritoneum 
is  quite  insensitive  to  touch,  pressure,  and  temperature  stimuli,  in- 
cluding extreme  temperatures  (Ramstrom),  while  pain  is  caused  by 
traction  on  it.  Its  sensibility  is  therefore  neither  purely  epicritic  nor 
purely  protopathic  in  Head's  sense.  In  like  manner  the  mucous  mem- 
brane of  the  mouth,  in  which  sensibility  only  to  touch  and  temperature 
is  present,  conforms  entirely  to  neither  type.  Its  sensibility  is  not 
alone  epicritic,  since  it  responds  to  extreme  temperatures,  nor  is  it 
purely  protopathic,  since  a  pin-prick  produces  no  painful  sensation. 

Localization  of  Cutaneous  Sensations. — We  not  only  perceive  the 
qualitjf  and  estimate  the  intensity  of  sensations  of  touch,  temperature, 
pain,  etc.,  but  are  able,  more  or  less  accurately,  to  localize  the  part  of 
the  body  from  which  the  sensorj'  impressions  come.  In  other  words, 
two  impressions  from  different  parts  of  the  body,  although  identical 
in  quality  and  intensity,  are  nevertheless  stamped  with  a  distinctive 
something,  which  may  be  called  the  local  sign.  This  power  of  localiza- 
tion is  not  equal  for  all  portions  of  the  body  nor  for  all  kinds  of  sensa- 
tions. It  is  best  developed  for  touch  (in  the  restricted  sense),  and  all 
the  varieties  of  common  sensation  are  better  localized  on  the  skin  than 
in  any  of  the  deeper  structures.  Tke  precise  mechanism  of  the  localiza- 
tion is  unknown.  But  we  must  suppose  that  each  peripheral  area  is 
'  represented  '  in  the  brain,  so  that  the  arrival  of  afferent  impulses  from 
it  affects  particularly  the  related  cerebral  area.  The  brain,  therefore, 
so  ix)  speak,  associates  excitation  of  a  given  cerebral  area  with  stimula- 
tion of  the  corresponding  peripheral  area,  and  thus  n«t  only  recognizes 
the  quality  and  quantity  of  the  resultant  sensation,  but  also  localizes 
it;  just  as  a  'waiter  who  watches  the  bell-indicator  not  only  learns  how 
a  bell  has  been  rung,  whether  once  or  twice,  peremptorily  or  languidly, 
but  also  in  which  room  it  has  been  rung.  If,  to  pursue  the  illustration 
a  little  farther,  he  is  aware  that  two  rooms  are  connected  with  one 
bell,  but  that  one  of  the  rooms  is  scarcely  ever  occupied,  he  associates 
the  ringing  of  the  bell  with  a  summons  from  the  other  room  even  when 
it  happens  to  be  rung  from  the  usually  vaeant  room.  In  like  manner 
the  brain  seems  to  connect  the  awrival  of  sensory  impulses  from  the 
internal  organs,  which  have  few  sensory  fibres,  and  these  perhaps  not 
often  stimulated,  with  excitation  in  a  related  cutaneous  region,  from 
which  it  is  constantly  receiving  sensory  impressions.  The  fact  already 
mentioned  (p.  863),  that  in  disease  of  internal  organs  the  pain  is  re- 
ferred to  some  portion  of  the  skin,  may  be  thus  explained. 

It  is  through  the  localization  of  touch  sensations  that  the  size  and 
form  of  objects  in  contact  with  the  skin  are  perceived  in  the  absence 
of  other  than  the  cutaneous  sensations,  and  especially  in  the  absence 
of  visual  and  muscular  sensations  (stereognosis). 

Muscular  Sensations  (Muscular  Sense),  etc. — Sometimes,  although 
rather  loosely,  grouped  together  as  muscular  sensations,  are  a  number 
of  forms  of  sensation  of  which  our  knowledge  is  much  less  accurate 
than  it  is  in  the  case  of  the  fundamental  skin  sensations.  Among 
these  may  be  mentioned  especially  (i)  the  sensations  by  which  the 
position  in  space  of  the  body  as  a  whole  or  of  particular  parts  is  recog- 
nized in  the  absence  of  visual  sensations;  (2)  the  sensations  associated 
with  movements,  passive  as  well  as  active;  (3)  the  sensations  associated 
with  resistance  to  movement.  In  none  of  these  groups  are  we  dealing 
with  purely  muscular  sensations;  cutaneous  tactile  sensations  and 
pressure  sensations  elicited  from  other  structures  than  muscles  are 
also  involved. 

Voluntary  muscular  movements  are  accompanied  with  a  peculiar 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


1053 


that  the 


sensation  of  effort,  graduated  according  to  the  strength  of  the  con- 
traction, and  affording  data  from  which  a  judgment  as  to  its  amount 
and  direction  may  be  formed. 

Some  writers  have  supix>sed  that  this  so-called  muscular  sense  does 
not  depend  upon  afferent  impulses  at  all,  hut  that  the  nervous  centres 
from  vvhicli  the  vohmtary  impulses  depart  take  tognizance,  retain  a 
record,  so  to  speak,  of  the  (juantlty  of  outgoing  nervous  force: 
effort  which  we  feel  in  lifting  a  heavy 
weight  is  an  effort  of  the  cells  of  the 
motor  centres  from  which  the  groups  of 
muscles  arc  inncr^'ated,  and  not  of  the 
muscles  themselves. 

But  although  this  feeling  of  central 
effort  or  outflow  (we  can  hardly  say  of 
central  fatigue)  may  be  a  factor,  it  cannot 
be  doubted  that  the  brain  is  kept  in  touch 
with  the  contracting  muscle  Ijy  impulses 
of  various  kinds  which  reach  it  by  diHerent 
afferent  cliannels. 

The  corpuscles  of  Pacini,  which  exist 
in  considerable  numbers  in  the  neigh- 
bourhood of  joints  and  ligaments,  and  in  the  periosteum  of  bones, 
would  seem  well  fitted  to  play  the  part  of  end-organs  for  the  tactile 
sensations  caused  by  the  movements  of  flexion,  extension,  or  rotation 
of  one  bone  on  another,  which  form  so  large  a  portion  of  all  voluntary 
muscular  movements.  And  it  has  been  stated  that  paralysis  of  these 
bodies  in  the  limbs  of  a  cat  by  section  of  the  nerves  going  to  them 
causes  a  characteristic  uncertainty  of  mo\cment  which  suggests  that 
something  necessary  to  normal  co-ordination  has  been  taken  away. 
Tendons  also  possess  afferent  nerve-fibres,  which  terminate  by  breaking 


Fig.  447.  —  Nerve  •  Ending  in 
Tendon  near  the  Insertion  of 
the  M\iscular  Fibres  (Golgi). 


Fig 


m.H.ff 


4,|8. — Muscle  Spindle  (after  Ruffini).  c.  sheath  of  the  spindle  :  n.tr..  trunk 
of  nerve,  which  sends  filircs  thnjiigh  the  sheath  into  the  spindle,  where  they 
form  endings  (pr.e.,  s.e.,  pl.f.)  of  various  kinds;  tn.u.b..  bundle  of  motor  fibres. 


up  into  reticulated  end-plates  (Fig.  447).  We  have  already  seen  that 
the  skeletal  muscles  possess  numerous  afferent  fibres  (p.  910).  Some 
of  these  must  be  nerves  of  ordinary'  sen.sation.  For.  altliough  when  a 
muscle  is  laid  bare  in  man  and  stimulated  electrically,  the  sensation 
does  not  in  general  amount  to  actual  pain,  it  is  capable,  under  the 
influence  of  strong  stimuli,  of  taking  on  a  painful  character.  And 
nobody  who  has  felt  the  severe  and  sometimes  almost  intolerable  pain 
of  muscular  cramp  would  be  likely  to  deny  the  existence  of  sensor>' 
muscular  nerves.  But  after  deducting  these,  we  must  assume  that  a 
large  proportion  of  the  afferent  nerves  of  muscle  have  other  functions, 
and  among  them  may  be  the  conveyance  of  impulses  connected  with 


1054  ^^^  SENSES 

the  muscular  sense.  The  muscle-spindles  or  neuro-muscular  spindles 
(Fig.  448),  peculiar  structures  which  occur  in  large  number  in  most 
of  the  skeletal  muscles,  and  have  been  carefully  studied  by  Huber, 
Sihler,  Ruffini,  and  other  observers,  are  the  terminations  of  many  of 
the  sensory  fibres.  They  are  long  narrow  bodies,  with  a  thick  sheath 
of  connective  tissue  enclosing  fine  striped  muscular  fibres.  Medul- 
lated  nerve-fibres  enter  the  spindle,  and  there,  dividing  into  branches 
and  losing  their  medullary  sheath,  form  endings  of  various  kinds  around 
and  between  the  muscular  fibres.  It  is  possible  that  in  contraction 
of  the  muscles  the  nerve-fibres  in  the  spindles  are  compressed,  and  thus 
mechanically  stimulated. 

In  the  spinal  cord  these  impulses  are  conducted  up  through  the 
posterior  column;  and,  although  less  is  known  as  to  the  paths  they 
follow  in  the  higher  parts  of  the  central  nervous  system,  it  is  certain 
that  there  is  some  afferent  bond  of  connection  between  the  cortical 
motor  areas  and  the  muscles  which  they  control  (p.  929). 

Tactile  sensations  set  up  in  the  skin  or  mucous  membrane  lying 
over  contracting  muscles  may  also  help  the  nervous  motor  mechanism 
in  appreciating  and  regulating  the  amount  of  contraction ;  but  the  fact 
that,  in  anaesthesia  of  the  mucous  membrane  covering  the  vocal  cords 
produced  by  cocaine,  the  voice  is  not  at  all  impaired,  shows  that  mus- 
cular contractions  of  extreme  nicety  can  be  carried  on  without  any 
such  aid. 

Sensations  of  Hunger  and  Thirst. — These  are  representatives  of 
the  group  of  interior  sensations.  As  Tiedemann  pointed  out  long 
ago,  at  least  two  elements  are  involved  in  the  somewhat  vague 
sensation  of  hunger :  the  local  sensation  of  emptiness  in  the  stomach, 
and  the  general  sensations  of  malaise,  depression,  and  weakness. 
There  is  some  evidence  that  the  general  sensations  are — in  part  at, 
least — dependent  upon  the  state  of  the  stomach.  But  it  would 
appear  that — at  any  rate,  during  prolonged  deprivation  of  food — a 
general  condition  of  the  tissues  may  exist  which  can  arouse  in  con- 
sciousness the  sensation  of  hunger,  even  after  the  stomach  has  been 
amply  filled.  Thus  a  patient  with  a  fistula  in  the  upper  part  of 
the  small  intestine  constantly  suffered  from  hunger  in  spite  of  the 
enormous  quantities  of  food  consumed.  The  stomach  always  felt 
full,  but  as  most  of  the  food  escaped  from  the  fistula,  the  tissues 
continued  to  be  starved,  and  the  general  sensation  of  hunger  re- 
mained (Hertz).  In  diabetes  the  same  thing  may  be  observed. 
On  the  other  hand,  it  was  noted  by  Carlson  and  one  of  his  pupils 
that  after  a  fast  of  five  days  practically  all  of  the  mental  depression 
and  some  of  the  feeling  of  weakness  disappeared  during  the  first 
meal.  He  therefore  concluded  that  the  depression  of  the  central 
nervous  system  was  essentially  a  reflex  condition,  depending  prob- 
ably on  afferent  impulses  from  the  digestive  tract,  rather  than  a 
result  of  deficiency  of  nutrient  material  in  the  blood.  Complete 
recovery  from  the  bodily  weakness,  however,  did  not  take  place 
till  the  second  or  third  day  after  breaking  the  fast. 

An   important   factor   in   the   local   sensations   associated   with 
hunger  is  the  strong  periodical  contractions  of  the  empty  stomach. 


CUTANEOUS  AND  INTERNAL  SENSATIONS 


1055 


which  have  been  shown  to  coincide  with  tlie  liuiigcr  pains  (Cannon 
and  Washburn). 

Car]sf)n  was  able  in  observations  on  a  man  witli  a  permanent 
gastric  listula  to  confirm  tiiis  coincidence.     Even  when  the  empty 


■MMiliiJMa^^ 


Fig.  449. — Commencement  of  Gastric  Hunger  Contractions  (the  Large  Elevations) 
in  a  Man.  At  x  the  belt  was  tightened  and  the  hunger  contractions  inhibited. 
To  be  read  from  left  to  right  (Carlson  and  Lewis). 

stomach  was  artificially  caused  to  contract  by  distending  it  witli  a 
balloon,  the  man  experienced  a  typical  hunger  pain.  During  his 
own  five  days'  fast  Carlson  recorded  these  contractions  by  means 


Fig.   450.— Gastric  Hunger  Contractions  in  a  M.m  at  a  More  A'h  .inccd  .n;     1  ^ 

Stage  than  in  Fig.  449.  Tightoniiig  of  the  Iult  at  x  did  not  stop  tlic  r<in. 
tractions,  which  ran  the  usual  course  to  their  termination.  To  be  read  from 
left  to  right  (Carlson  and  Lewis). 

of  a  small  balloon  attached  to  a  rubber  tube,  which  was  swallowed 
and  allowed  to  remain  in  the  stomach.  Tlie  lube  was  connected 
to  a  recording  apparatus.  It  was  foimd  possible  to  go  to  sleep 
with  the  balloon  in  the  stomach,  and  to  obtain  a  record  all  through 


1056  THE  SENSES 

the  night.  After  the  first  day  of  starvation  the  hunger  sensation 
referred  to  the  epigastrium  was  almost  continuous,  and  did  not 
wholly  disappear  during  the  intervals  between  the  periods  of 
vigorous  gastric  contractions.  This  feeble  continuous  hunger  sen- 
sation was  obviously  associated  with  the  increased  tonus  and  the 
more  or  less  continuous,  although  weak,  rhythmical  contractions 
that  correspond  to  the  periods  of  relative  quiescence  of  the  empty 
stomach  during  prolonged  starvation.  The  precise  manner  in  which 
the  hunger  contractions  of  the  stomach  arouse  the  pangs  or  pains 
of  hunger  remains  in  doubt.  Since  the  sensation  has  a  specific 
character,  it  is  to  be  supposed  that  it  is  subserved  by  a  special 
sensory  apparatus  with  receptors  in  the  stomach.  The  vagi  do  not 
seem  to  be  concerned.  But  the  gastric  contractions  during  digestion  of 
a  meal  notoriously  do  not  cause  such  sensations,  and  therefore  it  has 
been  suggested  that  the  nervous  mechanism  associated  with  the 
local  sensation  of  hunger  becomes  more  and  more  excitable  in  the 
absence  of  food,  until  at  last  the  threshold  is  reached  at  which  the 
stimulus  connected  with  the  hunger  contractions  becomes  effective. 
It  comes  to  the  same  thing  to  say  that  the  presence  of  food  in  some 
way  inhibits  the  discharge  which  leads  to  the  sensation.  This, 
however,  is  only  another  way  of  saying  that  the  true  explanation  is 
still  to  seek. 

Carlson  was  unable  to  confirm  the  common  statement  that 
hunger  disappears  after  the  third  day  of  starvation,  although  there 
was  certainly  some  decrease  in  the  sensation  of  hunger,  and  especi- 
ally in  appetite,  on  the  fourth  and  fifth  days.  As  has  been  often 
shown,  the  deprivation  of  food  for  long  periods,  or  even  till  death, 
when  water  is  allowed,  is  not  associated  with  acute  suffering. 

Appetite  is  distinguished  from  hunger  by  those  observers  who 
have  studied  the  question  most  precisely,  but  of  the  physiological 
basis  of  the  sensations  that  constitute  appetite  we  know  even  less 
than  we  do  of  the  physiological  basis  of  hunger.  The  taking  of 
food  blunts  the  appetite,  as  it  stills  hunger.  Fasting  evokes  both. 
Yet  during  a  prolonged  fast,  appetite,  the  desire  for  food  and  the 
pleasure  in  the  thought  or  at  the  sight  of  it,  may  disappear,  or  be 
much  lessened,  while  the  hunger  pangs  are  still  sharp.  The  smell 
and  taste  of  agreeable  food  and  the  mental  representations  of  these 
sensations  are  elements  in  appetite,  and  even  the  associations  con- 
nected with  the  time  and  place  of  a  customary  meal  and  with  those 
who  share  it.  But  there  is  a  gastric  element  as  well:  the  mere 
filling  of  the  stomach  apart  from  the  passage  of  nutrient  material 
into  the  blood  helps  to  satisfy  the  appetite;  the  emptying  of  the 
stomach  in  the  course  of  digestion  seems  of  itself  to  take  a  part  in 
restoring  the  appetite  for  the  next  meal.  To  what  extent,  if  at  all, 
the  gastric  element  in  the  sensation  of  appetite  is  dependent  upon 
the  same  mechanism  as  the  gastric  element  in  hunger  is  unknown. 


CUTANEOUS  AND  ISlhkNAL  >,LS^AlluNS  1037 

Some  have  supposed  that  the  same  stimulation  which,  when  its 
intensity  is  sufficiently  increased,  causes  gastric  hunger  pains, 
causes  in  smaller  intensity  a  milder  hunger  sensation,  which  is  the 
gastric  factor  in  appetite.  The  vagi  do  not  seem  to  contain  fibres 
concerned  in  the  sensations  of  hunger  or  appetite.  After  section 
of  these  nerves,  dogs,  when  they  survive  some  time,  eat  ravenously, 
although  the  food  is  often  regurgitated  (p.  396). 

Thirst. — This  is  a  sensation,  referred  chiefly  to  the  pharynx  and 
certain  of  the  sensory  nerve  fibres  of  this  region,  supplied  by  the 
glosso-pharyngeal  nerve,  may  be  assumed  to  be  specificallv  related 
to  it.  Under  ordinary  conditions  the  sensation  is  elicited  through 
the  afferent  nerves  of  the  pharynx  when  the  mucous  membrane 
becomes  dry,  as  when  dry  c-r  salt  food  is  eaten,  or  dry  and  dusty 
air  inhaled,  and  local  moistening  of  the  area  in  question  gives 
temporary  relief,  even  when  no  water  is  swallowed.  When  water 
is  long  withheld,  the  water-content  of  all  the  tissues  sinks,  and  a 
more  intense  and  distressing  thirst,  which  cannot  be  allayed  in  any 
way  except  by  the  ingestion  of  water,  ensues.  Probably  in  this 
case  afferent  impulses  originating  in  many  organs,  and  conditioned 
in  some  way  by  the  abnormally  low  water-content  of  the  blood  and 
tissues,  as  well  as  a  more  direct  action  of  the  loss  of  water  upon  the 
(unknown)  centre  in  which  the  sensation  is  represented,  are  re- 
sponsible. 

Relation  of  Stimulus  to  Sensation. — It  is  impossible  to  measure 
sensation  in  terms  of  stimulus.  All  that  we  can  do  is  to  compare 
differences  in  the  intensity  of  stimuli  and  differences  in  the  resultant 
sen.sations,  or,  in  other  words,  to  compare  stimuli  together  and  to  com- 
pare sensations  together.  And  when  we  determine  the  amount  by 
which  a  given  stimulus  must  be  increased  or  diminished  in  order  that 
there  may  be  a  just  perceptible  increase  or  diminution  in  the  sensation, 
it  is  found  that  (with  certain  limitations)  the  two  are  connected  by  a 
simple  law:  Whatever  the  absolute  strength  of  a  stimulus  of  given  kind 
may  be,  it  must  be  increased  by  the  same  fraction  of  its  amount  in  order 
that  a  difference  in  the  sensation  may  be  perceived  (sometimes  calle<i 
Weber's  law).  Thus,  a  light  of  the  strength  of  one  standard  candle 
must  be  increased  by  fi^th  candle,  a  light  of  10  candles  by  i\J*o,  and  a 
light  of  100  candles  by  a  candle,  in  order  that  the  eye  may  perceive 
that  an  increase  has  taken  place,  just  as  the  weight  nccessarj'  to  turn 
a  balance  increases  with  the  amount  already  in  the  pans.  The  fraction 
varies  for  the  different  senses.  It  is  about  ,Jf,  for  light,  \  for  sound. 
But  it  would  appear  that  Weber's  law  dues  not  hold  for  the  pressure 
sense,  nor  for  the  other  senses  above  and  below  certain  limits.  Fcchncr, 
making  various  assumptions,  has  thrown  Weber's  law  into  the  form 

y=fi  ^3^    where  y  is  the  intensity  of  sensation,  x  the  intensity  of 

stimulation,  Xq  the  smallest  intensity  of  stimulus  which  can  be  jxrceivcd 
(liminal  intensity),  and  k,  a  constant.  This  so-called  psycho-physical 
law  of  Fechner  states  that  the  sensation  varies  as  the  logarithm  of  the 
stimulus.  But  Fechner's  law  has  been  subjected  to  serious  criticism, 
and  the  subject  cannot  be  further  pursued  here. 

67 


1058  THE  SENSES 

PRACTICAL  EXERCISES  ON  CHAPTER  XVIII. 
VISION. 

I.  Dissection  of  the  Eye. — The  student  may  profitably  refresh  his 
memory-  on  the  anatom}'  of  the  eye  by  dissecting  a  fresh  eye — that  of 
a  large  animal  like  an  ox  is  preferable,  but  the  eye  of  a  sheep  or  dog 
may  also  be  used.  The  eye  is  removed  from  the  orbit  by  cutting 
through  the  conjunctiva  where  it  is  reflected  on  to  the  eyelids,  care- 
fully severing  the  extrinsic  muscles  and  scooping  the  eyeball  out  of  the 
mass  of  loose  connective  tissue  and  fat  in  which  it  is  embedded,  and 
which  serves  as  a  cushion  to  protect  it  from  injury  during  its  move- 
ments. Observe  the  transparent  cornea  in  front,  blending  at  its  pos- 
terior border  with  the  opaque  sclerotic,  which  is  covered  by  a  layer  of 
conjunctiva  reflected  from  the  lids.  On  clearing  the  fat  cautiously 
away,  the  tendinous  insertions  of  the  external  or  extrinsic  muscles  of 
the  eyeball  into  the  anterior  part  of  the  sclerotic  will  be  seen.  Identify 
the  various  muscles  (p.  1023). 

Immerse  the  eye  in  water  in  a  small  glass  dish,  with  the  cornea 
uppermost.  The  interior  can  now  be  seen,  because  the  refractive 
index  of  the  cornea  being  nearly  the  same  as  that  of  water,  the  light  is 
only  very  slightly  refracted  there.  The  same  effect  is  produced  when 
a  cover-slip  is  placed  over  the  cornea  in  the  air;  a  plane  surface  being 
substituted  for  the  curved  anterior  surface  of  the  cornea,  its  refraction 
is  abolished.  Observe  in  the  fundus  of  the  eye  the  optic  disc,  eccentric- 
ally placed  in  the  retina,  and  the  retinal  vessels  radiating  out  from  it. 
A  portion  of  the  fundus  shows  brilliant  iridescent  colours  in  many 
animals  (the  tapetum  lucidum).  This  portion  is  abruptly  bounded  by 
a  line  a  little  above  the  optic  disc.  The  appearance  is  due  to  a  peculiar 
arrangement  of  the  connective-tissue  (including  elastic)  fibres  in  this 
part  of  the  choroid. 

Pinch  up  with  forceps  a  small  portion  of  the  sclerotic  a  little  posterior 
to  its  junction  with  the  cornea,  and  clip  it  away  with  fine,  blunt- 
pointed  scissors,  being  careful  not  to  penetrate  the  choroid  layer,  which 
lies  immediately  beneath  the  sclerotic.  Extend  the  incision  through 
the  sclerotic  backwards,  and  then  transversely,  and  peel  off  strips  of 
the  sclerotic  from  behind  forwards.  The  lower  surface  of  the  sclerotic 
(the  so-called  lamina  fusca)  is  dark,  owing  to  the  presence  in  it  of  the 
same  pigment  which  is  so  abundant  in  the  choroid  coat.  Go  on  re- 
moving the  sclerotic  piecemeal  until  a  considerable  area  of  the  dark 
choroid  layer  is  exposed  with  the  ciliary  nerves  passing  forward  on  its 
surface  towards  the  iris.  One  or  other  of  the  long  ciliary  arteries  may 
also  be  seen  coursing  between  the  sclerotic  and  choroid  if  the  sclerotic 
happens  to  have  been  removed  at  its  position.  On  the  anterior  part  of 
the  choroid  may  be  observed  some  pale  fibres  passing  backwards  from 
the  comeo-sclerotic  junction.  They  are  the  meridional  fibres  of  the 
ciliary  muscle  (p.  982). 

The  eye  being  immersed  in  water,  remove  cautiously  with  the  forceps 
and  scissors  the  portion  of  the  choroid  exposed.  The  retina  is  now  seen 
as  a  pale  membrane,  transparent  when  quite  fresh,  but  becoming  whitish 
soon  after  death.  Cut  through  sclerotic,  choroid,  and  retina  about  half- 
way round  the  eyeball,  a  little  posterior  to  the  corneo-sclerotic  junction. 
The  vitreous  humour  will  bulge  out.  Since  its  refractive  index  is 
nearly  th?  sa-me  as  that  of  water,  it  is  scarcely  observed  when  im- 
mersed, a  ul  the  interior  of  the  eye  can  be  easily  seen  through  it. 

The  optic  disc  can  now  be  again  studied,  with  the  stump  of  the  optic 


PRACTICAL  EXERCISES  lo'p 

nerve  entering  it  and  the  retinal  vessels  piercing  the  disc.  In  the 
centre  of  the  retina  is  the  yellow  spot. 

In  4:he  anterior  portion  of  the  evcball  note  the  crystalline  lens,  and 
at  its  circumference  the  radiating  lokls  of  the  choroid  called  the  cihar)' 
processes.  Closely  covering  the  ciliary  processes,  the  anterior  border 
of  the  retina  forms  the  era  serrata,  a  plaited  arrangement  like  an  old- 
time  ruff. 

Now  complete  the  separation  of  the  anterior  and  posterior  portions 
of  the  eyeball.  Remove  tlie  vitreous  Inimour.  noting  that  it  is  attached 
to  the  ciliary  processes  and  the  posterior  surfcice  of  the  capsule  of  the 
lens  by  its  enveloping  membrane,  the  hyaloid  membnine.  With 
scissors  snip  through  the  comco-sclerotic  junction  at  one  point  down 
to  the  border  of  the  lens,  and  observe  tlie  suspensory  ligament  passing 
from  the  ciliary  body  chiefly  towards  the  anterior  surface  of  the  lens, 
wliere  it  blends  with  the  lens  'ai^sule.  Open  the  anterior  chamber  of 
the  eye  by  an  incision  tlirougii  the  cornea  in  front  of  its  jun*  tion 
with  the  sclerotic.  It  is  filled  with  the  clear,  watery,  aqueous  humour. 
Note  the  pigmented  iris  projecting  in  front  of  the  lens. 

Remove  the  sclerotic  and  cornea  for  some  distance  along  their  line 
of  junction,  using  gentle  pressure  with  the  edge  of  a  fine  knife  to  separate 
the  junction  from  the  attached  border  of  the  iris.  The  ciliary  muscle, 
forming  a  pale,  narrow  ring  around  the  eye  at  the  corneo-sclerotic 
junction  will  be  thus  exposed.  Its  external  surface  is  closely  adherent 
to  the  sclerotic,  and  its  internal  blends  with  the  ciliary  body.  The 
circumference  of  the  iris  is  attached  at  its  anterior  border.  Posteriorly 
it  passes  into  the  choroid. 

Take  out  the  lens  and  observe  the  curvature  of  its  anterior  and 
posterior  surfaces.  Determine  which  has  the  greater  curvature.  In 
the  excised  eye  the  lens  will,  of  course,  be  in  the  condition  of  relaxed 
accommodation . 

2.  Formation  of  Inverted  Image  on  the  Retina. — Fix  the  eye  of  an  ox 
or  of  a  dog  or  rabbit,  after  careful  removal  of  part  of  the  posterior 
surface  of  the  sclerotic,  in  one  end  of  a  blackened  tube,  with  the  cornea 
in  front.  A  tube  made  by  rolling  up  a  piece  of  thick  brown  paper  will 
do.  Place  a  candle  in  front  of  the  eye.  Look  through  the  other  end 
of  the  tube,  and  observe  the  inverted  image  of  the  candle  formed  on 
the  retina.  Move  the  candle  until  the  image  is  as  sharp  as  possible. 
Now  bring  between  the  candle  and  the  eye  a  concave  lens.  The  image 
becomes  blurred,  the  candle  must  be  put  farther  away  to  render  it 
distinct,  and  perhaps  no  position  of  the  candle  can  be  found  which  will 
give  a  sharp  image.  If  the  lens  is  convex,  the  candle  must  be  brought 
nearer,  and  a  sharp  image  can  always  be  formed  by  bringing  it  near 
enough.  If  both  a  convex  and  a  concave  glass  be  placed  in  front  of 
the  eye,  they  will  partially  or  wholly  neutralize  each  other.  Instead 
of  the  candle  a  window  may  be  looked  at.  If  the  eye  of  an  albino 
rabbit  can  be  obtained,  it  is  not  necessary  to  remove  a  p>art  of  the 
sclerotic. 

3.  Helmholtz's  Phakoscope  (Fig.  451). — This  instrument  is  em- 
ployed in  studying  the  ciianges  that  take  place  in  the  curvature  of  the 
lens  during  accommodation.  It  is  to  be  used  in  a  dark  room.  A  candle 
is  placed  in  front  of  the  two  prisms  P,  P'.  The  observer  looks  through 
the  hole  B;  the  observed  eye  is  placed  at  a  hole  opposite  the  hole  A. 
The  candle  or  the  observed  eye  is  moved  till  the  observer  sees  three 
pairs  of  images,  one  pair,  the  brightest  of  all,  reflected  from  the  anterior 
surface  of  the  cornea;  another,  the  largest  of  the  three,  but  dim,  re- 
flected from  the  anterior  surface  of  the  lens;  and  a  third  pair,  the 
smallest  of  all,  reflected  from  the  posterior  surface  of  the  lens  (Fig.  402. 


io6o 


THE  SENSES 


Fig.  451. — Phakoscope. 


p.  981).  The  last  two  pairs  can,  of  course,  only  be  seen  within  the  pupil. 
The  observed  eye  is  now  focussed  first  for  a  distant  object  (it  is  enough 
that  the  person  should  simply  leave  his  eye  at  rest,  or  imagine*  he  is 
looking  far  away),  and  then  for  a  near  object  (an  ivory  pin  at  A). 
During  accommodation  for  a  near  object  no  change  takes  place  in  the 
size,  brightness,  or  position  of  the  first  or  third  pair  of  images;  there- 
fore the  cornea  and  the  posterior  surface  of  the  lens  are  not  altered. 
The  middle  images  become  smaller,  somewhat  brighter,  approach  each 
other,  and  also  come  nearer  to  the  corneal  images.  This  proves  [a)  that 
the  anterior  surface  of  the  lens  undergoes  a  change  ;  [b)  that  the 
change  is  increase  of  curvature  (diminution  of  the  radius  of  curvature), 
for  the  virtual  image  reflected  from  a  convex  mirror  is  smaller  the 
smaller  is  its  radius  of  curvature.      (The  third  pair  of  images  really 

undergo  a  slight  change,  such 
as  would  be  caused  by  a  small 
increase  in  the  curvature  of 
the  posterior  surface  of  the 
lens  ;  but  the  student  need 
not  attempt  to  make  this 
out.) 

4.  Scheiner's  Experiment. — 
Two  small  holes  are  pricked 
with  a  needle  in  a  card,  the 
distance  between  them  being 
less  than  the  diameter  of  the 
pupil.  The  card  is  nailed  on 
a  wooden  holder,  and  a  needle 
stuck  into  a  piece  of  wood  is  looked  at  with  one  eye  through  the  holes. 
When  the  eye  is  accommodated  for  the  needle,  it  appears  single ;  when 
it  is  accommodated  for  a  more  distant  object,  or  not  accommodated  at 
all,  the  needle  appears  double.  The  two  images  approach  each  other 
when  the  needle  is  moved  away  from  the  eye,  and  separate  out  from 
each  other  when  it  is  moved  towards  the  eye.  When  the  eye  is  ac- 
commodated for  a  point  nearer  than  the  needle,  the  image  is  also 
double;  the  images  approach  each  other  when  the  needle  is  brought 
closer  to  the  eye,  and  move  away  from  each  other  when  it  is  moved 
away  from  the  eye.  If  while  the  needle  is  in  focus  one  of  the  holes  be 
stopped  by  the  finger,  the  image  is  not  affected.  When  the  eye  is 
focussed  for  a  greater  distance  than  that  of  the  needle,  stopping  one 
of  the  holes  causes  the  image  on  the  other  side  of  the  field  of  vision 
to  disappear;  if  the  eye  is  focussed  for  a  smaller  distance,  the  image 
on  the  same  side  as  the  blocked  hole  disappears  (Fig.  452).  To  de- 
termine the  near-point  of  distinct  vision  (p.  989)  the  card  may  be 
mounted  vertically  on  a  cork,  and  this  fastened  by  a  rubber  band  to 
the  end  of  a  foot-rule.  Move  a  needle,  also  inserted  vertically  into  a 
cork,  along  the  rule,  beginning  at  the  end  farthest  from  the  eye,  until 
with  the  strongest  effort  of  accommodation  it  is  seen  double.  Then 
push  it  back  slightly  to  the  point  at  which,  again  with  maximum 
accommodation,  it  is  just  seen  single.  Repeat  the  measurement  with 
a  needle  mounted  horizontally.  If  regular  astigmatism  is  present, 
the  distances  will  not  be  the  same.  Most  eyes  have  slight  regular 
astigmatism. 

In  myopic  persons  the  far-point  of  distinct  vision  can  also  be  de- 
termined by  Scheiner's  experiment.  The  needle  being  left  on  a  shelf 
at  the  level  of  the  eye,  the  person  walks  away  from  it  backwards,  re- 
garding it  all  the  time  through  the  perforated  card,  till  it  is  no  longer 
seen  :. ingle. 


PRACTICAL  EXERCISES 


1061 


5.  Kuhne's  Artificial  Eye. — This  is  an  elongated  box  provided  with 
a  glass  Icvs  to  represent  the  cr>-stallinc.  and  a  ground-jjiass  iilatc  to 
represent  the  retina.  The  box  is  filled  witli  water  to  which  a  little 
eosin  has  been  added.  The  water  must  be  perfectly  clear.  If  the 
tap-water  is  turbid  it  should  be  filtered  or  allowed  to  settle,  or  dis- 
tdlcd  water  should  be  used.  A  beam  of  sunlight  or  electric  light,  or, 
in  case  these  are  not  available,  a  beam  from  an  oil  stereopticon,  is  made 
to  pass  through  the  box.  Many  of  the  facts  of  vision  can  be  illustrated 
by  means  of  this  piece  of  apparatus.  The  modification  of  it  introduced 
by  Lyon  is  very  convenient. 

(a)  Let  the  rays  of  light  pass  through  an  arrow-shaped  slit  in  a  piece 
of  cardboard.  An  inverted  image  of  the  arrow  is  formed  on  the  retina. 
Move  the  retina  nearer  to  or  farther  from  the  lens  to  make  the  image 
sharp.  In  the  eye  of  man  and  of  most  animals,  accommodation  is 
not  brought  about  by  a  cliange  in  the  distance  of  retina  and  lens,  but 
by  a  change  of  curvature  in  the  lens. 

(6)  Remove  the  lens.  Tlic  focus  is  now  far  behind  the  retina.  This 
illustrates  the  state  of  matters  after  the  lens  has  been  removed  for 
cataract.  The  arrow 
can  again  be  sharply 
focussed  on  the  retina 
by  putting  a  convex 
lens  in  front  of  the 
artificial  eye.  But 
this  must  be  much 
weaker  than  the  lens 
which  has  been  re- 
moved, for  if  the 
latter  be  placed  in 
front  of  the  eye,  the 
image  is  formed  a 
little  behind  the 
cornea. 

(c)  Replace  the  lens. 
Move  the  retina  so 
far  back  that  the 
image  is  focussed  in 
front  of  it.  This  is 
the  condition  in  the 
myopic  eye.  Put  a 
weak  concave  lens  in 
front  of  the  eye;  the  image  now  falls  more  nearly  on  the  retina.  Mo\c 
the  retina  forward  so  that  the  focus  is  behind  it.  This  corresponds 
to  the  hypermetropic  eye.  Put  a  weak  convex  lens  in  front  of  the 
eye  to  correct  the  defect. 

{d)  Observe  that  a  plate  with  a  hole  in  it,  placed  in  front  of  the  eye, 
renders  an  indistinctly  focussed  image  somewhat  sharjicr  by  cutting 
off  the  more  divergent  periplicral  rays. 

[e)  Fill  with  water  the  chamber  in  front  of  the  curved  glas.s  that  repre- 
sents the  cornea.  The  focus  is  now  behind  the  back  of  the  eye  alto- 
gether. Refraction  by  the  cornea  is  here  al)olished,  as  is  the  case  in 
vision  under  water.  An  additional  lens  inside  the  eye,  or  a  weaker 
one  in  front  of  it,  corrects  the  defect.  Fishes  have  a  much  more  nearly 
spherical  lens  than  land  animals,  and  a  Hat  cornea. 

(J)  Fill  the  hollow  cylindrical  lens  with  water,  and  place  it  in  front  of 
the  artificial  eye.  The  eye  is  now  astigmatic.  A  jx>int  of  light  is 
focussed  on  the  retina,  not  as  a  point,  but  as  a  line.     The  vertical  and 


Fig.  452. — Scheiner's  E.xperimont.  In  the  lower  figure 
the  eye  is  focussed  for  a  point  farther  away  than  the 
needle,  in  the  upper  for  a  nearer  point.  The  con- 
tinuous lines  represent  ra>"S  from  the  needle,  the  inter- 
rupted lines  rays  from  the  point  in  focus. 


io62 


THE  SENSES 


horizontal  limbs  of  a  cross  cut  out  of  a  piece  of  cardboard  and  placed 
in  the  path  of  the  beam  of  light  cannot  be  both  focussed  at  the  same 
time. 

6.  Astigmatism  (Regular). — (i)  Look  at  a  figure  showing  a  number 
of  lines  radiating  horizontally,  vertically,  and  in  intermediate  directions 
from  a  common  centre.  First  fix  the  figure  at  such  a  distance  that  one 
can  comfortably  accommodate.  If  astigmatism  is  present,  all  the  lines 
cannot  be  seen  with  equal  distinctness  at  the  same  time,  but  they  can 
u.  all  be  successively  accommodated  for. 

Next,  bring  the  figure  to  the  near- 
point  of  distinct  vision  for  the  hori- 
zontal and  neighbouring  lines.  Prob- 
ably the  vertical  lines  will  be  blurred 
and  cannot  be  made  as  distinct  as  the 
horizontal  by  any  effort  of  accom- 
modation. If  the  eye  is  distinctly 
astigmatic,  the  difference  will  be 
marked. 

(2)  Use  the  Ophthalmometer.  —  A 
con venient  form  is  shown  in  Figs.  453 
and  454. 

Raise  or  lower  the  chin-rest  till  the 
upper  bar  of  the  head-rest  is  just 
aiiove  the  patient's  eyebrows,  his  head 
being  exactly  vertical.  The  eye  not 
to  be  examined  is  covered  with  the 
blind.  The  patient  looks  steadily  into 
the  opening  of  the  tube  with  his  eye 
wide  open.  The  height  of  the  instru- 
ment having  been  adjusted,  a  clear 
image  of  the  mires  is  obtained  by 
focussing.  The  tube  is  then  turned 
horizontally  slightly  to  right  or  left 
until  the  two  images  of  the  mires  are 
close  together  and  equally  distinct. 
Rotate  the  outer  tube  (Fig.  454,  d) 
until  the  long  meridian  lines  of  the 
images  are  exactly  in  line  with  each 
other.  If  there  is  no  astigmatism, 
this  will  be  seen  at  all  axial  posi- 
tions ;  if  there  is  astigmatism,  at  only 
two  positions.  An  axis  having  thus 
been  obtained,  the  graduated  disc 
(Fig.  453,  A)  on  either  side  of  the 
tube  is  rotated  until  the  shorter  lines 
or  spurs  of  the  images  also  unite, 
forming  a  perfect  cross  with  the  longer  ones  (Fig.  455),  and  the  adjust- 
able pointer  on  the  left-hand  disc  is  made  to  coincide  with  the  stationary 
one  and  a  reading  taken.  Now  rotate  d  through  90  degrees;  the  long 
axial  lines  of  the  images  will  be  in  alignment  without  further  adjustment. 
But  if  the  eye  is  astigmatic,  the  short  lines  will  not  (Fig.  456).  By 
rotating  A,  the  short  lines  are  made  to  coincide,  so  that  a  perfect  cross 
is  again  formed,  and  the  graduation  is  read.  The  difference  between 
this  and  the  previous  reading — i.e.,  the  difference  between  the  two 
pointers — gives  the  difference  in  the  curvature  of  the  cornea  in  the  two 
meridians.  The  images  of  circles  which  form  the  outer  portion  of  the 
mires  are  oval  in  ordinary  astigmatism. 


Fig.  453. — Ophthalmometer,  as  seen 
from  behind  the  Patient.  B,  blind 
for  covering  the  eye  not  being  ex- 
amined; H,  chin-rest;  A,  A,  gradu- 
ated discs  on  which  radii  of  curva- 
ture of  the  cornea  in  various  meri- 
dians are  read  off  or  their  equivalent 
in  diopters ;  E,  eye -piece  of  telescope ; 
C,  milled  head  for  raising  and  lower- 
ing chin-rest;  F,  milled  head  for 
adjusting  height  of  the  ophthalmo- 
meter, and  G  for  moving  it  horizon- 
tally back  and  forth;  n,  graduated 
disc  for  giving  the  rotation  of  the 
outer  tube  of  the  telescope  and  the 
black  disc  u.  In  «  are  seen  the  two 
illuminated  mires. 


PRACTICAL  EXLRCISES 


1063 


7.  Spherical  Aberration.— Close  one  eye,  and  brinf;  a  small  object 
(a  pin  or  the  point  of  a  pencil)  towards  the  <jther  eye  till  it  becomes 
blurred.  Interix)se  between  the  object  and  the  eye  a  card  jK-rforated 
by  a  small  hole.  The  object  becomes  more  distinct  owing  to  the 
cutting?  off  of  the  peripheral  rays  (p.  987). 

8.  Chromatic  Aberration.— Look  at  Fig.  406  (p.  988)  from  a  distance 
too  small  for  perfect  accommodation,  and  verify  the  facts  given  in 
the  description  of  the  figure. 


Fig.  454- — Vertical  Section  of  Ophthalmometer.  d,  outer  tube  of  the  telescope 
rotating  in  sleeve  or  collar  s  (supported  by  siamUrd  /,  which  is  swivelled  in 
tubular  support,  g);  k,  diaphragm;  10,  eye-piece  with  lenses  a  and  ft;  m.  a  station- 
ary disc,  borne  on  collar  5,  graduated  to  indicate  angle  of  rotation  of  w.  a  black 
concave  disc  rotating  with  tube  d,  and  having  fixed  in  it  two  illuminated  figures 
(or  mires),  tt'.  «^, whose  images  retlerted  from  the  cornea  are  observed:  1  is  a  pointer 
carried  on  the  tube  d  which  shows  on  the  graduated  arc  the  amount  of  rotation; 
12.  12,  hemispherical  sliells  containing  small  incandescent  lamps  U)T  illuminating 
the  translucent  mires.  The  lamps  are  connected  with  wires  running  in  the 
hollow  stem  < ;  /  is  the  inner  tube  of  the  telescope  carn,-ing  the  double  prism,  h,  h. 
By  means  of  the  rack  0,  projecting  through  the  slot  m,  and  engaged  by  the  pinion 
p,  f  is  moved  back  and  forth  in  the  outer  tube,  thus  approximating  or  separating 
the  corneal  images  of  the  mires.  On  the  axis  of  />  is  a  milled  head  for  turning  it. 
and  two  duplicate  discs  graduated  with  a  scale  showing  the  radii  of  curvature 
of  the  cornea  in  millimetres,  and  another  scale  showing  their  equivalent  in 
diopters. 


Q.  Measurement  of  the  Extent  of  the  Field  of  Vision. —  Use  the  peri- 
meter shown  in  l'"ig.  430  (p.  loiS). 

(i)  For  Whtte  Light.— V'\-k  in  the  holder,  Ob.  on  the  gnidiin'cd  arc, 
a  small  piece  of  white  pajier,  and  put  one  of  the  charts  supiilicd  with 
the  instrument  at  tlie  back  of  the  wheel  which  revolves  witli  the  arc. 
The  observations  can  be  recorded  on  this  chart.  The  patient  rests  liis 
chin  on  K  and  adjusts  one  eye  against  O.  This  eye  is  kept  fixe<l  on 
the  mark  at /during  the  whole  period  of  observation,  and  the  other  eye 


1064 


THE  SENSES 


is  covered.  The  arc  is  placed  in  a  definite  position,  and  the  white 
object  gradually  moved  from  the  end  of  the  arc  until  the  person  an- 
nounces that  he  can  just  see  it.  The  angle  at  which  this  occurs  is  read 
off  and  recorded  on  the  chart.  The  arc  is  then  rotated  into  a  new 
position  and  the  observation  repeated.  A  line  is  drawn  through  all 
the  points  thus  obtained,  and  this  constitutes  the  boundary  of  the 
field  of  vision  (Fig.  431). 

If  the  position  of  each  point  is  inserted  on  the  chart,  a  point  above 
the   horizontal   plane   passing  through   the   visual  axis   being  placed 


Fig-  455. 


Fig.  456. 


below  it,  and  a  point  to  the  right  of  the  vertical  plane  being  moved  to 
the  left,  we  obtain  a  map  of  the  sensitive  portion  of  the  retina.  Usually 
perimeters  are  arranged  to  do  this  automatically. 

(2)  Repeat  the  mapping  of  the  field,  using  coloured  papers  (red, 
green,  and  blue)  instead  of  white. 

10.  Mapping  the  Blind  Spot. — Make  a  black  cross  on  a  piece  of  white 
paper  attached  to  the  wall,  the  centre  of  the  cross  being  at  the  height 
of  the  eye  in  the  erect  position.     Stand  about  12  inc-hcs  from  the  wall, 

the  chin  supported  on 
a  projecting  piece  of 
wood.  Fix  the  centre 
of  the  cross  with  one 
eye,  the  other  being 
closed,  and  move  over 
the  paper  a  pencil 
covered,  except  at  the 
point,  with  white 
paper,  until  the  point 
j  ust  disappears .  Make 
a  mark  on  the  paper 
at  this  point ,  and  repeat 
the  observation  for  all 
diameters  of  the  field. 
The  blind  spot  is  thus 
marked  out  (Fig.  457). 
Its  shape  is  not  the  same  in  all  eyes  (Fig.  458).  Its  size  and  distance 
from  the  fovea  centralis  can  be  calculated  from  the  construction  given 
in  Fig.  401  (p.  979). 

11.  The  Macula  Lutea,  or  Yellow  Spot. — (i)  After  closing  the  eyes 
for  a  minute  or  two,  look  with  one  eye  through  a  strong  solution  oi 
chrome  alum  in  a  clear  glass  bottle  with  parallel  sides.  Hold  the  bottle 
between  the  eye  and  a  white  screen  or  a  white  cloud.  An  oval  rose- 
coloured  spot  will  be  seen  in  a  greenish  field.  .  The  pigment  of  the 
yellow  spot  absorbs  the  blie  and  green  rays. 


Fig.  457. — Map  of  Blind  Spot  (reduced  by  One-half). 
Right  eye.     Distance  of  eye  from  paper  12  inches. 


PRACTICAL  EXERCISES 


io»i5 


(2)  Keep  the  eye  closed  for  a  short  time.  Then  direct  it  to  a  surface 
illuminated  by  a  weak  l)hie  light.  A  dark  blue  or  aln-ost  black  spot 
(Maxwell's  spot),  corresponding  to  tlu>  macula,  is  :  cen  in  th  •  visual 
field,  owing  to  the  absorption  of  the  blue  rays. 


Fig.  458. — Composite  picture  oi  Blind  Spot  (not  reduced).  The  Mind  sjvit  of  the 
right  eye  was  mapped  by  31  men.  the  eye  l)cing  always  at  a  distance  of  12  inches 
from  the  paper.  The  maps  were  then  superposed.  The  amount  of  white  at 
any  point  of  the  figure  is  intended  to  correspond  to  the  number  of  maps  which 
overlapped  at  that  point.  Although  the  mechanical  process  of  reproduction 
gives  rather  an  imperfect  view  of  the  composite  map,  the  area  in  the  rx*ntre  of 
the  figure  where  the  white  is  most  continuous,  and  which  represents  the  shape 
of  the  majority  of  the  blind  spots,  evidently  bears  a  general  resemblance  to  the 
outline  in  Fig.  .157. 

12.  Ophthalmoscope — (i)  Human  Eye  (p.  991). — I-et  A  be  the  ob- 
server, and  B  the  person  whose  eye  is  to  be  examined.  A  and  B 
are  seated  facing  each  otiier.  Suppose  that  the  right  eve  of  B  is  to 
be  examined.  Close  to  the  loft  ear  of  B  is  a  lamp  on  a  level  with  his 
eyes:  the  room  is  otherwise  dark.  For  a  clinical  examination,  the  ptipil 
should  be  dilated   by  putting  into  the  eye  a  drop  of  a  0-5   per  cent. 


io66  THE  SENSES 

solution  of  atropine  sulphate,  but  this  is  not  indispensable  for  the 
experiment. 

(a)  Direct  Method. — A  takes  the  mirror  in  his  right  hand,  and, 
holding  it  close  to  his  own  eye,  looks  through  the  central  hole,  and 
throws  a  beam  of  light  into  B's  eye.  A  red  glare,  the  so-called  '  reflex  ' 
from  the  choroidal  vessels,  is  now  seen.  A  then  brings  the  mirror 
to  within  2  or  3  inches  of  B's  eye,  keeping  his  own  eye  always  at  the 
aperture.  A  and  B  both  relax  their  accommodation,  as  if  they  were 
looking  away  to  a  distance.  If  both  eyes  are  emmetropic,  the  retinal 
vessels  will  be  seen.  B  should  now  look  away  past  the  little  finger  of 
A's  right  hand.  This  causes  slight  inward  rotation  of  B's  eye,  and 
brings  into  view  the  white  optic  disc  with  the  central  artery  and  vein 
of  the  retina  crossing  it. 

[b)  Indirect  Method. — A  takes  the  mirror  in  his  right  hand  to  ex- 
amine B's  right  eye,  places  his  own  eye  behind  the  aperture  as  before 
at  a  distance  of  about  18  inches  from  B,  and  throws  a  beam  of  light 
into  B's  eye.  Then  A  takes  a  small  biconvex  lens  in  his  left  hand,  and 
places  it  2  or  3  inches  in  front  of  B's  eye,  keeping  it  steady  by  resting 
his  little  finger  on  B's  temple.  A  now  moves  the  mirror  until  he  sees 
the  optic  disc. 

(2)  Examine  a  rabbit's  eye  by  the  direct  and  indirect  method. 
Dilate  the  pupil  by  a  drop  or  two  of  atropine  solution. 

For  practice,  before  doing  (i)  and  (2)  the  student  should  examine 
an  artificial  '  eye  '  by  both  methods,  so  as  to  get  a  clear  view  of  what 
represents  the  retina.  A  substitute  for  the  artificial  eye  may  be  made 
by  unscrewing  the  lower  lens  of  the  eyepiece  of  a  microscope,  and 
fastening  in  its  place  a  piece  of  paper  with  some  printed  matter  on  it. 
The  letters  must  be  made  out  with  the  ophthalmoscope. 

The  opportunity  should  also  be  taken  to  observe  the  eye  of  an 
anaesthetized  animal  by  the  simple  cover-glass  method  mentioned 
in  I  (p.  1058).  Around  cover-glass  is  slipped  under  both  eyelids  and  so 
held  in  position  on  the  cornea.  The  fundus  of  the  eye  can  now  be 
clearly  seen,  including  the  optic  disc  and  retinal  vessels.  The  instilla- 
tion of  a  little  cocaine  into  the  eye  of  a  rabbit  will  produce  local  an- 
aesthesia sufficient  to  permit  the  experiment. 

13.  Skiascopy  or  Retinoscopy. — The  simplest  method  is  as  follows: 
The  observer  places  himself  at  a  distance  of  a  metre  from  the  observed 
eye,  which  he  illuminates  by  a  beam  reflected  from  a  concave  ophthal- 
moscopic mirror  held  in  front  of  his  eye.  The  accommodation  of  the 
observed  eye  is  relaxed.  If,  now,  when  the  mirror  is  rotated  no  direc- 
tion of  movement  of  the  shadow  or  the  light  area  (p.  995)  can  be  made 
out,  the  pupil  becoming  all  at  once  dark  throughout  its  whole  extent 
when  the  mirror  is  rotated  in  one  direction,  and  all  at  once  light 
throughout  its  whole  extent  when  the  mirror  is  rotated  in  the  opposite 
direction,  the  observer  is  in  the  far-point  of  the  observed  eye.  Since 
the  far-point  is  at  the  distance  of  a  metre,  there  is  in  this  case  myopia 
amounting  to  one  diopter.  If,  however,  the  light  area  moves  in  the 
same  direction  as  the  rotation  of  the  concave  mirror,  the  far-point  of 
the  observed  eye  lies  between  the  observer  and  the  observed  eye,  so 
that  the  myopia  amounts  to  more  than  one  diopter.  The  precise 
degree  of  myopia  can  be  estimated  by  interposing  biconcave  lenses  of 
different  strength  until  the  far- point  is  made  just  i  metre. 

If  the  light  area  moves  in  the  opposite  direction  to  the  rotation 
of  thi  mirror,  the  far-point  is  more  than  a  metre  distant,  and  therefore 
the  observed  eye  is  emmetropic  or  hypermetropic,  or  myopic  to  a  degree 
less  than  a  diopter.  The  lens,  convex  or  concave,  can  now  be  sought 
out  which  will  just  bring  the  far-point  to  a  metre,  and  from  the  strength 


PRA  C  TIC  A  L  EXERCISES 


1067 


of  it,  minus  one  diopter,  the  refraction  can  be  estimated.  Suppose, 
for  instance,  that  a  convex  lens  of  two  diopters  is  required,  then  hypcr- 
metropia  of  one  diopter  exists. 

In  order  to  facilitate  the  introduction  ol  the  various  lenses,  instru- 


Fig 


459— Geneva  Retinoscope  and  Ophthalmoscope.  A,  frame  of  instrument: 
B,  retinoscope  attachment;  C,  ophthalmoscope  attachment;  D,  base;  i,  mirror 
handle;  2,  clip  to  hold  the  propar  lens  to  correct  the  abnormality  of  refraction 
of  observer  or  patient  whei  viewing  the  retina  with  the  ophthalmoscope;  3.  scal3 
indicating  the  meridian  of  handle  and  pointer;  4.  ring  in  which  mirror  cup  rotates; 
6,  mirror;  7,  mirror  spring  for  reflecting  the  light  to  a  given  point;  8,  screws  for 
adjusting  mirror;  9,  screw  for  holding  light  and  ring  4  in  position;  xo.  handle 
for  s\vinging  A  from  side  to  side;  13.  openiag  in  iris  diaohragm,  controlled  by 
handle  14;  15,  lamp  hood;  17.  knurled  handle  for  rotating  disc  ojntaining  the 
full  diopter  lenses;  18,  haadle  for  rotating  the  disc  c  ):itaining  the  fractional 
lenses  (white  numbers  indicate  plus  lenses,  and  red  minus  lenses);  20.  openiag 
through  which  observer  looks  when  adjusting  the  retinoscope  to  the  patient's 
eye;  21,  pinion  for  advancing  or  retracting  instrument;  24,  bracket  ring  of 
retinoscope  attachment  B.  which  is  slipped  o\'er  ring  25  when  putting  retinoscope 
attachment  into  place;  28.  clips  for  '  fogging '  lenses  through  which  the  patient 
looks  to  relax  accommodation;  29,  opening  through  which  the  pupil  is  viewed  in 
retinoscopy;  30,  opening  containing  clip  in  which  extra  lenses  may  be  ins.-rted 
when  required,  or  the  defect  is  over  8  diopters;  32.  patient's  eye-cup;  33,  ring  of 
ophthalmoscope  attachment  C,  which  telescopes  over  25;  34.  ophthalmoscope 
tube;  35,  binding-screw  which  holds  the  instrument  in  a  fixed  position  when 
retinoscope  is  being  used;  37,  rack  to  raise  and  lower  the  instrument;  40.  handle 
controlling  height  of  chin-rest  44;  46.  forehead-rest. 


ments  called  skiascopes  or  retinoscopes  may  be  used,  one  of  which  is 
shown  in  Fip;.  459. 

14.  Pupiilo-diiator  and  Constrictor  Fibres. — (a)  Set  up  an  induction 
machine  arranged  for  tetanus,  and  connect  a  pair  of  electrodes  through 


io68  THE  SENSES 

a  short-circuiting  key  with  the  secondary.  Etherize  a  cat  by  putting 
It  into  a  large  vessel  with  a  lid,  slipping  into  the  vessel  a  piece  of  cotton- 
wool soaked  with  ether,  and  waiting  till  the  movements  of  the  animal 
inside  the  vessel  have  ceased.  Then  quickly  put  the  cat  on  a  holder 
and  maintain  anaesthesia  with  ether.  Expose  the  vago-sympathetic 
in  the  neck  (pp.  201,  210);  the  carotid  is  taken  as  the  guide  to  it. 
Ligature  the  nerve  and  cut  below  the  ligature.  On  stimulating  the 
upper  (cephalic)  end,  the  pupil  of  the  corresponding  eye  dilates. 

Carefully  separate  the  sympathetic  from  the  vagus,  and  repeat  the 
observation  on  the  former.     The  result  on  the  pupil  is  the  same. 

{b)  Observe  in  the  eye  of  a  fellow-student,  or,  by  means  of  a  looking- 
glass,  in  your  own  eye,  that  when  light  falls  on  one  eye  both  pupils 
contract. 

(c)  Observe  that  when  the  eye  is  accommodated  for  a  near  object  the 
pupil  contracts,  and  that  it  dilates  when  a  distant  object  is  looked  at. 

15.  Colour-Mixing. — (a)  Arrange  a  red  and  a  bluish-green  disc  on 
one  of  the  steel  discs  of  the  colour-mixing  apparatus  shown  in  Fig.  460, 
so  that  a  part  of  each  is  seen.  On  another  arrange  a  violet  and  a  yellow 
disc,  and  on  the  third  an  orange  and  a  blue  disc.  By  adjustment  of 
the  proportions  of  the  two  colours  a  uniform  grey  can  be  obtained 
from  each  of  these  combinations  (complementary  colours)  when  the 
discs  are  rapidly  rotated. 

(6)  Mix  two  colours  that  are  not  complementary — e.g.,  blue  and  red — 
grey  or  white  cannot  be  obtained  by  any  adjustment  of  proportions; 
the  result  is  always  a  mixed  colour,  the  precise  hue  depending  on  the 
amount  of  each  ingredient. 

(c)  Take  papers  of  any  three  colours  from  widely-separated  parts  of 
the  spectrum — e.g.,  blue,  green,  and  red — and  arrange  them  on  one 
of  the  rotating  discs.  By  varying  the  proportions,  white  (grey)  can  be 
produced,  and  any  other  coloured  paper  fastened  on  another  of  the 
rotating  discs  can  be  matched  by  adding  white  to  the  three  colours. 

16.  After-images — (i)  Positive. — (a)  Rest  the  eyes  for  two  or  three 
minutes  by  closing  them,  or  by  going  into  a  dark  room.  Then  look  for 
an  instant  at  a  bright  object,  a  window  or  an  incandescent  lamp,  and 
at  once  close  the  eyes  again.  A  bright  positive  after-image  of  the 
object  looked  at  will  be  seen. 

{b)  Look  at  an  incandescent  lamp  through  a  coloured  glass  as  in  (a). 
The  positive  after-image  will  appear  in  the  same  colour  as  the  glass. 

(2)  Negative  After-Image. — (a)  Look  at  an  incandescent  lamp  for 
thirty  seconds,  and  then  direct  the  eyes  to  a  white  surface.  The 
after-image  of  the  filament  will  appear  dark. 

[b)  Look  at  the  lamp  through  a  coloured  glass  for  thirty  or  forty 
seconds,  and  then  close  the  eye  or  look  at  a  white  ground.  The  after- 
image of  the  filament  will  appear  in  the  complementary  colour  of  the  glass. 
If  the  glass  was  red.  for  instance,  the  after-image  will  be  greenish. 

[c)  Look  at  a  white  square  on  a  dark  ground  for  thirty  seconds, 
then  quickly  cover  the  field  with  white  paper.  A  dark  square  will  be 
seen  on  the  white  ground. 

[d)  Repeat  (c)  with  coloured  squares.  The  after-image  of  the 
square  will  be  in  the  complementary  colour. 

Contrast. — Perform  Meyer's  experiment  (p.  1016). 

17.  Retinal  Fatigue. — Fix  the  eye  steadily  on  a  portion  of  a  printed 
page  a  considerable  distance  away.  Note  that  the  print  soon  be- 
comes blurred.  Wink  the  eye;  the  short  rest  causes  a  notable  recovery 
of  the  retina. 

18.  Visual  Acuity. — Draw  on  a  white  card  a  series  of  vertical  black 
lines  I  millimetre  thick,  and  separated  from  each  other  by  a  distance 


PRACTICAL  EXERCISES 


1069 


of  a  milhrnetre.  Set  the  card  up  in  a  good  light,  and  walk  backwards 
irom  It  till  the  individual  lines  just  fail  to  be  discriminated.  Measure 
the  distance  from  tha  card  at  which  this  occurs,  and  calculate  the  hize 
ot  the  retinal  iinaf,'e  (p.  979). 

19.  Colour-Blindness.— Spread  out  HolniRren's  coloured  wools  on 
a  sheet  of  white  filter-paper  in  a  good  light.  Do  not  mention  the 
colours  of  any  of  the  wools,  but  (i)  ask  the  person  who  is  l>emg  tc-sted 
to  pick  out  all  the  wools  which  seem  to  him  to  match  a  pale  pure  green 
wool  (neither  yellow  green  nor  blue  green),  which  is  hantled  to  him. 
He  IS  not  to  make  an  exact  match,  but  to  pick  out  the  skeins  which 


Fig.  460. — Apparatus  for  Colour-Mixing. 

seem  to  have  the  same  colour.  If  he  makes  any  mistakes,  by  selecting, 
e.g.,  in  addition  to  the  green  skeins,  any  of  the  '  confusion  colours.' 
such  as  grey,  greyish-yellow,  or  blue  wools,  there  is  some  defect  of 
colour  discrimination.  To  determine  whether  the  {x-rson  is  red  or  green 
blind,  tests  (2)  and  (3)  are  then  made.  (2)  Ciive  him  a  medium  purple 
(magenta)  wool,  and  ask  him  to  pick  out  matches  for  it.  If  he  u  red- 
blind,  he  will  select  as  matches  to  it  only  blues  and  violets,  as  well  as 
other  purples.  If  he  is  green-bliiMl,  he  will  select  only  greens  and 
greys.  (3)  The  third  test  is  a  red  wool.  In  selecting  matches  for  this, 
tlie  red-blind  will  choose  (with  reds)  greens,  graj-s,  or  browns  less  bright 


I070  THE  SENSES 

than  the  test.     The  green-blind  will  choose  (with  reds)  greens,  greys, 
or  browns  which  are  brighter  than  the  test. 

It  must  be  remembered  that  the  results  of  tests  with  the  coloured 
wools  need  not  be  precisely  the  same  as  those  with  coloured  lights, 
and  that  when  there  is  a  discrepancy  between  the  two  the  test  with 
the  coloured  lights  should  be  accepted ;  for  it  is  usually  the  normal 
perception  and  discrimination  of  coloured  lights  which  has  practical 
importance. 

20.  Talbot's  Law. — Rotate  a  disc  one  sector  of  which  is  black  and  the 
rest  white,  or  a  disc  like  that  in  Fig.  427  (p.  loii).  A  uniform  shade  is 
produced  as  soon  as  a  speed  of  about  25  revolutions  a  second  has  been 
attained,  and  this  is  not  altered  bj'  further  increase  in  the  speed. 

21.  Purkinje's  Figures. — [a)  Concentrate  a  beam  of  sunlight  by  a 
lens  on  the  sclerotic  at  a  point  as  far  as  possible  from  the  corneal  margin, 
passing  the  beam  through  a  parallel-sided  glass  trough  filled  with  a 
solution  of  alum  to  sift  out  the  long  heat-rays.  The  eye  is  turned 
towards  a  dark  ground.  The  field  of  vision  takes  on  a  bronzed  appear- 
ance, and  the  retinal  bloodvessels  stand  out  on  it  as  a  dark  network, 
which  appears  to  move  in  the  same  direction  as  the  spot  of  light  on  the 
sclerotic.  A  portion  of  the  field  corresponding  to  the  yellow  spot  i? 
devoid  of  shadows  (p.  1003). 

(6)  Direct  the  eyes  to  a  dark  ground  while  a  flame  held  at  the  side  of 
the  eye,  and  at  a  distance  from  the  visual  line,  is  moved  slightly  to  and 
fro.  A  picture  of  branching  bloodvessels  appears.  This  experiment 
is  performed  in  a  dark  room. 

\c)  Immediately  on  awaking  look  at  a  white  ceiling  for  an  instant; 
a  pattern  of  branched  bloodvessels  is  seen.  If  the  eye  be  at  once  closed, 
and  then  opened  with  a  blinking  movement,  this  may  be  observed  again 
and  again.     Ultimately  the  appearance  fades  away. 

HEARING,  TASTE,  SMELL,  TOUCH,  ETC. 

22.  Monochord. — Study  by  means  of  the  monochord,  a  stretched 
string  with  a  movable  stop,  the  relation  between  the  pitch  of  the  note 
given  out  by  a  vibrating  string,  and  its  length  and  tension. 

23.  Beats.— Cause  two  tuning-forks  of  nearly  equal  pitch  to  vibrate  at 
the  same  time.     Make  out  the  beats,  and  count  their  number  per  second. 

24.  Sympathetic  Vibration. — Take  three  tuning-forks  mounted  on 
resonators.  Let  two  of  them  be  of  the  same  pitch.  Strike  one  of 
these;  the  other  is  thrown  into  sympathetic  vibration,  and  continues 
to  give  out  a  note  after  the  first  is  quickly  stopped  by  touching  it. 
The  third  fork  is  unaffected. 

25.  Determine  by  means  of  Galton's  whistle  the  pitch  of  the  highest 
audible  tone. 

26.  Cranial  Conduction  of  Sound. — When  a  tuning-fork  is  held 
between  the  teeth,  a  part  of  the  sound  passes  out  of  the  ear  from  the 
vibrating  membrana  tympani;  if  one  ear  is  closed,  the  sound  is  heard 
better  in  this  than  in  the  open  ear.  If  the  tuning-fork  is  held  between 
the  teeth,  till,  with  both  ears  open,  it  becomes  inaudible,  it  will  be 
heard  for  a  short  time  if  one  or  both  ears  be  stopped ;  and  when  in  this 
position  the  sound  again  becomes  inappreciable,  it  can  still  be  caught 
if  the  handle  be  introduced  into  the  auditory  meatus. 

27.  Tciste. — (i)  Apply  to  the  tongue  by  means  of  a  camel's-hair 
brush  a  solution  of  quinine  (i  to  1,000),  sodium  chloride  (i  to  200), 
cane-sugar  (i  to  50"),  and  sulphuric  acid  (i  to  1,000).  Determine  at 
what  part  of  the  tongue  the  strongest  sensations  are  elicited  by  each. 


PliACriCAL  EXEUCISLS  1071 

(2)  Prepare  a  scries  of  solutions  of  sulphuric  at  id  of  gnidually  in- 
creasing strength,  beginning  with  a solution  (a   two-thousandth 

,  2,<JJO  ^ 

gramme-molecular  solution)  (p.  420).  Put  into  the  mouth,  after 
previous  rinsing  with  distilled  water.  4  or  5  c.c.  of  one  of  the  solutions 
of  the  acid,  beginning  with  the  weakest,  and  determine  at  what  con- 
centration of  the  H  ions  the  acid  taste  first  appears,  rinsing  out  the 
mouth  after  each  observation.  Repeat  the  exjKriment  with  sf^lutions 
of  hydrochloric  acid,  and  determine  whether  the  threshold  value  is  the 
same. 

A  similar  comparison  of  the  necessary  concentration  of  the  Uli 
ions  can  be  made  with  solutions  of  sodium  hydroxide  and  potassium 
hydroxide. 

(3)  Connect  two  short  pieces  of  platinum  wire  with  the  copjx-r  wire 
from  the  poles  of  a  Daniell  or  dry  cell.  Apply  one  platinum  wire  to 
the  inner  surface  of  the  lip  and  the  other  t(/the  tip  of  the  tongue. 
Reverse  the  poles.  Note  the  difference  in  the  sensation  according  to 
whether  the  anode  or  the  kathode  is  on  the  tongue. 

28.  Smell. — (i)  Pass  a  current  through  the  olfactory  mucous  mem- 
brane by  connecting  one  electrode  with  the  forehead  and  the  other 
by  means  of  a  small  piece  of  sponge  or  cotton-wool  soaked  in  physio- 
logical salt  solution  with  one  nostril.  An  odour  like  that  of  phosphorus 
will  be  perceived. 

(2)  To  distinguish  between  Taste  and  Smell. — Use  a  solution  of  clove- 
oil  in  water  which  can  just  be  distinguished  from  water  when  it  is  placed 
on  the  tongue  by  means  of  a  camel's-hair  brush.  Close  the  nostrils, 
and  determine  whether  the  clove-oil  can  now  be  detected. 

29.  Touch  and  Pressure. — (i)  Prepare  a  number  of  hair  aesthesio- 
meters  by  fastening  hairs  of  different  thicknesses  to  small  woo<len 
handles  about  3  inches  long  by  means  of  sealing-wax.  Hairs  as  straight 
as  possible  should  be  chosen,  or  straight  portions  of  hairs.  The  hair  is 
to  be  fastened  on  one  end  of  the  piece  of  wood  at  right  angles  to  the 
long  axis  of  the  handle,  so  that  about  an  inch  of  the  hair  projects  to 
one  side.  Determine  the  pressure  value  of  each  hair  by  pressing  it 
down  upon  the  scale  of  a  balance  till  it  is  slightly  bent,  and  observing 
the  greatest  weight  in  the  other  scale  which  it  will  lift.  Mark  the 
number  in  milligrammes  on  the  handle.  In  this  way,  when  a  hair  is 
placed  at  right  angles  to  a  point  of  the  skin,  and  pressure  exertetl  on 
it  till  it  begins  to  bend,  the  intensity  of  the  touch  stimulus — i.e..  the 
pressure  exqrted  on  the  skin — is  definitely  measured,  and  by  using 
hairs  of  different  pressure  values  the  threshold  value  of  the  stimulus 
for  any  touch  area — i.e.,  the  pressure  which  just  gives  the  sensation 
of  light  touch — can  be  determined  (p.  1041). 

(a)  Using  the  back  of  the  hand,  note  how  light  a  touch  of  the  asthesi- 
ometer  applied  to  the  end  of  a  hair  suffices  to  elicit  a  sensation  of  touch, 
as  compared  with  a  part  free  from  hairs.  The  hairs  diminish  the 
threshold  of  the  stimulation  by  acting  as  levers,  whose  short  arm 
presses  against  the  nerve-endings  surrounding  the  hair-follicles,  while 
the  stimulating  weight  acts  on  the  long  arm.  When  the  skin  is  shaved 
the  threshold  is  always  raised. 

{b)  Shave  an  area  on  the  back  of  the  hand,  and  make  out  the  relation 
of  the  touch-spots  to  the  hair  follicles,  luich  hair  has  an  csiKxially 
sensitive  touch-spt^t  just  on  the  '  windward  '  side  of  the  follicle  (p.  1040). 
Using  lesthesiomctcrs  of  ditTerent  pressure  values,  determme  the 
threshold  value  for  the  shaved  area.  Outluie  an  area  of  a  square 
centimetre  on  the  skin,  and  determine  the  numlx-r  of  touch-spots, 
using  first  a  hair  of  the  threshold  value,  and  then  going  over  the  area 


I072  THE  SENSES 

again  with  a  hair  of  a  decidedly  higher  pressure  vahie.  The  threshold 
value  for  many  parts  of  the  hair^-  skin  is  obtained  with  a  hair  which 
bends  at  70  milligrammes.  Repeat  the  determinations  for  other  skin 
areas,  such  as  the  back  of  the  upper  arm,  the  palm  of  the  hand,  the 
anterior  surface  of  the  leg,  the  chest,  the  back,  and  the  cheek,  forehead, 
and  lips. 

It  is  well  that  the  subject  should  be  blindfolded  during  the  ex- 
amination of  the  skin  areas.  He  should  understand  by  preliminary 
practice  what  the  sensation  of  light  touch  is,  the  perception  of  which 
he  is  to  indicate.  With  strong  aesthesiometer  hairs  the  pricking  sen- 
sation due  to  stimulation  of  pain-spots  must  be  discriminated  from 
touch  sensation.  When  the  two  sensations  are  elicited  together,  the 
touch  sensation  is  momentary^  and  the  subject  must  be  alert  to  detect 
it  immediately  on  stimulation.  The  pain  sensation  develops  more 
slowly,  but  lasts  longer  and  becomes  much  more  conspicuous  than  the 
touch  sensation,  which  accordingly  is  apt  to  be  submerged  by  it  in 
consciousness. 

(2)  Touch  the  skin  with  a  blunt  point  (at  or  about  skin  temperature). 
With  light  contact  the  sensation  is  that  of  simple  touch.  On  in- 
creasing the  pressure,  the  quite  distinct  sensation  of  deep  pressure  is 
perceived. 

(3)  Touch  a  portion  of  skin  with  a  camel's-hair  brush  of  ordinary 
size,  pressing  on  it  till  the  hairs  of  the  brush  begin  to  bend.  The  first 
sensation  of  simple  contact  gives  place  to  a  sensation  of  pressure.  Re- 
peat with  a  camel's-hair  brush  of  the  finest  hairs  half  a  centimetre  in 
length,  cut  away  till  its  cross  section  is  only  half  a  millimetre  in  diameter 
at  the  base.  Probably  a  pure  sensation  of  touch,  without  any  pressure 
element,  will  be  obtained  when  the  brush  is  applied  so  as  just  to  bend 
the  hairs. 

(4)  Find  the  least  distance  apart  at  which  the  points  of  the  aesthesi- 
ometer compasses  can  be  recognized  as  two  when  applied  to  the  back  of 
the  hand,  the  forearm,  upper  arm,  forehead,  finger-tips,  or  tip  of  the 
tongue.  Both  points  of  the  compasses  must  be  placed  on  the  skin 
at  the  same  time,  and  the  same  pressure  applied  to  both.  The  subject 
must  not  see  the  points. 

(5)  Time  Discrimination  of  Touch. — Touch  the  prong  of  a  vibrating 
tuning-fork  lightly  with  the  tip  of  the  finger.  The  taps  of  the  prong 
on  the  skin  do  not  blend  into  a  continuous  sensation  even  when  the 
fork  vibrates  several  hundred  times  per  second. 

30.  Temperature  Sensations. — For  the  investigation  of  these,  pieces 
of  thick  copper  wire,  filed  at  one  end  to  a  blunt  point,  and  fixed  by 
the  other  in  a  small  wooden  handle,  may  be  used.  They  can  be  heated 
in  a  sand-bath  or  in  a  beaker  of  water  to  the  desired  temperature,  or 
cooled  in  cold  water  or  in  ice.  Or  a  metal  tube  drawn  out  at  one  end, 
through  which  water  at  the  required  temperature  can  be  passed  before 
use,  may  be  employed.  Another  device  is  a  metal  cylinder  ending  in 
a  point,  and  filled  with  water  at  the  given  temperature. 

(i)  On  the  dorsal  side  of  the  hand  outline  an  area  of  skin  with  a 
pen  or  a  coloured  pencil.  Divide  this  into  areas  of  4  square  milli- 
metres. Go  over  the  area  with  a  wire  or  cylinder  at  a  temperature  of 
about  40°  C,  and  determine  the  extent  and  position  of  the  spots  which 
on  contact  yield  a  sensation  of  warmth,  marking  them  on  the  skin  by 
ink-dots,  or  mapping  them  on  ruled  paper.  Then  repeat  the  ex- 
ploration with  points  at  a  temperature  of  about  15°  C,  and  map  the 
spots  which  yield  a  sensation  of  coolness.  Now  note  whether  a  warm 
spot  touched  with  a  point  at  15°  C,  or  a  cold  spot  touched  with  a  point 
at  40"  C,  yields  any  temperature  sensation. 


PRACTICAL  EXERCISES  1073 

(2)  Touch  the  skin  with  a  test-tube  containing  water  at  50'  C,  and 
again  with  a  test-tube  containing  ice.  Do  the  sensations  differ  in  any 
way  from  those  of  pure  warmth  and  coolness  ?  Repeat  ^i)  with 
temperatures  of  50"^  and  0°,  and  note  whether  there  is  any  difference 
in  the  quahty  of  the  sensations  yielded  by  the  warm  and  cold  spots. 
When  a  cold  spot  is  touched  with  a  point  at  a  temperature  of  50°,  or 
a  warm  spot  with  a  point  at  a  temperature  of  0°,  is  any  sensation 
obtained  ?     If  so,  what  ? 

(3)  Apply  successively  to  one  and  the  same  portion  of  the  skin  test- 
tubes  containing  water  at  50°,  45°,  40°,  35°,  30°,  25°,  20°,  15°,  10°, 
5°,  and  0°  (ice),  and  determine  the  sensations  excited  in  each  case. 
The  contact  should  only  be  momentary,  so  as  not  to  cause  extensive 
and  lasting  change  of  temperature  of  the  skin.  Note  that  there  is  a 
certain  range  of  temperature  above  and  below  that  of  the  skin  within 
which  no  sensation  of  heat  or  cold  is  given. 

(4)  Take  three  beakers  of  water  at  20°,  30°,  and  40°  C.  respectively. 
Place  a  finger  of  one  hand  in  the  coldest  beaker,  a  finger  of  the  other 
hand  in  the  warmest,  until  no  definite  temperature  sensations  are  felt 
by  either  finger.  Plunge  both  fingers  into  the  beaker  at  30°  C,  and 
temperature  sensations  will  be  perceived. 

(5)  Temperature  Discrimination. — Find  the  least  perceptible  differ- 
ence in  temperature  between  two  beakers  of  water  at  about  o"  C. 
Repeat  the  experiment  with  two  beakers  of  water  at  about  30°  C,  and 
again  with  two  beakers  of  water  at  about  55°  C.  Use  the  same  hand. 
Expose  the  same  amount  of  surface  to  the  water. 

(6)  Compare  the  acuteness  of  the  temperature  sensations  of  the 
skin  and  the  mucous  membrane  of  the  mouth,  touching  a  given  portion 
of  skin  and  then  a  portion  of  mucous  membrane  with  tubes  contaming 
water  at  various  temperatures. 

31.  Pain. — (i)  Using  a  pin,  explore  a  cutaneous  area  to  determine 
whether  every  point  of  the  skin  yields  the  painful  sensation  of  pricking. 
Especially  compare  the  result  of  stimulating  the  region  in  the  imme- 
diate neighbourhood  of  the  hairs  with  the  spaces  between  hairs.  Dis- 
criminate the  touch  sensation  given  by  the  light  contact  of  the  pin-point 
from  the  painful  impression  caused  when  the  pressure  is  increased. 
Note  that  the  touch  element  is  more  evanescent  than  the  pain  clement. 

(2)  With  strong  v.  Frey  hairs  determine  the  pressure  at  which  the 
sensation  of  touch  passes  into  that  of  pain. 

(3)  Compare  the  sensibility  to  pin-pricks  of  the  mucous  membrane 
within  the  mouth  with  that  of  the  skin. 

32.  Having  determined  the  systolic  blood-pressure  in  one  arm  of 
a  fellow-student  (p.  113),  release  the  pressure  in  the  cuff,  then  raise 
the  hand  in  the  air  so  as  to  empty  the  arm  of  blood,  and  while  it 
is  still  raised,  get  up  a  pressure  in  the  cuff  equal  to  the  systolic  pressure. 
Lower  the  hand  and  maintain  this  pressure  by  squeezing  the  bulb  occa- 
sionally. Be  careful  not  to  increase  the  pressure  alx)vc  the  systolic 
pressure.  There  is  no  disadvantage  in  letting  it  drop  5  to  10  milli- 
metres below  systolic  pressure  from  time  to  time.  Now  compare  the 
acuity  of  the  sensations  of  contact,  pressure,  warmth,  cold,  and  pain 
in  the  anaemic  and  the  normal  hand,  always  on  symmetrically  placed 
areas  of  the  two  hands.  Repeat  the  comparison  at  intervals  till  a 
definite  difference  is  found,  and  note  the  sensation  for  which  the  acuity 
first  diminishes.  Do  not  i>rolong  the  exi>criment  unduly.  If  the  sub- 
ject experiences  discomfort,  the  pressure  in  the  armlet  is  to  be  at  once 
released. 

68 


CHAPTER  XIX 
REPRODUCTION 

Regeneration  of  Tissues. — Since  cells  are  constantly  dying  within 
the  body,  they  must  be  constantly  reproduced.  In  some  tissues  the 
process  by  which  this  is  accomplished  is  more  evident,  and  therefore 
better  known,  than  in  others.  The  most  highly-organized  tissues 
are  with  difficulty  repaired,  or  not  at  all.  The  epidermis  is  always 
wearing  away  at  its  surface,  and  is  being  constantly  replaced  by  the 
multiplication  of  the  cells  of  the  stratum  Malpighii.  In  the  corneous 
layer  we  have  only  dead  cells ;  in  the  Malpighian  layer  we  have  every 
histological  gradation  from  squames  to  columns,  and  every  physio- 
logical gradation  from  cells  which  are  about  to  die  to  cells  that  have 
just  been  born.  The  corpuscles  of  the  blood  undoubtedly  arise  at 
first,  and  are  recruited  throughout  life,  by  the  proliferation  of 
mother-cells.  The  gravid  uterus  grows  by  the  formation  of  new 
fibres  from  the  old,  and  by  the  enlargement  of  both  old  and  new. 
A  severed  muscle  is  generally  united  only  by  connective  or  scar 
tissue,  but  under  favourable  conditions  a  complete  muscular 
'  sphce  '  may  be  formed.  A  broken  bone  is  regenerated  by  the 
proliferation  of  cells  of  the  periosteum,  which  become  bone- 
corpuscles.  We  do  not  know  whether  there  is  any  new  formation  of 
nerve-cells  in  the  adult  organism,  but  peripheral  nerve-fibres  which 
have  been  destroyed  by  accident  or  operation  are  readily  regenerated, 
and  the  end-organs  of  efferent  nerves  may  share  in  this  re- 
generation. 

In  lower  forms  of  animals,  and  in  all  or  most  vegetables,  the  power 
of  regeneration  is  much  greater  than  in  man.  The  starfish  can  not 
only  repair  the  loss  of  an  arm,  but  from  a  severed  arm  a  complete 
animal  can  be  developed.  A  newt  can  reproduce  an  amputated  toe, 
and  every  tissue — skin,  muscle,  nerves,  bone — will  be  in  its  place. 
After  extraction  of  the  crystalhne  lens  in  triton  larvse,  a  new  lens  is 
formed  from  the  iris  epithelium.  Artificial  mouths  surrounded  by 
tentacles  can  be  formed  in  Cerianthus,  an  animal  belonging  to  the 
same  group  as  the  sea-anemones,  merely  by  making  a  cut  in  the 
body-wall  and  preventing  it  from  closing.  In  an  Ascidian,  too  (the 
Cynone  intestinalis),  artificial  openings  in  the  branchi?.!  sac,  sur- 

I074 


REPRODUCTION  IN  THE  HIGHER  ANIMALS  1075 

rounded  by  numerous  pigmented  points  simiHir  to  the  eye-spots 
around  the  natural  mouth  and  anus,  have  been  produced  (Loeb). 

Thus,  in  a  sense,  reproduction  is  constantly  going  on  within  the 
bodies  even  of  the  higher  animals.  But  since  the  whole  organism 
eventually  dies,  as  well  as  its  constituent  cells,  a  reproduction  of  the 
whole,  a  regeneration  en  masse,  is  required. 

A  cell  of  the  stratum  Malpighii  can  only,  so  far  as  we  know, 
reproduce  a  similar  cell,  and  this  is  characteristic  of  cells  that  have 
undergone  a  certain  amount  of  differentiation,  especially  in  the 
higher  animals.  The  fertilized  ovum,  on  the  other  hand,'  has  the 
power  of  reproducing  not  only  ova  like  itself,  but  the  coimterparts 
of  every  cell  in  the  body.  And  this  is  only  tlu-  highest  devdopment 
of  a  power  which  is  in  a  smaller  degree  inherent  in  other  cells  in 
lower  forms.  Plants  and  the  lowest  animals  are  far  ler:s  dependent 
upon  reproduction  by  means  of  special  cells.  A  piece  of  a  Hydra 
separated  off  artificially  or  by  simple  fission  becomes  a  complete 
Hydra,  as  was  shown  by  Trembley  a  century  and  a  half  ago.  A 
cutting  from  a  branch,  a  root,  a  tuber,  or  even  a  leaf  of  a  plant,  may 
reproduce  the  whole  plant.  It  is  as  if  each  cell  in  these  lowly  forms 
carried  within  it  the  plan  of  the  complete  organism,  from  which  it 
built  up  the  perfect  plant  or  animal. 

Reproduction  in  the  Higher  Animals. — In  regard  to  the  secretions 
of  the  reproductive  glands,  all  that  is  necessary  to  be  said  here  is 
that,  unlike  other  secretions,  their  essential  constituents  are  living 
cells.  The  spermatozoa  in  the  male  have,  indeed,  diverged  far  from 
the  primitive  type.  Certain  cells  (spermocytes)  in  the  tubules  of  the 
testicle  divide,  each  forming  two  daughter  spermocytes.  Each  of 
the  daughter  spermocytes  in  turn  divides,  so  that  four  cells  (sperma- 
tids) are  formed  from  each  spcrmocyte.  In  the  final  division  which 
produces  the  spermatids  a  reduction  of  the  chromosomes  (p.  1079) 
occurs,  so  that  the  spermatid  possesses  only  one-half  the  number 
characteristic  of  the  somatic  cells  of  the  species.  The  spcrmatii's 
elongate  and  become  spermatozoa,  the  head  of  the  latter  repn- 
senting  the  nucleus  of  the  former;  and  it  is  this  nucleus  (with  the 
middle  piece  originally  containing  the  male  centrosome  and  attrac- 
tion sphere)  which  is  the  essential  contribution  of  the  male  to  the 
reproductive  process.  The  tail  of  the  spermatozoon  is  simply,  from 
the  physiological  point  of  view,  a  motile  arrangement ,  whose  f unct  ion 
it  is  to  carry  the  nucleus  of  the  male  element,  freighted  with  all  that 
the  father  can  transmit  to  the  offspring,  into  the  neighbourhood  of 
the  female  reproductive  element  or  ovum.  After  the  spermatozoon 
has  penetrated  the  ovum  its  tail  disappears,  being  probably 
absorbed.  The  function  of  the  accessory  reproductive  glands,  the 
prostate,  the  seminal  vesicles,  and  Cowper's  gland,  are  not  well 
understood.  But  the  spermatozoa  in  the  act  of  ejacnlation  are 
mixed  with  the  secretions  of  these  glands,  and  therefore  it  is  to  bo 


1076  REPRODUCTION 

supposed  that  they  are  of  importance.  When  the  prostate  and  the 
seminal  vesicles  are  removed  in  white  rats,  the  female  is  no  longer 
fertilized,  although  the  sexual  power  of  the  male  is  unaltered.  The 
testes  apparently  develop  spermatozoa  in  the  normal  manner,  but 
for  some  reason  they  either  do  not  reach  the  ovum  or  do  not  react 
with  it  normally  if  they  do  reach  it.  When  the  testes  are  re- 
moved from  a  young  animal,  the  development  of  the  prostate  is 
interfered  with;  in  an  adult  animal  the  gland  atrophies. 

The  ovum  also  begins  as  a  typical  cell  with  nucleus  (germinal 
vesicle),  nucleolus  (germinal  spot),  centrosome  and  attraction  sphere 
(p.  5),  and  it  forms,  by  its  repeated  subdivision,  all  the  cells  of  the 
foetal  body.  But,  except  in  some  {partheno genetic)  forms,  it  never 
awakens  to  this  reproductive  activity  till  fecundation  has  occurred ; 
and  fecundation  essentially  consists  in  the  union  of  the  male  with  the 
female  element,  or  rather  in  the  union  of  the  male  and  female  nucleus. 

From  time  to  time  a  ripe  Graafian  folUcle,  overdistended  by  its 
liquor  folliculi,  bursts  on  the  surface  of  the  ovary  and  discharges  an 
ovum.  The  common  opinion  is  that  most  ova  are  discharged  at  the 
time  of  the  menstrual  period,  but  some  writers  take  the  view  that 
the  discharge  bears  no  relation  to  menstruation.  Only  one  ovum 
seems  to  be  shed  each  month.  It  was  formerly  believed  that  the 
frayed  or  fimbriated  end  of  the  Fallopian  tube,  rising  up  finger-hke 
from  the  dilatation  of  its  bloodvessels,  grasps  the  ovum.  But  it  is 
more  than  doubtful  whether  this  occurs.  It  is  more  probable 
that  the  ovum  is  first  discharged  into  the  pelvic  cavity,  and 
is  guided  to  the  orifice  of  the  Fallopian  tube,  not  necessarily 
that  of  its  own  side,  by  the  movements  of  the  cilia  around  the 
orifice,  and  then  passed  slowly  along  the  tube  by  the  downward 
lashing  cilia  which  line  it.  Probably  the  ovum  takes  as  a  rule  eight 
or  ten  days  to  reach  the  uterus,  and  it  is  during  this  time  that 
fertilization  takes  place.  If  not  impregnated,  it  soon  perishes  amid 
the  secretions  of  the  uterus — how  soon  has  been  matter  of  discussion, 
andean  hardly  be  considered  as  settled.  If,  however,  impregnation 
occurs,  the  ovum  penetrating  the  superficial  epitheUum  into  the 
subepithelial  connective  tissue  becomes  fixed  in  one  of  the  crypts  or 
pouches  of  the  uterine  mucous  membrane  {decidua  serotina),  which 
grows  round  it  as  the  decidua  reflexa.  The  Graafian  follicle,  after 
the  discharge  of  the  ovum,  fills  up  with  blood,  and  a  cellular  struc- 
ture, the  corpus  luteum,  is  developed  in  its  interior  from  the  cells 
which  line  the  follicle.  In  the  absence  of  impregnation  the  corpus 
luteum  begins  to  disappear  before  the  next  menstrual  period,  and  is 
spoken  of  as  a  false  corpus  luteum.  But  when  pregnancy  occurs,  it 
continues  to  grow  till  the  fourth  or  fifth  month  of  pregnancy,  and  is 
called  a  true  corpus  luteum. 

Menstruation. — In  the  mature  female,  from  puberty,  the  age  at 
which  the  reproductive  power  begins  (thirteenth  to  fifteenth  year), 


MENSTRUATION  1077 

on  till  the  time  of  the  menopause  (fortieth  to  fiftieth  year),  at  which 
it  ceases,  an  ovum — or  it  may  be  in  some  cases  more  than  one — is 
discharged  at  regular  intervals  of  about  four  weeks.  This  discharge 
is  accompanied  by  certain  constitutional  symptoms  and  local  signs 
that  last  for  a  variabh-  number  of  days.  The  temperature  of  the 
body  diminishes  somewhat,  rarely  more  than  i''  F..  and  there  is 
also  a  slight  fall  in  the  pulse-rate.  The  genital  organs  are  congested, 
and  a  quantity  of  blood,  which  varies  in  different  individuals,  but 
is  usually  not  over  50  c.c,  is  shed.  If  more  than  bo  c.c.  is  lost,  the 
flow  is  copious.  Over  100  c.c.  it  is  abnormally  great  (G.  Hoppe- 
Seyler).  At  the  same  time,  the  whole  or  a  portion  of  the  mucous 
membrane  of  the  uterus  is  cast  off. 

As  to  the  physiological  meaning  of  this  menstruation,  as  it  is 
called,  opinion  is  divided.  Two  chief  theories  have  been  proposed 
to  account  for  it,  both  of  which  agree  in  considering  the  phenomenon 
to  be  connected  with  a  preparation  of  the  uterus  for  the  reception 
of  the  ovum.  But  according  to  the  theory  of  Pfliiger  the  mucous 
membrane  is  stripped  off  (by  a  process  analogous  to  the '  freshening  ' 
or  paring  of  the  indurated  edges  of  a  wound  by  the  surgeon,  in 
order  that  union  may  occur  when  they  are  brought  together)  on 
the  chance,  so  to  speak,  that  an  impregnated  ovum  may  arrive.  On  the 
alternative  theory,  this  change  takes  place  because  the  ovum  has  not 
been  impregnated,  and  the  bed  prepared  for  it  not  being  required, 
the  swollen  and  congested  uterine  mucous  membrane  undergoes 
degeneration,  and  is  in  part  cast  off  (Reichert,  Williams,  etc.). 

The  process  of  menstruation,  and  the  nutrition  of  the  genital 
organs,  especially  the  uterus,  are  intimately  dependent  upon  the 
ovaries.  There  is  good  evidence  that  the  influence  is  exerted  t  hrough 
an  internal  secretion  formed  by  some  portion  of  the  ovarian  sub- 
stance. When,  for  instance,  the  ovaries  of  young  animals  (guinea- 
pigs)  are  removed  from  their  normal  situation  and  transplant eil  to 
a  distant  part  of  the  body,  the  external  genitals,  vagina,  and  uterus 
undergo  the  normal  development  instead  of  being  arrested  in  their 
growth,  as  is  the  case  when  the  ovaries  are  removed  altogether.  The 
removal  of  the  ovaries  in  adult  animals  leads  to  fibrous  d^eneration 
of  uterus  and  Fallopian  tubes.  On  the  other  hand,  removal  of  the 
uterus  has  no  effect  on  the  development  of  the  ovaries  in  a  young 
animal,  and  docs  not  cause  degeneration  of  the  ovaries  of  an  adult 
animal.  In  monkeys,  in  which  a  menstrual  flow  comparable  to  that 
in  the  human  female  occurs,  it  was  found  that  menstruation  took 
place  after  the  ovaries  had  been  transplanted  from  their  original  seat, 
and  the  flow  stopped  when  the  transplanted  ovaries  were  removed. 
It  has  been  stated,  too,  that  in  a  young  woman  suffering  fioni 
amcnorrha?a  (lack  of  menstruation)  a  regular  flow  appeareti  aftei 
the  transplantation  of  an  ovary  from  another  woman  into  her  ut«'rus. 
Recently  the  view  has  been  put  forward  that  the  important  part  of 


1 078  REPRODUCTION 

the  ovary  for  these  functions  is  the  corpus  luteum,  which  is  by  some 
investigators  considered  to  be  a  gland  with  an  internal  secretion 
(Born).  This  secretion  seems  to  be  connected  with  the  implantation 
ol  the  ovum  and  the  subsequent  growth  of  both  ovum  and  uterus 
According  to  Fraenkel,  the  absence  of  the  corpus  luteum  prevents 
implantation.  The  experiments  of  Marshall  and  Jolly  also  indicate 
that  the  corpus  luteum  forms  some  substance,  which  exerts  an  action 
on  the  uterine  mucosa,  during  the  earlier  stages  of  pregnancy.  When 
the  ovum  has  not  been  fertilized  the  corpus  luteum  brings  about 
menstruation.  Where  fertilization  has  occurred  it  prepares  the 
uterus  for  the  implantation  of  the  ovum.  Fraenkel  considers  that 
there  is  no  difference  between  the  true  and  the  false  corpora  lutea. 
'  Lutein,'  the  dried  extract  of  the  corpora  lutea  of  cows,  is  recom- 
mended for  the  treatment  of  suppressed  menstruation,  and  the 
troublesome  symptoms  arising  from  the  premature  production  of 
the  menopause  by  removal  of  the  ovaries. 

The  mode  of  origin  of  the  corpus  luteum  has  given  rise  to  much 
discussion.  Two  chief  views  have  been  put  forward:  (i)  That  it  is 
a  structure  derived  from  the  connective-tissue  wall  (theca)  of  the 
discharged  follicle  (v.  Baer,  etc.) ;  (2)  that  it  is  developed  from  the 
follicular  epithelium  (membrana  granulosa)  (Sobotta,  etc.).  The 
second  view  seems  to  be  best  established.  The  granulosa  cells 
enlarge,  it  is  said,  without  becoming  more  numerous.  In  certain 
animals  (guinea-pig),  however,  mitotic  division  of  cells  of  the 
membrana  granulosa  has  been  observed  (L.  Loeb). 

The  influence  of  the  ovary  on  the  formation  of  the  decidua  has 
been  illustrated  in  a  very  interesting  way  by  the  investigations  of 
L.  Loeb  on  the  artificial  production  of  deciduomata.  He  has  shown 
that  if  a  number  of  incisions  are  made  into  the  uterus  of  a  rabbit  or 
guinea-pig  within  a  certain  interval  after  the  oestral  period  (period  of 
heat),  a  structure  with  the  histological  characters  of  the  decidua 
develops  at  each  wound.  Impregnation  does  not  appear  to  be  a 
necessary  factor,  nor  even  contact  of  the  ovum  with  the  uterine 
mucous  membrane.  On  the  other  hand,  ovulation,  the  discharge  ol 
an  ovum  or  ova,  or  at  any  rate  the  condition  of  the  ovary  associated 
with  this  discharge,  seems  to  be  indispensable.  For  extirpation  of 
the  ovaries  in  a  large  number  of  guinea-pigs  prevented  the  formation 
of  deciduomata  from  wounds  of  the  uterus  made  at  the  most  favour- 
able period  after  copulation.  The  uterus  then  appears  to  have  an 
inherent  power  of  responding  to  such  a  stimulus  as  a  mechanical 
injury  by  the  production  of  a  decidual  structure,  but  only  under  the 
influence  of  the  ovary.  The  ovarian  factor  is  probably  not  nervous 
but  chemical,  some  specific  substance  which  acts  on  the  uterus 
being  liberated  periodically  in  connection  with  the  sexual  rhythm. 

Development  of  the  Ovum. — ^Before  fecundation,  and  apparently 
as  a  preparation  for  it,  the  ovum  is  the  seat  of  remarkable  changes. 


DEVELOPMENT  OF  THE  OVUM  1079 

similar  upon  the  whole  to  those  seen  in  the  mitotic  or  indirect 
division  of  ordinary  cells.*  Tiiey  have  been  most  fully  studied  in 
the  eggs  of  certain  invertebrate  animals. 

The  division  of  the  cell  is  initiated  by  changes  in  the  centrosome  and 
attraction  sphere.  The  centrosome  divides  into  two  daughter  ct-ntro- 
somes.  These  take  up  a  position  one  at  each  pole  of  the  nucleus. 
Each  daughter  centrosome  is  surrounded  by  a  system  of  radiatinjj;  lines 
or  filaments,  which  arc  less  conspicuous  than  the  chromatin  filaments 
of  the  nucleus,  since  they  do  not  stain  as  these  do.  Meanwhile  the 
nuclear  membrane  and  the  nucleoli  disappear,  or  at  any  rate  become 
indistinguishable  from  the  rest  of  the  chromatin  skein.  The  skein 
breaks  up  into  chromosomes,  the  number  of  which  is  constant  for  a  given 
species,  but  is  not  the  same  in  all  species  of  animals. 

The  daughter  centro.somes  or  astrospheres  are  united  by  meridional 
achromatic  fibres,  which  form  a  spindle  running  through  the  nucleus 
from  one  pole  to  the  otlier.  The  chromosomes  arrange  themselves  at 
right  angles  (equatorially)  to  the  spindle,  and  then  each  chromosome 
divides  longitudinally  into  two.  The  halves  of  the  chromosomes  now 
pass  toward  tlieir  respective  centrosomes,  being  perhaps  guided  by  the 
fibres  of  the  spindle.  It  results  from  this  that  two  daughter  nuclei  are 
formed,  each  with  the  same  number  of  chromosomes  as  the  original 
nucleus,  although  with  only  half  the  amount  of  chromatin.  The  cyto- 
plasm divides  also,  so  that  the  parent  cell  is  now  represented  by  two 
daughter  cells.  In  ordinary  cell  division  the  two  daughter  cells  are  of 
equal  size,  but  in  tiie  division  of  the  ovum  which  occurs  before  fertiliza- 
tion the  two  resulting  cells  are  very  unequal.  The  large  cell  continues 
to  be  known  as  the  ovum;  the  small  one  is  the  first  polar  body.  After 
extrusion  of  the  first  polar  body  the  ovum  again  divides  unequally.  A 
new  spindle  forms,  and  a  second  polar  body,  again  much  the  smaller  of 
the  two  daughter  cells,  is  cast  off.  There  is  a  difference,  howevo*. 
between  the  process  of  division  which  gives  rise  to  the  first  and  that 
which  gives  rise  to  the  second  polar  body.  In  the  case  of  the  latter  a 
so-called  rechiction-division  occurs;  the  chromo.somes  do  not  split  longi- 
tudinally, but  half  of  the  original  number  pass  into  each  daughter 
nucleus.  As  to  the  significance  of  these  changes  there  has  been  much 
discussion.  It  is  agreed  that  the  result  of  the  process  is  the  expulsion 
of  a  portion  of  the  chromatin,  the  ovum  now  possessing  only  half  the 
original  number  of  chromosomes,  although  nearly  all  the  original 
cytoplasm.  In  fertilization  the  original  number  is  restored  by  the  male 
element  when  it  arrives  and  penetrates  the  ovum.  For  in  the  final  cell 
division  by  which  the  mature  spermatozoon  is  formed  the  chromosomes 
of  its  nucleus  are  also,  after  two  divisions  essentially  similar  to  those 
occurringin  maturation  of  theovum,  reduced  tohalf  the  normal  number. 

The  two  reduced  nuclei  in  tlie  fertilized  ovum  arc  spoken  of  as  the 
male  and  female  pronuclei.  By  their  union  a  single  nucleus  is  formeil 
with  the  number  of  chromosomes  normal  to  the  species. 

An  enormous  amount  of  interesting  work  has  been  done  witli  the 
view  of  illustrating  the  connection  of  the  complicated  phenomena 
described  with  the  structure  of  the  ovum.  Only  a  bare  reference 
to  one  or  two  of  the  experiments  is  possible  here.  Driesch  and 
Hertwig  find  that  the  nucleus  can  be  made  artificially  to  change  its 
place  with  reference  to  the  yolk,  without  hindering  the  development 
♦  For  figures  illustrating  tlie  chaages,  see  any  gootl  textUmk  ol  Histology. 


io8o  REPRODUCTION 

of  a  normal  animal.  Lillie  has  shown  that  centrifugalization  of  the 
eggs  of  annelids,  although  it  markedly  alters  the  distribution  of  the 
yolk  and  other  substances,  does  not  affect  the  form  of  cleavage. 
The  polar  bodies  appear  in  the  position  which  they  would  normally 
occupy.  In  other  words,  no  redistribution  of  the  granules  or  nucleus 
affects  the  polarity  of  the  egg,  which  therefore  is  a  function  or 
property  of  the  ground  substance  of  the  protoplasm.  The  whole 
of  the  protoplasm,  however,  is  not  necessary  for  complete  develop- 
ment. Even  in  Amphioxus,  the  lowest  of  the  vertebrates,  the 
eggs  have  been  broken  up  by  shaking,  and  a  complete  animal 
evolved  from  as  little  as  one-eighth  of  an  ovum.  If  the  separation 
was  incomplete  a  kind  of  Siamese  twins,  or  even  triplets,  could  be 
obtained  (Wilson  and  Mathews).  Nor  is  it  always  indispensable 
that  both  pronuclei  should  be  present. 

Parthenogenesis. — Attempts  have  been  made  to  separate  the 
constituents  of  spermatozoa  which  are  essential  to  fertilization. 
From  the  sperm  of  a  sea-urchin  a  substance  can  be  extracted  by 
strongly  hypotonic  salt  solutions,  containing  ether,  which  acts  as  a 
powerful  fertilizing,  agglutinating,  and  cytolyzing  agent  upon  the 
eggs.  It  is  soluble  in  dilute  acid,  and  is  probably  identical  with  a 
fertilizing  agent  called  oocytase  present  in  blood-serum  (Robertson). 
Whatever  it  is  that  the  spermatozoon  supplies,  the  process  of 
fertilization  can  in  certain  forms  be  started  artificially  in  the  absence 
of  spermatozoa  or  any  of  their  constituents.  The  studies  of  Loeb 
and  his  pupils  on  artificially  induced  parthenogenesis  are  of  special 
importance.  When  the  unfertilized  eggs  of  the  sea-urchin  are 
exposed  for  one  or  two  minutes  to  50  c.c.  of  sea-water,  to  which 
3  or  4  c.c.  of  decinormal  acetic  acid  has  been  added,  the  majority  of 
the  eggs  form  the  membrane  characteristic  of  the  entrance  of  the 
spermatozoon.  When  these  eggs  are  afterwards  exposed  for  thirty 
to  forty  minutes  to  100  c.c.  of  sea-water,  to  which  14  or  15  c.c.  of  a 
strong  solution  of  sodium  chloride  (two  and  a  half  times  the  strength 
of  a  normal  solution,  or  about  14-6  per  cent.)  has  been  added,  those 
of  the  eggs  which  have  formed  membranes  develop  into  swimming 
larvas  that  rise  to  the  surface.  These  larvas  develop  into  perfect 
sea-urchin  larvas  or  '  plutei  '  as  fast  as  the  larvas  of  eggs  fertilized 
with  sperm. 

The  facts  of  parthenogenesis  show  that  it  is  not  absolutely  neces- 
sary for  development  that  the  ovum  should  have  the  normal  number 
of  chromosomes  restored.  It  can  develop  with  half  the  number,  the 
chromosomes  of  the  female  pronucleus  being  sufficient  for  growth, 
although,  of  course,  in  this  case  for  a  growth  uninfluenced  by  the 
properties  of  the  male  element.  In  like  manner  it  is  stated  that 
portions  of  the  maturated  ovum  devoid  of  a  nucleus  can  undergo 
development  if  penetrated  by  a  spermatozoon,  the  chromosomes  of 
the  male  pronucleus  being  sufficient  for  growth. 


FORMATION  OF  THE  hMDRYO  lo«i 

Formation  of  the  Embryo. ^ — Not  till  all  these  events  have  taken  place 
— extrusion  of  the  two  polar  bo<iics,  or  maturation  ;  ix-nctration  of  the 
spermatozoon,  and  blending  of  its  head  (llie  male  pronucleus)  with  the 
remnant  of  the  nucleus  of  the  (num  (female  pronucleus),  or  fecundation 
— not  till  then  docs  the  ovum  begin  the  prcKcss  of  repeated  <li vision  by 
which  the  wliole  body  is  reproduced,  'ihe  fused  or  segmentation  nucleus 
divides  into  two,  each  containing  the  normal  numlx.'r  of  chronnjscimes 
derived  from  the  splitting  of  those  contributed  by  both  the  male  and 
female  elements.  It  is  believed  that  tlie  division  takes  plate  in  such  a 
way  that  both  male  and  female  chromosomes  are  represented  in  each 
nucleus.  The  cytoplasm  being  also  cleft  by  a  corresponduig  furrow, 
two  complete  nucleated  cells  make  their  apj)earance.  These  divide  in 
turn,  till  at  length  (in  the  mammal)  the  embryo  is  represented  by  a 
hollow  sphere  or  vesicle,  with  a  cellular  crust.  During  division  the 
upper  or  outer  cells  have  always  Ix-en  larger  than  the  inner  and  lower, 
and  have  multiplied  more  rapidly;  and  tlius  it  comes  about  that  the 
hollow  sphere  of  large  cells  encloses  a  mass  of  smaller  cells,  along  with 
remnants  of  broken-down  yolk  and  of  fiuid  derived  by  absorption  from 
the  contents  of  the  uterus.  The  smaller  cells  continue  to  multiply  an<l 
arrange  themselves  as  a  lining  to  the  sphere  already  formed,  so  that  in  a 
short  time  it  becomes  double,  and  we  have  already  differentiated  two  of 
the  primary  embryonic  layers — the  ectoderm,  also  called  the  epiblast,  or 
superficial,  and  the  endodcrm,  also  called  the  hypoblast,  or  deep  layer. 
The  whole  sphere  is  called  tlie  blastoderm,  or  the  blastodermic  vesicle. 

Willie  this  inner  shell  of  endodermic  cells  is  gradually  creeping  on  to 
completion,  there  appears  at  a  part  where  it  is  already  fully  formed  a 
small  opaque  whitish  disc,  the  germinal  area  or  embryonal  shield.  This 
represents  the  stocks  on  which  tlic  framework  of  the  embryo  is  to  be  laitl 
down.  The  area  elongates;  at  its  posterior  end  appears  a  thickened 
line,  the  primitive  streak,  soon  furrowed  by  a  longitudinal  groove,  the 
primitive  groove,  that  marks  the  direction  in  which  the  long  axis  of  the 
future  embryo  will  lie,  but  is  not  itself  a  permanent  line  in  the  building, 
and  ultimately  vanishes.  The  appearance  of  the  primitive  streak  is  the 
signal  that  a  rapid  proliferation  of  the  cells  of  the  gernnnal  area,  and 
especially  of  the  ectCKlerm,  has  begun  ;  and  this  goes  on  until  a  third  layer 
is  formed,  intermediate  in  position  to  the  original  two.  and  therefore 
named  the  mesoderm.  While  this  is  pushing  its  way  over  the  germinal 
area  and  into  the  rest  of  the  blastodermic  vesicle,  the  ectoderm  in  front 
of  the  primitive  streak  rises  up  in  two  lateral  ridges,  enclosing  between 
them  the  medullary  groove.  The  medullary  groove  is  the  begiiming  of 
the  cerebro-spinal  axis:  its  walls  first  come  to  overhang  tlie  furrow,  and 
then  to  coalesce;  and  the  medullary  groove  has  now  become  the  neural 
canal.  Immediately  under  it  the  mesoderm  forms  a  rod  of  cells,  the 
notochord,  which  is  the  forerunner  of  the  vertebral  column;  around  this 
the  bodies  of  the  vertebra'  are  afterwards  developed  from  cubical  masses 
of  mesodermic  cells,  arranged  in  pairs  along  the  notochord.  and  called 
the  protovertebrce.  The  rest  of  the  mesoderm,  running  out  on  each  side 
from  the  protovertebra?,  splits  into  two  layers,  an  upper  or  somatic  layer. 
which  unites  with  the  ectoderm,  forming  with  it  the  somatopleure.  and 
a  lower  or  splanchnic  layer,  which  unites  with  the  endtxlcrm  to  form 
the  splanchnopleure.  Between  the  soinatoi)leure  and  the  splanchnt>- 
pleurc  is  a  space  called  the  ccclom,  or  pleuro-pciitoneal  cavity  (Fig.  462). 
The  layer  of  ectoderm  which  envelops  the  whole  (termeil  the  tropho- 
blast,  from  its  nutritive  function),  in  conjunction  with  tiie  underlying 
mesoderm,  represents  the  prechorion.  the  early  stage  of  the  chorion 

Up  to  the  jiresent,  apart  from  the  eiu  losiire  of  the  neural  canal,  all  this 
formative  activity  is  buried  U-msUii  the  surface  ol  ilw  hIastiKlcrm,  and 


Xo82  REPRODUCTION 

has  not  showed  itself  by  any  external  token  ;  the  embryo  still  appears  as 
a  portion  of  the  germi  al  area,  and  lies  in  its  plane.  But  now  a  pocket, 
or  crease,  or  moat,  beginning  at  the  head  as  the  head-fold,  then  pushing 
under  the  tail,  gradually  creeps  round  and  undermines  the  whole 
embiyo,  which  is  laised  above  the  general  level,  and,  as  it  were,  scooped 
out  from  the  rest  of  the  blastoderm;  till  at  length  it  lies  on  the  latter, 
something  like  an  upturned  canoe,  enclosing  a  tube,  complete  in  front 
and  behind,  but  still  open  in  the  middle,  where  it  communicates  with 
the  interior  of  the  yolk-vesicle.  Since  this  tube  has  been  formed  by  the 
tucking  in  of  the  three  ancestral  layers  of  the  blastoderm,  it  follows  that 
it  is  lined  by  endoderm,  supported  externally  by  the  splanchnic  sheet 
of  mesoderm.  So  that  now  the  body  consists  of  a  dorsal  tube  (the 
neural  canal),  essentially  of  ectodermic  origin,  a  ventral  tube  (the 
alimentary  canal),  essentiall^'^  of  endodermic  origin,  and  between  the 
two  a  massive  double  layer  of  mesodermic  tissue,  which  contributes 
supporting  elements  to  both.  At  this  point  it  may  be  well  to  emphasize 
the  fact  that  this  embryological  distinction  of  the  three  primitive  layers 
has  a  deep  and  fundamental  meaning,  and  corresponds  to  a  physiological 
distinction  that  endures  throughout  life.  The  endoderm,  the  lowest 
layer  in  position,  may  also  be  described  as  the  lowest  in  the  physiological 
hierarchy.  It  furnishes  the  epithelial  lining  of  the  alimentary  canal 
from  the  beginning  of  the  oesophagus  to  near  the  end  of  the  rectum,  as 
well  as  the  epithelium  of  the  organs  which  arise  from  diverticula  of  the 
primitive  intestine — viz.,  the  digestive  glands  (with  the  exception  of  the 
salivary  glands),  the  lungs,  and  the  passages  leading  to  them,  the 
thyroid,  and  the  greater  part  of  the  thymus  gland  in  its  primitive  con- 
dition before  the  lymphoid  tissue  derived  from  the  mesoderm  has  as 
yet  grown  into  it.  According  to  some  authorities,  the  notochord  is  also 
derived  from  the  endoderm. 

Upon  the  whole,  it  may  be  said  that  the  tissues  of  endodermic 
origin  are  essentially  concerned  in  chemical  labours,  in  the  absorption 
of  food  material  and  excretion  of  waste  products.  The  mesodermic 
tissues  are  essentially  concerned  in  mechanical  labour;  they  are  the 
tissues  of  movement  and  of  passive  support.  The  ectodermic  tissues 
are  at  the  top  of  the  p^'^ramid ;  they  govern  the  rest. 

From  the  mesoderm  arise  the  muscles,  the  entire  vascular  system, 
with  its  blood-  and  lymph -corpuscles,  the  bones  and  connective  tissues; 
and  the  Wolffian  body  and  its  appendages,  which  are  the  predecessors 
of  the  genital  glands  and  ducts,  and  of  the  chief  portion  of  the  renal 
apparatus. 

The  ectoderm  forms  the  epidermis  and  its  appendages,  the  epithelial 
end-organs  of  the  nerves  of  special  sense,  and  the  nervous  system, 
cerebro-spinal  and  sympathetic.  The  salivary  glands  and  the  mucous 
lining  of  the  mouth  and  anus  are  developed  from  the  ectoderm,  which 
is  indented  to  meet  the  intestinal  canal  and  give  it  access  to  the  exterior 
at  either  end. 

It  is  not  possible  here  to  trace  in  detail  the  development  of  all  the 
organs  of  the  embryo.  Its  nutrition  and  metabolism  not  only  dis- 
tinctly belong  to  the  physiological  domain,  but,  carried  on  as  they  are 
under  conditions  that  seem  so  strange,  and  even  so  bizarre,  to  one 
acquainted  only  with  adult  physiology,  are  calculated  to  throw  light 
on  the  metabolic  processes  of  the  fully-developed  body.  And  they 
cannot  be  understood  without  reference  to  the  peculiarities  of  the 
vascular  system  in  foetal  life.  These  we  shall  accordingly  describe,  but 
for  further  details  as  to  the  anatomy  of  the  embryo  the  student  is 
referred  to  some  standard  anatomical  textbook,  such  as  Quain's 
'  Anatomy.' 


FORMATION  OF  THE  EMBRYO 


1083 


Development  of  the  Connections  between  the  Embryo  and  the 
Uterus. — In  the  first  period  of  its  development  the  ovum,  nestling  in 
the  pouch  formed  by  the  decidua  serotina  and  reficxa,  is  fed  from  the 
maternal  blood  and  tissues  directly,  without  the  mediation  of  foetal 
bloodvessels,  through  the  finger-like  processes  or  villi  with  which  its 
external  layer,  the  zona  pcllucida,  becomes  studded.  At  the  earliest 
stage  at  which  a  human  ovum  has  been  studied  after  implantation  it  is 
already  enveloped  by  a  thick  ectodermic  covering  (the  troj)h<>blastic 
envelope),  consisting  of  two  lavcrs  of  cells,  one  unquestionably  of  foetal 
origin,  the  so-called  cells  of  Langhans,  and  the  other  the  sx-ncytium,  the 
origin  of  which  is  assigned  by  some  authorities  to  the  ovum,  by  otlicrs 
to  the  maternal  tissues.  The  trophoblastic  covering  is  everywhere  in 
contact  with  the  maternal  blood,  which,  pushing  its  way  into  the  tropho- 
blast  at  intervals,  divides  it  into  columns.  Later  on  the  foetal  mesoderm 
grows  into  these,  and  so  the  primary  chorionic  villi  arc  formed.  It  is 
not  till  after  the  first  three  weeks  that  blofxl vessels  make  their  way  into 
these  villi,  although  the  mesoderm  of  the  fcutus  begins  to  enter  the  villi 
about  the  end  of  the  first,  or  the  beginning  of  the  second,  week.  The 
scanty  yolk  of  the  human 


line  of  union 

.prechorion 
■  embryo 
■  amnion 


somatopleure 
coelom 

splanchnopleure 


ovTjm  IS  totally  inade- 
quate to  supply  it  with 
nutriment  for  the  time 
that  elapses  before  the 
bloodvessels  are  devel- 
oped, and  food  sub- 
stances must  be  obtained 
from  the  maternal  liquids 
bv  imbibition,  osmosis, 
diffusion,  or  filtration, 
aided,  perhaps,  by  more 
special  absorptive  pro- 
cesses on  the  part  of  the 
foetal  tissues.  Soon  the 
heart  appears  as  a  tube 
(at  first  double),  formed 
by  cells  belonging  to  the 
splanchnic  layer  of  the 
mesoderm.  It  begins  t^ 
pulsate  in  the  chick  as 
early  as  the  middle  of  the 
secondday,  although  it  as  ,       rt.  i 

yet  contains  neither  nerve-cells  nor  fully-formed  muscular  fibres,  in 
the  mammal  pulsation  is  late  in  making  its  appearance,  m  man  about 
the  beginning  of  tlie  third  week.  A  bloodvessel  grows  out  from  th« 
anterior  end  of  the  heart  and  divides  into  two  primitive  aortic  arches, 
from  each  of  which  a  vessel  (omphalomesenteric  cr  vitelline  artery)  runs 
out  in  the  mesoderm  covering  the  umbilical  vesicle,  or  yolk-sac.  The 
blood  is  returned  to  the  heart  bv  the  vitelline  veins  coursing  m  on  the 
walls  of  the  vitelline  duct.  In  this  wav  the  store  of  nutriment  m  the 
umbUical  vesicle  of  the  chick,  which  is  the  only  solid  or  liquid  fooci  it 
receives  or  needs  during  the  whole  jK-riod  of  development,  is  tapix-d. 
and  a  regular  channel  of  supply  established.  Oxygen  is  at  the  same 
time  absorbed  through  the  porous  shell;  but  later  on  this  respiratory 
function  is  taken  over  by  the  second  or  allantoic  circulation.  In  the 
mammal  the  circulation  on  the  umbilical  vesicle  is  of  much  less  consc- 
nuence  for  the  quantity  of  material  left  over  after  the  formation  of  the 
blastoderm  is  exceedingly  small;  it  is  only  with  a  few  days'  provision 
in  its  haversack  that  the  embryo  starts  out  on  its  developmental  march 


Fig.  461.— Sliowiiig  the  Folds  of  the  Somatopleure 
in  a  Bird's  0\'ura  uniting  over  the  Embryo 
and  beojining  dL-marcated  into  Amnion  and 
Prechorion  (Keith). 


1084 


REPRODUCTION 


And  the  vitelline  vessels  deriving  their  further  supply  of  food  and 
oxygen  from  the  tissues  of  the  mother  in  contact  with  tiie  ovum  cease 
to  be  of  use  as  soon  as  the  second  and  more  perfect  placental  circulation 
is  established,  and  soon  shrivel  up  and  disappear,  as  the  umbilical 
vesicle  shrinks. 

The  second  circulation  of  the  embryo  is  developed  in  connection  with 
a  remarkable  offshoot  from  the  hind-gut  called  the  allantois,  which, 
before  the  fifth  day  in  the  chick  and  during  the  second  week  in  man, 
pushes  its  way  out  between  the  somatic  and  splanchnic  layers  of  the 
mesoderm — i.e.,  in  the  pleuro-peritoneal  cavity — and  grows  through  the 
umbilicus,  carrying  bloodvessels  along  with  it  in  its  mesodermic  layer. 
Still  earlier,  and,  indeed,  while  the  embryo  is  bein  ;;  separated  off  from 

and  raised  above 
the  level  of  the  rest 
of  the  blastoderm 
by  the  deepening 
of  the  ditch  around 
it,  the  further 
banks  of  this  fur- 
row, formed  of 
ectoderm  and 
somatic  mesoderm, 
have  risen  up  on 
every  side,  and, 
growing  over  the 
back  of  the  em- 
bryo, have  finally 
coalesced  and  en- 
closed it  in  a 
double-  walle  d 
pouch  (Fig.  462). 
The  superficial 
layer  of  the  pouch 
is  called  the  false 
amnion ;  it  soon 
blends  with  the 
tufted  chorion  or 
common  outer 
envelope  of  the 
ovum.  The  inner 
layer  persists  as 
the  true  amnion  ;  a 
liquid,  the  amniotic 
■fluid,  is  secreted  in  the  cavity  which  it  encloses;  and  the  embryo,  loosely 
anchored  for  the  rest  of  its  intra-uterine  life  by  the  umbilical  cord  alone, 
floats  freely  within  it.  The  amniotic  fluid  acts  as  a  water-jacket  or 
cushion,  to  break  the  force  of  the  inevitable  shocks  and  jars  transmitted 
from  the  mother  to  the  foetus  and  from  the  foetus  to  the  mother.  To 
some  extent,  in  addition,  it  may  serve  as  a  nutritive  fluid,  for  substances 
can  pass  from  the  blood  of  the  mother  into  the  amniotic  fluid,  and  the 
amniotic  fluid  can  be  swallowed  by  the  foetus.  This  is  shown  by  the 
fact  that  sodium  sulphindigotate,  when  injected  into  the  maternal 
circulation,  is  found  in  the  amniotic  fluid  and  in  the  alimentary  canal 
of  the  foetus,  although  not  in  any  of  the  foetal  tissues.  Fine  lanugo 
hairs  from  the  foetal  skin  have  also  been  found  in  the  meconium. 

The  precise  origin  and  manner  of  formation  of  the  amniotic  fluid 
have  not  been  settled.     It  is  probably  in  the  main  a  maternal  secretion 


Fig.  462. — Diagram  to  illustrate  Formation  of  Amnion  and 
Allantois.  A,  cavity  of  true  amnion;  F,  F'.  folds  about 
to  coalesce  and  complete  the  amniotic  cavity;  m,  meso- 
dermic layer  of  amnion;  B,  allantois;  I,  intestinal  cavity 
of  embryo;  Y,  yolk-sac;  h,  endodermic  layer;  e,  ecto- 
dermic  layer  of  embryo.  The  embryo  is  the  shaded  por- 
tion in  the  middle  of  the  figure.  E  is  placed  over  the 
head  region.  No  attempt  is  made  to  delineate  its  actual 
form.  The  mesoderm  is  represented  by  the  interrupted 
line. 


NUTIUriON  OF  THE  EMBRYO  1083 

or  transudation.  But  something  is  coutributed  by  tlie  foetus  in  the 
form  of  renal,  and  perhaps  of  skin,  secretions.  I  he  fluid  is  poor  in 
sohds.  Its  maximum  content  of  protein,  reached  (hiring  the  first  half 
of  pregnancy,  is  only  0-7  per  cent.  I^tcr  on  it  diminishes,  and  at  full 
term  is  only  one-tenth  of  this  amount.  The  specific  gravity  is  1006  to 
1009.  Its  osmotic  concentration,  as  measured  by  the  depression  of  the 
freezing-point,  is  less  than  that  of  the  mother's  blood-scrum. 

The  allantois,  growing  out  at  the  umbilicus,  in  the  manner  described, 
insinuates  itself  between  tlie  true  and  false  amnion,  and  so<jn  blends 
with  the  latter.  For  a  time  the  secretion  of  the  primitive  kidneys 
continues  to  be  poured  into  the  cavity  of  the  allantois,  so  that  it  serves 
in  part  as  an  excretory  organ,  while  in  the  bird  it  also  performs  the 
function  of  respiration  ;  and  in  the  mammal  botii  food  and  oxygon  arc 
carried  by  its  vessels  to  the  frctus  during  the  greater  jjart  of  intra- 
uterine life.  But  later  on  the  outgrowth  atroj:)hics  and  disappears,  all 
except  its  origin  from  the  alimentary  canal,  whicli  dilates  and  jK-rsists 
as  the  urinary  bladder,  and  its  bloodvessels,  which  grow  in  the  form  of 
tufts  or  loops  into  the  chorionic  villi.  The  vessels  are  fed  by  two 
umbilical  arteries  which  arise  from  the  hypogastric  arteries  and  run  out 
at  the  umbilicus  on  tlie  allantois.  The  blood  is  returned  by  an  umbilical 
vein,  whose  further  course  we  shall  have  soon  to  trace.  The  shrivelled 
stalk  of  the  allantois,  projecting  through  the  umbilicus,  takes  part,  \v\^^\ 
its  bloodvessels,  in  the  formation  of  the  umbilical  cord,  which  contains 
also  the  remains  of  the  yolk-sac  and  is  clothed  externally  by  a  layer  of 
the  amnion.  Continuous  with  the  umbilical  cord,  and  stretching  from 
the  umbilicus  to  the  urinary  bladder,  is  a  portion  of  the  allantois  which 
is  represented  in  extra-uterine  life  by  a  thin  cord-like  structure,  the 
urachus.  The  vascular  tufts  of  the  chorion,  which  at  first  cover  tlie 
whole  surface  of  the  ovum  and  suck  up  food  and  oxygen  from  decidua 
serotina  and  rcflexa  alike,  disappear  in  the  region  of  the  reflexa,  hyper- 
trophy all  over  the  serotina — that  is,  where  the  o\-um  is  in  actual  contact 
witn  the  uterine  wall — and  this  part  of  the  chorion  is  now  distinguished 
ad  the  chorion  frondosum.  The  giant  villi  of  tlie  chorion  frondosum 
push  their  way  into  the  thickened  decidua  serotina,  and  ultimately 
penetrate  into  the  great  capillaries  or  sinuses  of  tlie  uterine  mucous 
membrane.  At  the  same  time  the  tissue  of  the  villi  external  to  the 
vessels  becomes  reduced  to  a  mere  film,  so  that,  except  for  a  thin  cover- 
ing of  decidual  cells,  the  fcetal  vessels  are  bathed  in  maternal  blood. 
By  this  interweaving  of  decidua  and  chorion  frondosum  is  formed  the 
placenta,  which  for  the  rest  of  intra-uterine  life  acts  as  the  great 
respiratory,  alimentary,  and  excretory  organ  of  the  foetus. 

Exchange  of  Materials  in  the  Placenta. — ^The  maternal  blood,  as 
it  streams  through  tlic  colossal  capillaries  of  the  decidua,  gives  up 
to  the  foetal  blood  oxygen  and  food  substances  and  receives  from  it 
carbon  dioxide  and  in  all  probability  urea.  It  is  true  that  the  blood 
in  the  uterine  sinuses  is  not  itself  fully  oxygenated;  it  is  ni)t  bright 
red  arterial  blood.  But  it  yet  contains  more  oxygen,  and  oxygen  at 
a  higher  partial  pressure  (p.  246).  than  the  purest  blood  of  the  foetus, 
and  is,  therefore,  able  to  part  with  some  of  the  surplus  to  the  dark 
stream  of  oxygen-impoverished  blood  brought  by  the  umbilical 
arteries  to  the  placenta.  Thus,  it  has  been  found  that  while  the 
blood  of  the  umbilical  artery  of  the  fcctus  of  a  sheep  had  47  volume^ 
per  cent,  of  carbon  dioxide,  and  only  23  of  oxygen,  that  of  the 


io86  REPRODUCTION 

umbilical  veins  had  6*3  volumes  of  oxygen,  and  only  40-5  of  carbon 
dioxide  (Zuntz  and  Cohnstein).  In  the  exchange  of  gases  between 
the  placental  and  the  foetal  blood  the  same  general  features  present 
themselves  as  in  the  external  and  internal  respiration  of  the  mother, 
with  this  difference,  that  the  exchange  of  oxygen  is  neither  between 
air  and  haemoglobin,  as  in  the  lungs,  nor  between  haemoglobin  and 
tissue  elements,  as  in  the  organs;  but  between  maternal  and  foetal 
haemoglobin,  of  course,  through  the  mediation  of  the  maternal  and 
foetal  plasma.  There  is  no  reason  to  suppose  that  the  mechanism 
of  the  exchange  is  essentially  different  from  that  of  the  more  familiar 
forms  of  respiration.  Diffusion  of  the  gases  from  places  of  higher 
to  places  of  lower  tension  unquestionably  plays  an  important 
part.  But  this  does  not  exclude  the  possibility  of  a  more  active 
process  of  some  other  kind,  although  there  is  at  present  no  direct 
evidence  of  such  a  gaseous  secretion  as  has  been  previously  discussed 
in  connection  with  pulmonary  respiration  (p.  260).  The  presence  of 
oxydases  in  the  placenta  does  not  throw  any  light  on  the  question. 
For  there  is  no  proof  that  they  act  in  transferring  oxygen  from  the 
one  circulation  to  the  other,  and  oxydases  are  found  in  the  most 
diverse  tissues.  Their  significance  for  the  combustion  processes  of 
the  body  has  already  been  alluded  to  (p.  267). 

Salts  soluble  in  water,  including  not  only  those  necessary  for 
nutrition,  like  sodium  chloride,  but  many  foreign  salts,  pass  readily 
from  the  placenta  to  the  foetus,  and  in  general  more  easily  the  lower 
their  molecular  weight.  Such  salts  as  potassium  iodide,  e.g.,  when 
injected  into  the  maternal  circulation,  appear  in  the  foetus  in  a  very 
short  time.  On  the  other  hand,  colloidal  solutions — e.g.,  of  silver 
or  silicic  acid — do  not  pass  over  at  all.  It  is  of  practical  importance 
that  substances  like  chloroform,  ether,  and  other  narcotics,  and  alka- 
loids like  morphine  and  scopolamine,  when  administered  in  obstetrical 
practice,  may  find  their  way  from  the  mother  to  the  child,  although 
more  slowly  and  more  capriciously  than  the  salts.  While  diffusion 
and  osmosis  assuredly  take  part  in  the  passage  of  materials  from  the 
placenta  to  the  foetus,  there  is  no  more  reason  to  conclude  that  the 
whole  exchange,  even  for  the  salts,  depends  upon  such  simple  physical 
processes  than  there  is  in  the  case  of  the  exchange  between  any  one 
of  the  maternal  tissues  and  the  maternal  blood.  The  essential 
similarity  of  placental  and  intestinal  absorption,  to  take  one  instance, 
is  seen  in  the  mechanism  by  which  the  foetus  gains  the  iron  required 
for  the  development  of  its  haemoglobin.  The  haemoglobin  of  the 
mother  appears  to  be  the  most  important  source  of  this  iron. 
Erythrocytes  in  all  stages  of  decomposition  can  be  found  in  con- 
tact with  the  chorionic  villi,  and  even  in  the  epithelium  covering 
the  villi.  These  corpuscles  come  partly  from  extravasations  in 
the  maternal  portion  of  the  placenta,  but  it  is  possible  that  the 
villi  also  possess  the  power  of  haemolyzing  intact  corpuscles  in  the 


NUTRITION  OF  THE  EMBRYO  1087 

circulating  placental  blood.  Iron  can  be  demonstrated  by  micro- 
chemical  reactions  in  the  epithelial  cells  of  the  chorionic  villi  as  fine 
granules,  which  increase  in  size  towa  ds  the  base  of  the  cells.  As  we 
pass  deeper  into  the  villus  towards  its  central  bloodvessel,  the 
granules  again  diminish  in  siae.  The  picture  is  very  like  that  seen 
in  the  absorption  of  iron  from  the  intestine.  And  if  the  micro- 
chemical  picture  is  practically  the  same,  the  process  by  which  the 
iron  is  absorbed  is  not  likely  to  be  fundamentally  different  in  the 
two  cases  (p.  440). 

The  same  is  true  of  the  passage  of  fat  across  the  placenta.  Fat 
can  always  be  demonstrated  microchemically  in  the  chorionic  villi 
The  most  superficial  layer  of  the  villi  is  free  from  visible  fat  droplets. 
They  increase  in  number  towards  the  base  of  the  epithelial  cells. 
As  in  the  case  of  the  intestine,  these  appearances  agree  well  with 
the  view  that  the  fat  is  split  before  being  absorbed  by  the  villi,  and 
undergoes  resynthesis  in  the  epithelium.  That,  as  a  matter  of  fact, 
fat  passes  from  the  mother  to  the  fcetus  is  shown  by  the  observ'ation 
that  when  pregnant  guinea-pigs  were  fed  with  a  foreign  fat  (from 
cocoanuts),  the  characteristic  fatty  acid  (lauric  acid)  was  found  in 
the  foetus.  This,  however,  does  not  exclude  the  possibility  that  the 
foetus  may  form  fat  in  its  own  tissues  from  carbo-hydrates,  and 
perhaps  from  proteins,  as  it  is  destined  to  do  in  extra-uterine  life. 

Among  the  carbo-hydrates  the  passage  of  dextrose  from  the 
maternal  to  the  foetal  blood  has  been  experimentally  demonstrated 
A  specially  interesting  proof  is  afforded  in  cases  where  the  mother 
suffers  from  diabetes  mellitus.  In  one  case  in  which  the  mother, 
during  diabetic  coma,  was  delivered  of  a  stillborn  child,  the  blood 
of  the  child  contained  22  per  cent,  of  sugar,  its  urine  524  per  cent., 
and  the  amniotic  fluid  047  per  cent.  The  blood  of  the  mother  had 
a  sugar  content  of  08  per  cent.,  and  her  urine  a  content  of  694  per 
cent.  The  sugar  of  the  maternal  blood  is  not  the  only  source  of  the 
carbo-hydrates  of  the  foetus.  The  glycogen  store  of  the  placenta  is 
to  be  regarded  as  a  second  source,  which  is  rendered  available  on 
conversion  into  dextrose  by  the  placental  diastatic  ferment.  This 
store  of  easily  available  food  material  is  especially  important  in  the 
early  stages  of  development  of  the  ovum  before  a  circulation  has 
been  established  in  the  villi.  In  the  youngest  ova  investigated  the 
decidual  covering  has  been  found  rich  in  glycogen. 

While  it  is  to  be  supposed  that  the  products  of  the  hydrolytic 
decomposition  of  proteins  can  be  absorbed  by  the  foetal  blood  in  its 
passage  through  the  placenta,  to  be  synthesized  to  the  appropriate 
tissue  proteins  in  the  foetal  organs,  there  is  evidence  that  certain 
proteins  can  be  taken  up  without  change.  In  this  connection  it 
must  be  remembered  that  the  mother  is  much  more  cU^ely  related 
to  the  foetus  as  regards  her  protein  composition  than  any  ordinary 
protein  food  can  be  to  an  animal  in  extra-uterine  life.     In  some 


I088  REPRODUCTION 

respects,  indeed,  the  foetus  may  be  considered,  especially,  perhaps, 
in  the  first  stages  of  its  development,  as  a  part  of  the  mother,  an 
additional,  although  very  complex,  organ  rather  than  an  independent 
organism. 

The  blood  of  the  umbilical  artery,  although  far  from  the  level  of 
the  ordinary  arterial  blood  of  the  mother  as  regards  its  gaseous 
content,  is  yet  the  best  the  foetus  ever  gets;  and  by  a  series  of  con- 
trivances it  is  assured  that  this  best  should  go  first  to  the  most 
important  parts — the  liver,  the  heart,  and  the  head — ^while  the  legs 
and  most  of  the  abdominal  organs  have  to  put  up  with  an  inferior 
supply.  This  is  brought  about  mainly  by  the  existence  of  three 
short-cuts  for  the  blood,  which  disappear  in  the  adult  circulation,  the 
ductus  venosus,  the  ductus  arteriosus,  and  the  foramen  ovale. 

The  blood  of  the  umbilical  vein,  rich  in  oxygen  for  foetal  blood, 
passes  partly  through  the  circulation  of  the  liver,  but  a  part  takes 
the  route  of  the  ductus  venosus,  and  empties  itself  into  the  inferior 
vena  cava.  The  latter  gathers  up  the  more  or  less  vitiated  blood 
from  the  inferior  extremities  and  the  renal  and  hepatic  veins,  and 
pours  its  mixed,  but  still  fairly  oxygenated,  contents  into  the  right 
auricle.  By  means  of  the  Eustachian  valve,  the  jet  coming  from 
the  mouth  of  the  inferior  vena  cava  is  directed  into  the  left  auricle 
through  the  foramen  ovale  in  the  inter-auricular  septum.  There 
it  is  joined  by  the  trickle  of  blood  which  is  creeping  through  the 
unexpanded  lungs.  The  left  ventricle  propels  its  contents  through 
the  aorta,  and  thus  a  large  part  of  this  comparatively  pure  or 
second-best  blood  is  sent  to  the  head  and  upper  extremities.  It 
returns  in  a  vitiated  state  by  the  superior  vena  cava  into  the  right 
auricle,  and  owing  to  the  position  of  the  Eustachian  valve  and  the 
direction  of  the  current,  it  flows  now,  not  through  the  foramen  ovale, 
but  into  the  right  ventricle.  Thence  it  is  driven  through  the  pul- 
monary artery,  but  only  a  small  quantity  of  it  finds  its  way  through 
the  lungs;  the  main  stream  is  short-circuited  through  the  ductus 
arteriosus,  and  mingles  with  the  contents  of  the  thoracic  aorta 
below  the  origin  of  the  cephalic  and  brachial  vessels. 

We  may  now  give  something  more  of  precision  to  the  statements 
that  different  parts  of  the  body  receive  blood  of  different  quality; 
and  it  is  possible  roughly  to  divide  the  organs  in  this  respect  into 
four  categories:  (i)  The  liver,  which  partakes  both  of  the  best  and 
the  worst,  the  purified  blood  of  the  umbilical  veins  and  the  vitiated 
blood  of  the  intestines  and  spleen;  (2)  the  heart,  head,  and  upper 
limbs,  which  receive  the  blood  from  the  inferior  extremities  and 
kidneys,  mixed  with  the  pure  blood  of  the  venous  duct;  (3)  the 
legs,  trunk,  intestines,  and  kidneys,  which  are  fed  chiefly  by  the 
off-scourings  of  the  cephalic  end,  mitigated,  however,  by  a  pro- 
portion of  mixed  blood  from  the  inferior  cava;  (4)  the  lungs,  which 
receive  only  a  feeble  stream  of  unmixed  venous  blood. 


NUTRITION  Of  THL  EMliKYO  1089 

These  peculiarities  oi  the  embryonic  circulation  are  in  obvious 
correspondence  with  the  physiological  events  taking  place  in  the 
foetal  body.  The  liver  is  not  only  the  greatest  gland  in  the  embryo, 
as  it  continues  to  be  in  thr  adult,  but  its  activity  seems  to  dwari 
that  of  all  the  other  glands  put  togt-thcr,  and  is  in  strikinj,;  contrast 
with  the  functional  torpor  of  the  lungs.  From  the  thinl  month  of 
intra-uterine  life  the  secretion  of  bile  begins  and  the  intestines 
gradually  till  with  meconium,  of  which  the  principal  constituent  is 
bile.  Accordingly  the  liver  is  most  lavishly  supplied  with  blood, 
while  the  lungs  are  stinted.  And  since  the  liver  has,  as  we  have 
already  learnt,  other  and,  in  the  adult  at  least,  even  more  important 
labours  than  excretion,  a  large  portion  of  the  blood  it  receives 
is  of  the  best  quality:  it  enters  the  gland  comparatively  rich  in 
oxygen,  and  passes  out  comparatively  poor;  while  the  lungs,  which 
have  to  be  nourished  only  for  their  own  sake,  and  are  of  no  use 
whatever  till  the  child  is  born  and  respiration  has  begun,  must  be 
content  with  the  poorest  fare — ^with  the  crumbs  that  fall  from  the 
table  of  fictal  nutrition.  The  full-fed  cephalic  end  of  the  embryo 
grows  far  more  rapidly  than  the  half-starved  inferior  extremities, 
and  the  head  of  the  new-born  child  is  large  in. proportion  to  the  rest 
of  the  botly. 

Metabolism  of  the  Embryo. — There  are  some  other  points  in  the 
physiology  of  intra-uterine  life  which  call  for  remark;  and,  to  sum 
up  in  a  few  words  the  grand  distinction  between  foetal  and  adult 
life,  we  may  say  that  growth  is  the  keynote  of  the  former,  work 
(functional  activity)  of  the  latter.  Thus,  the  muscles  at  an  early 
period  in  their  development,  long  before  any  glycogen  can  be 
found  in  the  liver,  become  the  seat  of  an  accumulation  of  glycogen, 
which,  since  it  cannot  be  used  up  in  contraction  as  in  the  adult 
muscles,  seems  to  be  intimately  connected  with  their  own  growth, 
and  perhaps  also  with  the  growth  of  other  tissues.  It  is  true 
that  the  foetal  tissues  as  a  whole,  including  the  muscles,  are  not 
richer,  as  used  to  be  taught,  but  poorer  in  glycogen  than  adult 
tissues,  and  therefore  the  old  doctrine  that  the  foetal  glycogen  fulfils 
a  special  '  formative  '  function  in  the  development  of  the  tissues, 
has  lost  its  experimental  basis.  Nevertheless,  there  is  a  paral- 
lelism between  the  growth  of  the  foetus  and  its  glycogen  content. 
In  cases  where  the  growth  of  the  foetus  has  been  S|)ontaneously 
arrested,  the  percentage  amount  of  glycogen  in  its  organs  has  been 
found  to  be  diminished  out  of  projwrtion  to  the  diminution  in  weight. 
A  similar  retardation  of  development  can  be  produced  by  repeatedly 
injecting  phloridzin  into  the  mother,  and  thus  reducing  the  glycogen 
store  of  the  fcetus  (Lochead  and  Cramer).  Probably,  then,  the  fcttal 
glycogen  assists  the  growth  of  the  embryo,  which  is  known  to  Ix 
accompanied  by  an  intense  carbo-hydrate  metabolism,  by  furnishing 
a  store  of  easily  oxidized  iv..iteiial  iox  the  nutrition  of  the  developing 

69 


lOQo  REPRODUCTION 

tissues.  When  the  muscles  have  been  formed,  their  glycogen  is 
still  consumed  in  growth,  and  their  functional  powers  lie  dormant, 
but  for  the  infrequent  and  feeble  movements,  generally  regarded  as 
reflex,  but  possibly  to  some  extent  originated  in  the  cerebral  cortex, 
which  give  the  mother  the  sensation  of  '  quickening.'  It  is  only 
late  in  development  that  the  embryonic  liver  takes  on  its  glycogenic 
function.  In  the  earlier  stages  it  is  entirely  free  from  glj'cogen.  It 
is  an  interesting  illustration  of  that  exact  adaptation  of  means  to 
ends  which  so  constantly  impresses  the  investigator  of  the  animal 
mechanism  that  the  ferment  which  converts  gl3'cogen  into  dextrose 
(glycogenase)  is  also  either  entirely  absent  from  the  liver  early  in 
gestation,  or  present  only  in  traces ;  and  that  as  the  glycogen-forming 
and  glycogen-storing  functions  of  the  organ  increase  in  importance,  it 
becomes  richer  in  glycogenolytic  ferment.  It  cannot  be  doubted  that 
the  glycogen  found  in  the  placenta  is  also  deposited  there  in  the 
interest  of  the  rapidly  growing  foetal  tissues,  perhaps  as  a  kind  of 
current  account  on  which  they  can  operate  at  any  moment  of 
emergency,  when  the  more  distant  maternal  reserves  cannot  be 
drawn  upon  in  time.  The  glycogen  is  formed  in  the  placenta,  prob- 
ably from  the  dextrose  of  the  maternal  blood.  By  means  of  a 
glycogen-splitting  ferment,  which  can  be  extracted  by  glycerin  from 
the  placenta,  the  glycogen  appears  to  be  reconverted  into  dextrose 
for  absorption  by  the  foetus.  In  the  earlier  period  of  gestation  the 
placenta  seems  to  perform  vicariously  the  glycogenic  function  of  the 
liver,  and  as  the  glycogen  content  of  the  liver  increases  in  the  later 
stages  of  intra-uterine  life,  that  of  the  placenta  diminishes  pro- 
portionally. 

The  excretory  glands  of  the  embryo,  except  the  liver,  scarcely 
awaken  to  activity  during  foetal  life.  Urine  may  indeed  be  some- 
times found  in  the  bladder  at  birth,  but  it  is  often  absent.  It  is  a 
dilute  urine,  with  a  molecular  concentration  only  about  half  as  great 
as  that  of  the  blood,  and  although  a  portion  of  the  amniotic  fluid, 
which  contains  traces  of  urea  and  salts,  in  addition  to  small  quantities 
of  albumin,  may  be  secreted  by  the  renal  tubules,  and  find  its  way 
through  the  still  open  urachus  into  the  amniotic  sac,  this  contribution 
cannot  imply  more  than  a  slight  degree  of  glandular  action.  Under 
certain  experimental  conditions,  however,  it  can  be  largely  increased. 
Thus,  extirpation  of  the  kidneys  in  a  pregnant  animal  causes  an 
increase  in  the  amount  of  amniotic  fluid  (hydramnios)  through  the 
stimulation  of  the  foetal  kidneys  to  increased  activity  by  the  passage 
of  the  unexcreted  urinary  constituents  of  the  mother's  blood  into 
that  of  the  foetus.  After  the  injection  of  phloridzin  into  the  foetus 
sugar  has  been  found  in  abundance  in  the  amniotic  fluid,  although 
the  injection  of  that  drug  into  the  mother  caused  no  such  effect.  On 
the  other  hand,  after  injection  of  sodium  sulphindigotate  into  the 
circulation  of  the  foetus  in  the  sheep,  the  foetal  kidneys  contained 


NUTIilTIOK  OF  THE  EMUKYU  1091 

particles  of  the  pigment,  while  the  amniotic  fluid  remained  un- 
coloured.  Long  before  full  term  the  sebaceous  glands  have 
begun  their  work  by  the  secretion  of  the  vernix  caseosii,  an 
oily  material  which  covers  the  skin  and  serves  to  protect  it 
from  the  continual  irritation  of  thf  fluid  in  which  the  embryo 
floats. 

The  nervous  system  is  even  less  active  than  the  glandular  tissues, 
and  not  more  active  than  the  muscles.  There  is  evidently  no  scope 
for  the  exercise  of  the  special  senses.  Psychical  activity  of  every 
kind  must  be  at  its  lowest  ebb.  Consciousness,  if  it  exists  at  all, 
must  be  dull  and  muffled.  And  if  motor  impulses  are  discharged 
from  the  cortex,  the  psychical  accompaniments  of  such  discharge  are 
doubtless  widely  different  from  those  which  we  associate  Nvith 
voluntary  effort. 

It  is  a  remarkable  fact  that  this  functional  calm,  broken  only  by 
the  beat  of  the  heart,  is  accompanied  by  a  relatively  intense 
metabolism  of  the  same  order  of  magnitude  as  that  of  the  adult. 
In  the  hen's  egg  at  all  stages  of  development  the  consumption  of 
oxygen  and  production  of  heat  (per  kilogramme  and  hour)  are  the 
same  as  in  the  adult  hen.  The  oxygen  consumption  and  carbon 
dioxide  production  of  pregnant  guinea-pigs  were  determined  before 
and  during  compression  of  the  umbilical  cord  of  a  foetus,  and  a  dis- 
tinct diminution  was  observed  when  the  respiratory  exchange  of  the 
foetus  was  eliminated.  From  the  results  of  a  number  of  observations 
it  was  calculated  that  the  carbon  dioxide  produced  by  the  mother 
was  462  c.c,  and  by  the  foetus  509  c.c.  per  kilogramme  of  body- 
weight  per  hour  (Bohr  and  Hasselbach).  A  similar  comparison 
between  women  before  and  during  pregnancy  never  showed  any 
diminution  in  therespiratory  exchange  reckoned  on  the  unit  of  body- 
weight  in  the  pregnant  condition.  In  one  case,  indeed,  and  that 
the  most  exactly  observed,  there  was  an  increase  in  pregnancy. 
Now,  in  the  pregnant  woman  a  considerable  part  of  the  increase  of 
body- weight  is  due  to  the  amniotic  fluid,  in  which,  of  course,  meta- 
bolism does  not  go  on.  It  is  evident,  then,  that  in  the  human  foetus 
also  the  intensity  of  metabolism  is  at  any  rate  not  of  a  lesser  order  of 
magnitude  than  in  the  mother,  in  spite  of  the  much  smaller  amount 
of  muscular  contraction  taking  place.  The  heat  production  of  mother 
and  child  together  has  been  directly  estimated  in  several  cases  in  a 
respiration  calorimeter  provided  with  a  bed  just  before  parturition 
and  just  after  it.  After  parturition  the  heat  production  of  the 
mother  was  also  separately  determined.  From  the  difference  it  was 
concluded  that  the  heat  production  of  the  child  per  kilogramme 
of  body-weight  per  hour  is  approximately  two  and  a  half  times 
that  of  the  mother  under  the  same  conditions.  (Carpenter  and 
Murlin.) 

The  foetal  heart  beats  at  the  rate  of  about  140  times  a  minute  at 


I092  REPRODUCTION 

full  term.*  The  blood-pressure  in  the  umbilical  artery  of  the 
mature  embryo  (sheep)  varies  from  60  to  80  mm.  of  mercury; 
but  at  the  beginning  of  the  aorta  it  will  be  more.  The  pressure  in 
the  pulmonary  trunk  must  be  about  equal  to  that  in  the  aorta,  since 
the  comparatively  short  and  easy  circuit  through  the  limgs  does 
not  as  yet  exist ;  and  in  accordance  with  this  equality  of  pressure 
(of  work  to  be  done)  is  the  equahty  of  thickness  (of  working  power) 
in  the  walls  of  the  two  sides  of  the  heart. 

Suppose,  now,  that  the  embryo  contains  60  grammes  of  blood  for 
every  kilo  of  body-weight,  and  that  the  whole  of  the  blood  passes 
through  the  circulation  in  twenty  seconds.  Then  in  twenty-four 
hours  2592  kilos  of  blood  will  be  forced  through  the  heart  for  every 
kilo  of  body-weight  against  a  pressure  of,  say,  80  mm.  of  mercury, 
or  I  metre  of  blood.  This  is  equivalent,  in  round  numbers,  to  260 
kilogramme-metres  of  work,  or  06  calories.  Now,  taking  the  total 
heat-production  of  the  heart  at  three  times  the  equivalent  of  its 
mechanical  work,  we  get  18  calories  per  kilo  of  body- weight  in 
twenty- four  hours  (see  p.  663),  or  about  t/^  of  the  heat-production 
of  a  resting  adult. 

Such  movements  of  the  skeletal  muscles  as  occur  cannot  account 
for  any  large  proportion  of  the  total  metabolism,  since  they  are 
executed  in  a  medium  (the  amniotic  fluid)  of  nearly  the  same  specific 
gravity  as  that  of  the  body,  and  therefore  require  the  expenditure  of 
a  very  limited  amount  of  energy.  The  ordinary  functional  activity 
of  the  embryo,  then,  is  quite  incapable  of  accounting  for  the  intensity 
of  the  foetal  metabolic  processes.  Still  less  can  it  be  due  to  an  active 
combustion  in  the  tissues  to  compensate  for  a  rapid  loss  of  heat, 
for  the  foetus  lies  sheltered  in  the  uterus  as  in  a  thermostat  at  its 
own  temperature,  and  can  lose  practically  no  heat  unless  its  tempera- 
ture be  kept  a  little  above  that  of  the  maternal  blood.  The  only 
remaining  explanation  of  the  magnitude  of  the  foetal  metabolism 
is  that  the  growth  processes  are  associated  with  a  large  amount  of 
oxidation  (and  cleavage). 

Notwithstanding  the  intensity  of  metabohsm  in  the  embryo,  not 
only  is  even  the  purest  blood,  as  has  already  been  stated,  far  from 
saturated  with  oxygen,  but  the  relative  proportion  of  haemoglobin, 
the  oxygen-carrier,  is  less  than  in  the  adult ;  and  although  constantly 
increasing  in  amount  from  the  moment  of  its  first  appearance,  it  is 
still  somewhat  deficient,  even  at  full  term,  but  leaps  sharply  up  at 

*  It  has  not  been  finally  determined  whether  the  rate  of  the  heart  varies 
with  the  size  or,  what  probably  comes  to  the  same  thing,  with  the  sex  of  the 
foetus.  As  we  have  seen,  the  variation  of  the  rate  in  the  adult  with  the  size 
of  the  body  is  associated  with  a  corresponding  variation  in  the  metabolism 
and  heat-loss,  which  are  proportionally  greater  in  a  small  than  in  a  large 
animal.  If  this  is  a  causal  connection  we  should  not  expect  that  in  the 
embryo  in  utero .  wliere  the  conditions  as  regards  heat-loss  are  entirely  different, 
such  a  relation  should  exist,  at  any  rate  within  the  same  species. 


PARTURITION  1093 

birth.  At  an  early  period  of  development  the  embryo  also  contains 
much  more  water  than  the  adult;  the  specific  gravity  of  its  tissues 
increases  as  development  goes  on. 

The  remarkable  vitahty  of  the  frietus,  and  its  resistance  to 
asphyxia,  are  related  not  to  the  feebleness  of  its  metabohsm,  but  to 
the  comparatively  slight  excitability  and  high  endurance  of  nervous 
centres  like  the  respiratory,  vaso-motor,  and  cardio-inhibitory. 
Even  when  totally  deprived  of  oxygen,  as  by  pressure  on  the  um- 
bilical cord  during  delivery,  the  child  floes  not  perish  in  the  two  or 
three  minutes  which  decide  the  fate  of  the  asphyxiated  adult ;  nor  arc 
the  convulsions,  rise  of  blood-pressure,  and  slowing  of  the  heart-beat 
associated  with  asphyxia  in  the  latter,  so  readily  induced,  nor 
premature  and  fatal  efforts  at  respiration  easily  excited  in  uiero. 
But  although  in  such  a  case  the  embryo  behaves  as  a  separate 
organism,  governed  by  its  own  laws,  there  are  circumstances  in 
which  it  becomes  merely  a  part  of  the  mother  and  participates  in  her 
fate.  Thus,  the  stream  of  oxygen  which  normally  passes  from  the 
maternal  to  the  foetal  blood  is  turned  back  if  asphyxia  threatens 
the  mother;  the  blood  of  the  umbilical  arteries,  instead  of  being 
purified  in  the  placenta,  loses  the  little  oxygen  it  holds  to  the 
blood  of  the  uterine  sinuses,  and  the  tissues  of  the  embryo  are 
impoverished  to  support  the  metabolism  of  the  maternal  organs. 
In  the  same  way,  the  phenomena  of  starvation  have  taught  us 
that  the  nutrition  of  the  organism  is  not  subject  to  the  rules  of 
red  tape.  In  normal  circumstances  the  flow  of  nutriment  follows 
definite  lines:  the  blood  feeds  the  tissues  through  its  intermediary, 
the  lymph,  and  recoups  itself  from  the  contents  of  the  alimentary 
canal.  But  when  the  normal  sources  of  nutrient  material  fail,  the 
body  falls  back  upon  its  stores.  The  organs  immediately  ni'cessary 
to  life  are  kept,  as  far  as  possible,  on  full  diet ;  organs  of  secondary 
importance  have  to  be  content  with  half-rations;  organs  less  im- 
portant still  are  drawn  upon  for  supplies. 

Parturition, — The  period  of  gestation  is  abruptly  closed  about 
28«- days  after  the  last  menstruation,  usually  in  what  would  have 
been  the  tenth  intermenstrual  period  had  menstruation  bien  occur- 
ring. There  is  necessarily  a  considerable  variation  in  the  time  when 
reckoned  in  this  way,  since  the  cessation  of  the  menses  merely  an- 
nounces that  conception  has  occurred  some  time  after  the  last 
period.  It  may  even  be  disputed  whether  the  fertilizeii  ovum 
corresponds  to  the  last  menstruation  or  to  the  first  absent 
period.  Parturition,  or  the  expulsion  of  the  foetus,  is  accom- 
plished by  periodical  contractions,  the  '  pains  '  of  labour,  at  first 
confined  to  the  uterus.  Soon  the  os  uteri  begins  to  soften  antl 
dilate,  the  walls  of  the  vagina  become  congested,  and  its  secretions 
are  augmented.  The  uterine  contractions  increase  in  frequency 
and  force,  and  are  now  accompanied  by  reflex  contractions  of  the 


I094  REPRODUCTION 

abdominal  muscles,  and,  if  the  woman  is  not  anaesthetized,  also  by 
voluntary  contractions  of  these  and  of  other  muscles,  which  can 
increase  the  intra-abdominal  pressure.  The  uterine  contractions 
can  be  initiated  and  modified  by  impulses  coming  from  the  central 
nervous  system  by  way  of  the  extrinsic  nerves  of  the  organ.  It  is 
known,  e.g.,  that  the  gravid  uterus  can  be  excited  to  contraction  by 
the  stimulation  of  various  sensory  nerves.  Powerful  mental  impres- 
sions, such  as  fright,  may  bring  on  premature  labour.  Conversely, 
sudden  cessation  of  labour  pains  during  parturition  is  not  uncom- 
monly observed  to  be  produced  by  emotional  disturbances — ^for 
instance,  the  entrance  of  a  stranger  into  the  room.  Yet  the  con- 
tractions of  the  uterus  are  not  essentially  dependent  upon  extrinsic 
impulses.  For  not  only  do  rhythmical  contractions  occur,  but  the 
whole  process  of  parturition  has  been  seen  to  take  place  in  a  uterus 
whose  nerves  have  all  been  cut.  Even  the  excised  uterus  may  be 
kept  alive  for  as  long  as  forty-eight  hours,  and  may  go  on  executing 
periodical  contractions  when  its  bloodvessels  are  perfused  with  such 
an  artificial  fluid  as  Locke's  solution,  or,  indeed,  when  it  is  simply 
immersed  in  the  oxygenated  solution  (Kurdinowski)  (Practical 
Exercises,  p.  iioi). 

It  is  a  question  of  great  interest  how  the  uterine  contractions  are 
started  so  abruptly  at  full  term  after  so  long  a  period  of  quiescence. 
It  can  hardly  be  that  the  increasing  mechanical  distension  of  the 
uterus,  tolerated  for  so  many  months,  should  suddenly,  in  an  hour, 
become  intolerable.  For  if  the  foetus  dies  before  full  term  it  is 
expelled  without  reference  to  the  bulk  which  the  uterus  has  reached. 
It  is  more  likely  that  some  chemical  change  associated  with  the 
completion  of  intra- uterine  development,  a  change  which  leads, 
perhaps,  to  the  production  of  some  specific  substance  in  the  placenta 
or  the  foetus,  is  the  determining  event.  The  placenta  is  a  structure 
whose  function  is  strictly  limited  to  the  term  of  intra-uterine  develop- 
ment. The  foetus  is  to  live  on,  and  so  is  the  mother.  May  it  not 
be  that  the  placenta  or  essential  elements  in  it  are  timed  to  die,  or 
to  begin  to  die,  at  full  term,  and  that  in  their  death  or  degeneration 
the  substance  or  substances  are  produced  which  start,  and  later 
sustain,  the  uterine  contractions  ?  And  may  not  the  contractions  of 
the  uterus,  by  exciting  its  afferent  nerves,  or  through  the  pressure 
of  the  foetus  the  afferent  nerves  of  the  vagina,  in  turn  evoke  the 
associated  reflex  contractions  of  the  abdominal  walls  ?  These  are 
questions  which  have  been  asked,  but  not  as  yet  satisfactorily 
answered.  It  has  also  been  suggested  that  a  hormone  formed  in  the 
mammary  gland  at  full  term  stimulates  the  uterus  and  thus  brings 
on  labour. 

At  birth,  great  changes  take  place  in  the  foetal  circulation,  and  these 
are  intimately  connected  with  the  commencement  of  the  respiratory 
activity  of  the  lungs.     The  causes  of  the  first  respiration  are:  (i)  The 


MILK  1095 

increasing  venosity  of  the  blood  circulating  in  tlic  bulb,  wliich  stimu- 
lates the  respiratory  centre  wlu-n  the  umbilical  cord  has  Ix-cn  cut  or 
tied  and  the  placental  circulation  thus  interfered  witli ;  (-j)  tlie  stimula- 
tion of  the  skni  by  the  air,  which,  as  we  have  seen,  acts  rellcxly  upon  the 
respiratory  centre,  'liiat  both  of  these  factors  may  b<-  involved  is 
shown  by  the  fact  that  eitlur  compression  of  the  umbilical  cord  alone, 
or  exposure  of  the  foetus  by  opening  tiie  uterus  of  an  animal  without 
interference  with  the  circulation,  has  been  observed  to  be  followed 
by  attempts  at  breathing.  (Jncc  distended,  the  lungs  never  again 
completely  collapse — ^not  even  after  death,  nor  when  the  chest  is 
opened.  The  aspiration  caused  by  the  elevation  of  the  chest-walls  in 
inspiration  (for  the  respiration  of  the  newborn  child  is  mainly  costal) 
sucks  blood  into  the  thorax,  and  expands  the  vessels  of  the  lungs  for 
its  reception  ;  and  in  the  measure  in  which  the  blood  passing  through  the 
pulmonary  trunk  finds  an  easy  way  through  the  lungs,  tlie  Quantity 
wliich  takes  the  route  of  the  ductus  arteriosus  diminishes.  The  pul- 
monary veins,  and  consequently  the  left  auricle,  are  better  tilled;  and 
the  increasing  pressure  on  this  side  of  tlie  septum  tends  to  oppose  the 
passage  of  tlic  blood  through  the  foramen  ovale,  to  approximate  its 
valve,  and  to  close  its  orifice. 

By  the  second  or  third  day  the  ductus  arteriosus  has  usually  become 
obliterated.  Tiie  umbilical  arteries  and  veins  and  the  ductus  venosus 
become  impervious  soon  after  the  interruptioa  of  the  j)laccntal  circula- 
tion. The  vein  and  venous  duct  remain  in  the  adult  as  the  round 
ligament  of  the  liver,  the  arteries  as  the  lateral  ligaments  of  the  bladder. 

Although  from  birth  onwards  the  young  mammal  obtains  its 
oxygen  and  gets  rid  of  its  carbon  dioxide  through  its  own  pulmonary 
surface  instead  of  through  the  placenta,  it  still  lives,  as  regards  its 
food  proper,  on  the  tissues  of  the  mother,  and  that  in  as  literal  a 
sense  as  when  it  drew  its  supplies  directly  from  the  maternal  blood. 

Milk. — ^The  milk  secreted  during  the  first  few  days  of  each  lacta- 
tion, the  colostrum,  as  it  is  called,  indeed  may  represent  in  part  the 
fragments  of  cells  lining  the  alveoli  of  the  mammary  glands,  which 
have  undergone  a  fatty  change  and  been  bodily  broken  down.  The 
colostrum  corpuscles  are  leucocytes  filled  with  fat  globules  taken  up 
from  the  contents  of  the  alveoli.  The  chief  chemical  difference 
between  colostrum  and  ordinary  milk  is  the  greater  richness  of  the 
former  in  protein.  It  has  been  supposetl  that  it  is  of  special  impor- 
tance for  the  nutrition  of  the  suckling,  perhaps  in  virtue  of  the 
enzymes  contained  in  it,  and  it  is  said  that  young  animals  bear 
artificial  feeding  much  better  if  they  have  been  allowed  to  suckle  the 
mother  for  the  colostrum. 

In  addition  to  the  fat,  which  when  milk  is  allowed  to  stand  rises  to 
the  top  as  cream,  milk  contains  a  consiilerablc  quantity  of  casoinogcn, 
to  whose  coagulation,  under  the  influence  of  the  lactic  acid  prcnluccd 
from  the  lactose,  or  milk-sugar,  by  certain  bacteria,  spontaneous 
curdling  is  due.  Another  protein,  lact-albumin  (Halliburton),  a  large 
amount  of  water,  and  some  inorganic  salts,  are  the  most  imi>cirtant  of  its 
remaining  constituents.  The  molecular  concentration  (p.  4-20)  of  milk. 
as  measured  by  its  frec/ing-point,  is  almost  exactly  the  same  as  that  of 
blood-serum.     Its   electrical    conductivity    varies  extremely,   since   it 


1096 


REPRODUCTION 


depends  on  the  quantity  of  fat  present,  the  fat  globules,  like  the  blood- 
corpuscles,  being  practically  non-conductors. 

The  inorganic  composition  of  milk  is  particularly  interesting  when 
compared  with  that  of  the  blood  on  the  one  hand  and  that  of  the 
suckling  on  the  other.  Thus,  100  grammes  of  ash  from  each  source 
gave  the  following  values  for  the  rabbit  (Abderhalden) : 


Rabbits  (14  Days 
Old). 

Rabbit's  Milk. 

Rabbit's  Blood. 

Rabbit's  Blood- 
serum. 

K20 

IO'84 

IO'06 

23-75 

3-19 

NagO 

5-96 

7.92 

31-38 

54-72 

CaO 

35-02 

35-65 

o-8i 

1-42 

MgO 

2-19 

2-20 

0-64 

0-56 

FeaOg 

0*23 

o-o8 

6-93 

o-oo 

P2O6 

41-94 

39.86 

ii-ii 

2-98 

CI    .. 

4*94 

5-42 

32-66 

47-83 

The  richness  of  the  milk  (and  of  the  suckling)  in  calcium,  phos- 
phoru-s,  and  magnesium,  as  compared  with  the  serum,  is  to  be  especially 
remarked.  This  is,  of  course,  essential  for  the  development  of  the 
bones.  Whereas  sodium  predominates  greatly  over  potassium  in  the 
serum,  the  opposite  is  the  case  in  the  milk  (and  the  suckling).  This  is 
connected  with  the  development  of  the  tissue  cells,  which  are  richer  in 
potassium  than  in  sodium.  The  high  chlorine  content  of  the  serum  is 
in  sharp  contrast  wAth  the  relative  poverty  of  the  milk  in  that  element, 
which  preponderates  in  the  tissue  liquids  and  is  relatively  scanty  in  the 
cells. 

In  addition  to  substances  susceptible  of  chemical  analysis,  milk 
contains  enzymes  like  those  present  in  blood-serum,  including 
oxydases  and  various  hydrolytic  ferments  (proteolytic,  diastatic, 
and  perhaps  lipolytic).  It  is  now  universally  acknowledged  that 
mother's  milk  is  superior  for  the  feeding  of  the  infant  to  any 
artificial  substitute,  and  one  factor  in  this  superiority  may  be  the 
presence  of  ferments  specifically  adapted  for  the  digestion  of  the 
human  suckling.  More  important  is  the  practical  sterility  of  the 
human  milk  and  the  necessarily  finer  adaptation  of  its  quantitative 
and  qualitative  composition,  particularly  the  closer  relationship  of 
its  proteins  with  those  of  the  child.  In  addition,  there  is  some 
evidence  that  the  maternal  milk  contains  immune  bodies  (anti- 
bodies) which  may  increase  the  resistance  of  the  suckling  to 
infections. 

However  this  may  be,  there  is  no  question  that  much  of  the  high 
infant  mortality  associated  with  the  industrial  conditions  of  our 
great  cities  could  be  prevented  if  breast-feeding  were  carried  out  by 
every  mother  physically  capable  of  it. 

As  to  the  manner  in  which  milk  is  secreted,  there  is  no  doubt 
that  its  chief  constituents  are  formed  in  the  gland-cells.  Caseinogen 
and  lactose  do  not  exist  in  the  blood  or  lymph.     The  former  is 


CULTIVATION  OF  TISSUES  1097 

probably  produced  by  an  alteration  in  one  or  other  of  the  serum 
proteins,  the  latter  by  a  change  in  the  dextrose  of  the  blood.  The 
fat  of  the  milk  may  come  partly  from  the  fat  of  the  blood,  but  it 
may  also  be  formed  in  the  gland-cells  from  proteins  and  carbo- 
hydrates. The  precise  manner  in  which  the  fat  globules  are  extruded 
from  the  cells  into  the  lumen  of  the  alveoli  is  not  clear,  but  there  is 
no  good  ground  for  believing  that  the  cells  or  their  free  ends  break 
up  bodily  in  the  process. 

Little  is  known  as  to  the  influence  of  the  nervous  system  on  the 
secretion  of  milk,  and  no  definite  secretory  fibres  have  as  yet  been 
clearly  demonstrated,  although  the  fact  that  marked  changes  may 
be  produced  in  the  milk  of  nursing  women  as  the  result  of  emotional 
disturbances  indicates  that  such  nerves  do  exist. 

Pregnancy  is  accompanied  with  vascular  dilatation  and  h\'per- 
trophy  of  the  mammary  glands,  but  the  mechanism  by  which  thc^e 
changes  are  produced  is  unknown.  It  is  probable  that  they  depend 
upon  some  internal  secretion  of  the  ovary  or  some  other  of  the 
organs  of  reproduction.  Pregnancy  is  not  an  absolutely  indispens- 
able condition,  and  therefore  it  would  seem  that  the  exciting 
substance,  if  any  specific  substance  exists,  is  not  a  product  of  the 
foetus  or  of  the  placenta.  Precisely  similar  phenomena  are  occasion- 
ally seen  in  animals  which  have  not  been  impregnated  and  even  in 
men.  Humboldt  relates  the  case  of  an  Indian  father,  who  so  well 
understood  the  responsibilities  of  paternity,  and  was  so  capable 
of  fulfilling  them,  that  he  suckled  his  child  for  five  months  on  the 
death  of  the  mother.  Virgin  bitches  are  frequently  known  to 
produce  milk,  occasionally  even  in  quantity  sufficient  to  rear  pups, 
the  flow  occurring  about  the  time  when  they  would  have  whelped 
had  they  conceived  during  the  previous  oestrus  (period  of  heat). 
Bitches  which  after  copulation  have  '  missed  '  having  pups  have 
been  known  to  produce  so  much  milk,  beginning  at  the  time  they 
were  due  to  whelp,  that  they  were  able  to  rear  litters  of  puppies 
belonging  to  other  bitches.  Mules,  which  are  themselves  sterile, 
may  have  enough  milk  to  suckle  a  foal.  The  nipples  of  certain 
monkeys  become  swollen  and  congested  at  each  menstruation 
(Heape),  and  in  women  some  development  of  the  mammary  glands 
is  often  associated  with  the  menstrual  period.  The  stimulus  to  the 
development  of  the  gland  in  these  cases  appears  to  be  some  change 
correlated  with  oestrus,  and  cannot  be  a  change  correlated  with 
pregnancy. 

Cultivation  of  Tissues  outside  of  the  Body. — Closely  related  to  the 
marvellous  power  of  growth  of  the  fertilized  ovum  in  the  favourable 
nidus  of  the  pregnant  uterus,  although,  of  course,  incomparably 
inferior,  is  the  power  of  growth  and  reproduction  of  isolated  tissue 
cells  in  a  suitable  medium  outside  of  the  body.  An  instance  of 
this  has  already  been  described  in  the  case  of  nerve-cells  (p.  829). 


1098  REPRODUCTION 

Many  other  tissues  have  been  successfully  cultivated  in  sterile 
coagulated  lymph  or  blood-plasma.  Connective-tissue  cells  grow 
very  easily,  and  can  apparently  be  preserved  indefinitely  in  the 
living  state.  A  strain  of  these  cells,  originally  obtained  from  a 
fragment  of  the  heart  of  an  embryo  chick  which  had  been  pulsating 
in  vitro  for  104  days,  has  been  seen  to  proliferate  rapidly  outside  of 
the  organism  for  more  than  sixteen  months,  and  after  more  than 
190  passages  into  fresh  media.  At  the  end  of  this  time  the  rate  of 
proliferation  of  the  connective-tissue  cells  was  even  greater  than 
that  of  fresh  connective  tissue  taken  from  an  embrj'o  eight  days  old. 
Extracts  of  tissues  and  tissue  juices  under  certain  conditions  acceler- 
ate the  growth  of  connective  tissue  from  three  to  forty  times,  the 
growth  being  measured  by  the  increase  in  area  of  the  minute  pieces 
of  tissue.  This  activating  power  is  especially  marked  in  extracts 
of  embryos,  of  adult  spleen,  and  of  certain  sarcomas.  This  is  of 
great  interest  as  the  great  characteristic  of  malignant  tumours  is 
their  indefinite  power  of  growth.  The  activating  substance  is 
unable  to  pass  through  a  Chamberland  filter  (Carrel).  Cultures  of 
adult  tissue  have  a  smaller  power  of  persistent  growth.  In  the 
majority  of  cases  growth  in  plasma  without  the  addition  of  a 
stimulating  tissue  extract  ceases  after  three  or  four  generations 
(Walton).  » 

The  time  of  survival  of  tissues  at  low  temperatures  under  con- 
ditions which  do  not  encourage  growth  is  also  a  matter  of  consider- 
able interest,  both  from  the  physiological  and  the  practical  point  of 
view,  since  living  sterile  tissue  is  required  for  a  number  of  surgical 
operations — for  example,  skin  for  grafting.  Skin  has  been  suc- 
cessfully grafted  after  being  kept  two  to  seven  weeks  in  cold  storage, 
but  after  a  longer  period  there  were  many  failures.  Embryonic 
chick  and  rat  tissues  live  longest  at  about  6°  C,  but  not  more  than 
twenty  days  under  the  most  favourable  conditions,  according  to 
Lambert. 

Transplantation  of  Tissues. — ^Besides  the  growth  and  regeneration 
of  tissues  or  organs,  the  simple  displacement  of  them  from  their 
normal  situation  and  their  implantation  in  a  new  environment  have 
been  studied.  Normally,  a  migration  of  tissue  elements  is  only 
witnessed  in  the  adult  in  the  case  of  cells  moving  with  the  circulating 
liquids,  or  endowed  with  the  power  of  amoeboid  movement.  Under 
pathological  conditions  fragments  of  tissue,  such  as  tumour  cells, 
may  be  carried  by  the  blood  or  lymph  to  distant  parts,  and,  settling 
there,  may  undergo  development  (forming  metastases).  In  the 
embryo  the  slow  migration  of  tissue  elements  is  a  process  which 
is  responsible  for  some  of  the  anatomical  pecuharities  of  the  adult. 
The  migration  of  the  ovum  from  the  ovary  is  the  starting-point  of 
the  process  of  reproduction.  The  artificial  displacement  of  tissues 
within  the  body  of  one  and  the  same  animal  (auto-  or  homo-trans- 


TRANSPLANTATION  OF  1  ISSUES 


1099 


plantation,  or  graft),  or  from  one  animal  to  another  of  the  same 
species  (iso-transplantation,  or  graft)  has  been  successfully  accom- 
plished in  many  cases.  ]3ut  hetero-transplantation,  or  grafting 
between  animals  of  different  species,  is  in  general  not  permanently 
successful,  the  graft  undergoing  cytolysis  (p.  31)  in  the  alien 
environment. 

Transplantation,  or  engrafting,  may  be  done  either  with  or  without 
anastomosis  of  bloodvessels.  In  the  second  method  a  portion  of 
tissue,  usually  small,  or  a  small  organ,  is  simply  inserted  in  its  new 
situation  without  provision  for  the  immediate  establishment  of  a 
circulation  in  it.  Strips  of  cuticle  may  easily  be  grafted  in  this  way 
to  restore  deficiencies  in  the  skin  after  burns  or  extensive  opera- 


Fig.  463. — Method  of  Transplantation  (of  both  Kidneys)  in  Mass  (after  Guthrie). 
Segments  of  the  inferior  vena  cava  and  abdominal  aorta  are  removed  with  the 
kidneys  and  renal  vessels,  and  interposed  in  the  course  of  the  vena  cava  and  aorta 
of  another  animal,  according  to  the  method  of  Carrel  and  Guthrie. 

tions.  The  ovary  can  also  be  grafted  by  simple  implantation  with 
success.  Guthrie  has  thus  shown  that  hens  whose  ovaries  have  been 
interchanged  are  capable  of  la\ing  eggs.  When  the  hens  were 
impregnated  and  the  eggs  hatched  out  the  colour  characters  of  the 
resulting  offspring  seemed  to  have  been  influenced,  not  only  by  the 
hen  to  which  the  ovary  originally  belonged,  but  also  by  the  hen  to 
which  it  had  been  transferred.  Grafts  of  the  thyroid  and  para- 
thyroid have  also  been  shown  to  '  take.' 

In  transplantation  with  anastomosis  of  bloodvessels  the  main 
vessels  of  the  engrafted  organ  are  sutured  to  suitable  arteries  and 
veins  in  the  '  host,'  so  that  the  circulation  is  at  once  effective.  Con- 
sequently there  is  practically  no  limit  to  the  size  of  the  grafts.     The 


IIOO 


REPRODUCTION 


kidney,  spleen,  and  even  a  limb,  have  been  successfully  transplanted 
in  this  way  from  one  dog  to  another.  Segments  of  arteries  preserved 
in  cold  storage  for  a  few  days  or  even  weeks,  and  even  portions  of 
arteries  fixed  by  formaldehyde,  have  been  transplanted  so  as  to  take 
the  place  of  segments  removed  from  arteries  of  living  animals,  and 


Fig.  464. — Suturing  Bloodvessels:  Preliminary  Fixation  of  Ends  of  Divided  Vessels 
(after  Guthrie).  Three  fixing  ligatures  are  placed  at  equidistant  points  on  the 
circumference  of  the  cut  ends,  each  ligature  being  passed  through  corresponding 
points  of  the  two  vessels.  The  ends  of  the  vessels  are  approximated  by  drawing 
on  the  ligatures,  which  are  then  tied,  and  the  margins  of  the  vessels  sewed  together 
by  continuous  stitches  in  the  intervals  between  the  fixing  ligatures,  as  in  Fig.  465. 
(Carrel's  method.) 

have  continued  to  function  perfectly  for  long  periods.  Portions  of 
veins  have  also  been  used  to  fill  up  gaps  in  arteries.  Even  hetero- 
plastic vascular  grafts  have  been  found  to  succeed,  portions  of  dog's 
arteries,  e.g.,  grafted  into  a  cat,  and  portions  of  rabbit's,  cat's,  or 


Fig.  465. — Suturing  Bloodvessels:  Method  of  approximating  Edges  and  putting  in 
Continuous  Suture  (after  Guthrie).  The  needles  are  very  fine  cambric  sewing- 
needles,  and  the  threads  single  strands  of  Chinese  twist  silk  or  human  hair. 
Needles  and  threads  are  sterilized  in  paraffin-oil.     (Method  of  Carrel  and  Guthrie.) 

human  arteries  grafted  into  a  dog.  Doubtless  the  favourable  result 
is  largely  due  to  the  fact  that  the  function  of  the  large  arteries  is 
mainly  a  passive,  mechanical  one,  which  can  be  discharged  even  by 
a  dead  tube  of  the  requisite  strength,  and  with  the  smooth  interior 
presented  by  a  dead  endothelial  lining  (Carrel,  Guthrie). 


PARABIOSIS 


Parabiosis. — ^Xot  only  may  an  organ  or  a  portion  of  tissue  from 
one  individual  be  engrafted  on  another,  but  two  individuals  may  be 
so  united  that  a  greater  or  smaller  degree  of  physiological  in- 
timacy is  produced  between  them.  Occasionally,  as  in  the  famous 
Siamese  twins,  an  anomaly  of  development  results  in  such  close 
anatomical  union  of  the  circulatory  and  other  systems  that  in 
certain  respects  the  two  individuals  constitute  almost  a  single 
organism,  and  cannot  be  separated  by  surgical  interference.  A 
less  intimate  union  can  be  established  experimentally  by  opening 
the  peritoneal  cavities  of  the  two  animals,  and  suturing  the  skin 
and  connective  tissue  together  so  as  to  permit  of  permanent 
communication.  Pairs  of  animals  living  in  this  condition  (so- 
called  parabiosis)  have  been  utilized  for  the  study  of  certain 
questions  in  immunity.  White  rats  have  been  kept  alive  in  para- 
biosis for  as  long  as  thirty-four  days  in  order  to  test  the  question 
whether  destructive  antibodies  for  cancer  are  present  in  the  circula- 
tion (Rous),  since  it  has  been  shown  that  circulating  antibodies  easily 
pass  from  one  to  the  other  of  such  a  pair  of  animals  (Ehriich.) 
One  of  each  pair  of  rats  had  a  growing  tumour  produced  by 
transplantation,  while  the 
other  had  been  proved  resis- 
tant to  the  same  type  of 
tumour.  No  evidence  of  the 
passage  of  an  antibody  was 
found  in  this  case. 


PRACTICAL  EXERCISE. 


Contractions     of     Isolated 
Uterine  Rings. — Kill   a   female 
adult  rabbit  by  striking  it  at 
the  back  of  the  neck.     A  rabbit 
which  is  not  pregnant,  or  only 
at  the  beginning  of  pregnancy, 
should  be  selected.     Open  the 
abdomen,  and  carefully  remove 
the  uterus.     While  separating 
the     organ     from     the     broad    Fig.  466— Contractions  of  Rabbits    Uterus 
ligament   and   vagina,   support       Ring.     W.  41    Ringer's    solution    was    re- 
the  horns  of  the  uterus  on  soft       |>laced  by  adrenalin  solution,  r  :  1,000.000. 
threads.     Ligature  the   vagina       Time  trace,  half-minutes. 
before  cutting  through   it,  and 

cut  below  the  ligature,  which  can  then  be  used  to  manipulate  the 
uterus.  Do  not  pinch  the  utenis  wth  forceps,  and  handle  it  as  little 
as  possible.  At  once  place  it  in  Ringer's  solution  (p.  iq8),  kept  at  bodv 
temperature  (38°  C.)  in  a  small  beaker  immersed  in  a  water-bath  as  in 
the  experiment  on  the  contraction  of  isolated  intestine  (p.  446)  'cut  a 
ring  of  tissue  about  4  centimetres  in  widtli  from  one  of  the  horns  Tie 
a  loop  with  a  fine  sUk  thread  at  each  end  of  a  diameter  of  the  rin" 


1 102  REPROD  UCTION 

pinching  up  a  little  of  the  external  coat  to  do  so  with  fine  forceps. 
Make  the  arrangements  necessary  for  recording  contractions  of  the 
ring  while  it  is  immersed  in  a  glass  cylinder  in  the  bath,  as  in  Experi- 
ment I,  p.  446,  but  do  not  divide  the  ring.  Connect  the  segment  to  a 
lever,  as  in  that  experiment,  and  make  all  the  arrangements  mentioned 
there.  After  a  longer  or  shorter  interval  spontaneous  rhythmical  con- 
ti actions  of  the  uterus  ring  commence.  As  soon  as  they  are  well  estab- 
lished, and  while  the  contractions  are  being  recorded  on  a  very  slow 
drum,' replace  the  Ringer's  solution  by  serum,  defibrinated  blood,  blood 


Fig.  467.— At  1 1  Ringer's  solution  was  replaced  by  citrate  plasma.  At  39  Ringer's  solu- 
tion was  replaced  by  hirudin  plasma;  at  41  by  the  corresponding  hirudin  serum. 

prevented  from  coagulating  by  citrate  solution  (p.  66),  or  hirudin,  or  by 
plasma  and  note  the  effect.  Wash  away  the  serum  or  plasma  thor- 
oughly with  Ringer's  solution.  Replace  the  Ringer's  solution  by 
adrenalin  solution  (i  :  1,000,000).  Note  whether  the  tone  of  the  rmg 
(as  shown  by  its  permanent  shortening)  or  the  rate  and  strength  of  the 
contractions  are  increased.  While  a  tracing  is  being  taken  repeat  the 
observation,  adding  a  larger  proportion  of  adrenalm.  Determme  m 
what  concentration  a  distinct  effect  is  produced.  A  sufficient  number  of 
uterus  rings  can  be  obtained  from  one  animal  for  a  considerable  number 
of  experiments. 


Al'PENDIX 


COMPARISON  OF  METRICAL  WITH  ENGLISH  MEASURES. 


Measures  oj  Length. 

I  millimetre  =0*03937    inch. 

I  centimetre  =0-39 571 

1  decimetre  =  3*  93708  inches. 

I  metre  =39*37079     .. 

I  inch  =  25'3995  millimetres. 

Measures  of  Weight. 

I  gramme  =  15-432349  grains. 

I   kilogramme     =  2'20462i3  pounds. 

1   ounce  =  28'3495  grammes. 

I   pound  =453-5926 

Aleusures  of  Volume. 

I  cubic  centimetre=  0-061027  cubic  inch. 

I  litre   (i,ooo  cubic  centimetres)   =  6i-027032  cubic  inches. 

=  I '760  7  73      English      or      2'ii 
American  pints. 

=  0-22009668  gallon. 

I  cubic  inch  =  16-3861759  cubic  centimetres. 

I  cubic  foot  =28-3153119  cubic  decimetres  (or  litres). 

1   pint  =0-567932  litre. 

I  gaUon  =  4-5434579  litres. 

Measures  of  Work. 

I   kilogrammetre  =  about  7-24  foot-pounds. 

1   foot-pound  =0-1381  kilogrammctro. 

I   (kilo)calorie  of  heat  =  425-5  kilogrammetrcs  of  work. 

Temperature  Scales. — To  convert  degrees  Fahrenheit  int£)  degrees 
Centigrade,  subtract  32,  and  nuiltiply  the  remainder  by  g.  To  convert 
degrees  C.  into  degrees  F.,  multiply  by  l,  and  add  32  to  tJic  result. 

I  lO^ 


INDEX 


*,*  References  to  the  Practical  Exercises  are  in  black  figures. 


Abdominal  breathing,  228 

muscles  in  expiration,  228 
Abducens,  or  sixth  nerve,  897 
Aberration,  chromatic,  987,  1063 

spherical,  987,  1063 
Absorption,  420 

and  lipoid  solubility,  431 

coefficient  of  gases,  246 

comparative,  physiology  of,  425 

factors  concerned  in,  429 

from  the  peritoneal  cavity,  433 

from  the  stomach,  427,  446 

gas  exchange  in  intestine,  430 

in  different  animals,  425 

in  large  intestine,  445 

intra-  and  inter-epithelial,  440 

of  bile-constituents  in  jaundice,  378 

of  cane-sugar,  429,  446 

of  carbo-hydrates,  439 

of  fat,  path  of.  437,  458 

of  gases  in  blood,  246 

of  iron,  441 

of  light,  972 

of  osmosis  and  diffusion  in,  429 

of  parenteral.  440 

of  proteins,  441 

of  the  food,  425 

physical  introduction  to,  420 
theories  of,  427-430 

of  water  and  salts,  440,  416 
Acapnia  and  blood-pressure,  182 

and  mountain  sickness,  292 

and  shock,  190 
Acceleration  of  heart  by  sipping  water, 

169, 208 
Accelerator  nerves  of  heart,   157,   160, 

164,  197 
Accessory  auditory  nucleus,  899 

vagus  nucleus,  900 
Accommodation,  980 

mechanism  of,  982 

pupil  in,  983 
Acerebral  tonus,  911.  922 
Acetaldehyde,  536,  553 
Acetone,  553 

and  katabolism  of  fatty  acids,  559 


Acetone  in  diabetes,  521,  546 

in  urine,  521 
Aceto-acetic  acid,  553,  55S 

in  diabetes,  546 
A.C.E.  mixture,  63,  213 
Acetic  acid,  547 
Acid  albumin,  346,  452 
Acidity  of  gastric  juice,  343,  411 
Acrolein,  12 
Action  currents,  796,  804,  814 

and  functional  acti\  ity,  802 

diphasic,  798 

double  conduction  of,  766 

electromotive  force  of,  800 

in  polarized  nerves,  804 

in  voluntary  contraction,  736 

monophasic,  798 

of  central  nervous  system,  810 

of  eye,  811 

of  glands,  810 

of    heart,    88,    799,    806,    809, 
816 

of  muscle,  796,  816 

of  phrenic  nerves,  800 

of  spinal  cord,  766,  810,  867 

of  vagus,  801 

of  veratrinized  muscles,  802 

propagation  of,  797 

rate  of  propagation  of  varia- 
tion, 800 

reflex,  885 

of  skin,  810 

theories  of,  801 
Adamkiewicz's  reaction  of  protein,  8 
Adaptation  of  digestive  juices  to  food. 
362,  392,  398,  403, 407 
of  retina,  1007,  1018 
Addison's  disease  and  adrenals,  637 
Adenin,  582 

Adequate  stimuli,  873,  967 
Adipocere,  555 
Adiposophilia,  560 
Adrenal  bodies,  637 

relation  of,  to  coagulation,  45 

secretory  nerves  of,  640 
cortex,  functioa  of,  644 
104 


INDEX 


ti05 


Adrenalin,  action  of,  o  i  artery  rings,  66, 
214 
or  roagulalion  time,  639 
on  heart,  638 
on  nerve-endings,  180 
on  pupfl.  639 
on  sympatlietic.  965 
on  vaso-motors,  173,  177,  638 
on  veins,  179 
action  of  small  doses  of,  642 
arterio-sclerosis,  642 
artificial,  643 
assay  of,  639 
biological  tests  for,  639 
chemistry  of,  643 
formation  of,  643 
function  of,  640 
glycosuria.  541 

secretory   influence    of   nerves    on, 
640 
Adsorption,  424 
Aerotonometer,  256 
itsthesiometer,  compasses,  1072 
Frey's,  1040 
hair,  1040,  1071 
Afferent  impulses,  decussation  of,  866 
paths,  864 

scheme  of,  852 
Aftei-brain  (myelencephalon),  822 
After-images,  1015. 1069 
Agglutination,  30,71 

by  foreign  serum,  71 
Agglutinogens,  31 
Agraphia,  935 
Alanin,  2,  354 

formation  of  dextrose  from,  530 
Alanyl-tyrosyl-glycin,  443 
Albinos,  intravascular  clotting  in.  43 
Albuminates  or  derived  albumins.  9 
Albuminoids.  2,  543 
Albumins,  2,9 

heat-coagulation  of,  9 
in  urine,  483,  492,  494.  516-518 
Albumoses,  3 

action  of,  on  blood-pressure,  171,213 

on  coagulation,  37.  45 
in  peptic  digestion.  346 
tests  for.  in  urine,  516 
Albumosuria,  517 
Alcohol.  618 

action  of.  on  respiratory  centre,  189 

on  gastric  secretion,  618 
in  diet,  618 
poisoning,  blood-pressure  curve  in, 

189 
precipitation  of  proteins  by,  8 
Alcohols,  relation  of,  to  carbohydrates.  3 
Aldehydase,  268 
Aldehyde  groups  in  living  protein.  529, 

552 
Aldehydes,    relation    of.    to    carbo-hy- 
drates, 3,  552 


Aldohexoses,  529 

Aldol.  553 

Algomcter  ,  1049 

Alimentary  canal,  anatomy  of,  312 
length  of,  313 

time  of  passage  through,  328 
glycosuria,  532,  691 

Alkali-albumin,  10,  455 

Alkalinity  ol  blood,  etc.,  titratable,  25 

Alkaptonuria.  477,  572 

Allantoin,  excretion  of,  586 

Allantois,  1084 

'  All-or-nothing  '  law,  154 

Alloxuric  bodies,  475 

Alveolar  air,  partial  pressure  of  gases  in, 
261 

Amblyopia  after  occipital  lesion,  932 

Amboceptors,  28,73 

Amide-nitrogen  in  proteolysis,  354 

Amino-acetic  acid,  2 

Amino-acids,  i,  346,  353,  403 
absorption  of.  443,  444 
chemical  nomenclature  of,  353 
conversion   of,    into  glycogen    and 

dextrose,  346,  530 
formation  of,  from  tissuc-proteins, 

569 
of  urea  from,  573,  574,  612 
in  blood,  565 
in  liver  diseases,  574 
in  phosphorus  poisoning,  554 
in  urine,  475,  483 
metabolism  of,  572 
synthesis  of,  by  bactetia,  606 
Amino-bodies,  deamidization  of,  578 
Amino-succinic  acid.  354 
Amino-valerianic  acid.  354 
Ammonia,  action  of,  on  muscle  and  nerve, 
712. 733 
impermeability  of  lungs  for.  240 
in  proteolysis.  354 
in  the  blood,  source  of,  578 
in  urine.  513 

after  Ecks  fistula,  502 
reflex  inhibition  of  heart  by,   168, 
211 
Ammonium    salts,    formation    of    urea 
from.  574.  578 
sulphate,  precipitation  of  proteins 
by.  8,  517 
Amnesia.  935 
Amnion.  1084 
.Amniotic  fluid.  1084,  1090 
Amtt'ba.  6,  382.  627 
Ama?boid  movements,  16.  17.  706 
Ampere.  608 
Amylase.  33S 

pancreatic,  352.  356 
salivary.  356 
Ainyl  nitrite,  action  on  )nilse.  106 

formation    of    metha>moglobiii 
by.  53 

70 


lioC 


INDEX 


Araylolytic  stage  of   gastric  digestion. 

340,  343, 411 
Amylopsin,  352,  356,455 

influence  of  bile  on,  363 
Anabolic  changes  in  living  matter,  6 
Anacrotic  pulse,  106 
Anaesthesia  by  A.C.E.  mixture,  63 
by  chloral,  216 
by  chloroform  (Grehant's  method) 

200 
by  morphia,  63,  199 
by  pressure  on  brain,  945 
for  animals,  63 
Analyl-glyeyl-tyrosin,  443 
Anaphylaxis,  32 
Anastomosis  of  nerves,  940 
Anelectrotonus,  760,817 
Angular  gyrus  and  vision,  932 
Animal  board,  199,  212 
Animals,  localization  in,  945 

heat,  748 
Anions,  423 
Ankle-clonus,  887-889 
Annulus   of   Vieussens,    157,    161,    177. 

203,  204 
Anode,  423,  697 
Anterior  commissure,  893 
horn,  cells  of,  836,  848 

connections  of,  848 
roots,  848 
Antero-lateral  ascending  tract,  838,  845, 
858 
connections  of,  848 
descending  tract,  839,  845 

connections  of,  856 
ground  bundle,  839 
Antibodies,  31,  337 
Antidiabetic  diet,  546 
'Antidromic'  nerve  impulses,  179,  766, 

780 
Antiferments,  337,  384 

in  intestiail  parasites,  384 
Antigens,  31 
Antikinase,  44,  385 
Antilytic  secretion,  392 
Antimony  and  protein  metabolism,  554 
Antiperistalsis,  324,  326,  415 
Antipyretics,  678 
Antiseptics  for  operations,  215 
Antithrombin,  38,  39,  42,  44 
Antitrypsin,  337,  361,  384 
Antrum  pylori,  320,  321 
Aorta,  effect  of  compression  of,  202 
Aortic  insufficiency,  effect  of,  on  pulse, 
106 
notch,  96 

stenosis,  effect  of,  on  pulse,  107 
valves,  87,  96,  204 

and  dicrotic  wave,  104 
Apex-beat,  90,  193,  195 
Apex  preparation  of  heart,  143, 192 
Aphasia,  934 


Apl^asia,  Broca's,  935 

motor,  935 
sensory,  935,  937 
subcortical,  937 
temporary,  937 
Wernicke's,  936 
Aphemia,  936 
Apnoea,  277,  294 

production  of,  294 
vagi,  277 
vera,  277 
Apocodeine,  action  of,  on  vaso-moton?. 

171 
Appetite,  1056 
Aqueduct  of  Sylvius,  846 
Aqueous  humour,  58 

composition  of,  460 
Arachnoid,  833 
Arachnolysin,  action  of,  on  erythrocytes, 

28 
Arcuate  fibres,  internal,  845 
Arginase,  102 
Arginin,  354,  577 
Argyll-Roberston  pupil,  985 
Arhythmia,  respiiatory,  287 
Aromatic  sulphates  in  urine,  478.  510 
Arsenic  and  protein  metabolism,  554 
Arterial  blood-pressure,  amount  of,  112 
Arteries,  blood-pressure  pulse  in,  109 
structure  of,  82 
to  insert  cannulas  into,  63 
tone  of,  183,  889 
Artery  rings,  action  of  adrenalin  on,  214 

action  of  serum  on,  46 
Arterioles,  resistance  in,  129 
Arteriosclerosis,  velocity  of  pulse  in,  109 
Artificial  respiration,  200,  229 

with  oxygen,  202 
Ascending  degeneration,  859 
Aspartic  acid,  354 
Asphyxia,  176,  276 

condition  of  haemoglobin  in,  51 
effect  of,  on  circulation,  170, 211 
glycosuria  caused  by,  539 
in  the  foetus,  1093 
influence  of,  on  blood-pressure,  211 
Association  areas,  938 
centres,  928,  938 
fibres,  855.857 
Astatic  system  of  magnets,  700 
Asthma,  spasmodic,  and  bronchial  mus- 
cles. 280 
Astigmatism,  irregular.  988 

regular.  991,  1062 
Astrospheres.  1079 
Atrio-ventricular  bundle.    See  Auriculo- 

ventricular  bundle 
Atropine,  action  of,  on  heart,  164, 197 
on  nerve-cells,  180 
on  pupil,  986 

on  salivary  secretion,  386,  390, 
451 


INDEX 


1107 


Attraction  sphere,  5,  823,  1079 

in  nerve-cells,  823 
Auditory  centre,  899,  932 
nerve,  898,  903 

cochlear  division  of,  899 
vestibular  branch  of,  899 
ossicles,  1025,  1029 
path,  scheme  of,  898 
Auerbach's  plexus,  323,  324 
Augmentation  of  heart-beat,   157,  i70' 
204 
nature  of,  165 
primary,  159 
secondary,  159 
Augmentor  nerves,  effect  of,  on  quiescent 

heart,  166 
Aura,  937 
Auricular  canal,  8i 
fibrillation,  151 
flutter,  151 
pressure  curve,  98 
Auriculo-ventricular    bundle,    81,    135, 
138, 147 
pulse-tracings  in  disease  of,  149 
junction,  stimulation  of,  196 
node,  81,  147 
valves,  89,  204 

moment  of  opening  of,  96 
Auscultation  of  breath-sounds,  298 
of  heart-sounds,  205 
of  lungs,  298 
Auto-digestion  of  stomach,  382, 459 
Autogenetic  theory  of  nerve  regenera- 
tion, 776 
Autolysis,  569 

Automatic  actions  of  spinal  cord,  888 
Autonomic  nervous  system,  864,  963 

functions  of,  965 
Avalanche  theory,  959 
Axial  strand  fibrils,  775 
Axis-cylinder  or  axon,  755,  846,  854'^ 
bifurcation  of,  776 
fibrils  in,  823 
Axon-reflexes,  394,  776.  824 

Babinski's  sign,  887 

Bacteria  and  digestion,  415,  416 

in  faeces,  419 

in  intestine,  337,  416 

synthesis  of  amino-acids  by,  606 
Bactericidal  action  of  gastric  juice.  351 
Balloon  ascents,  deaths  in.  292 
Baryta,  absorption  of  cau'bon  dioxide  by, 

239 
Basal  ganglia,  903 
Basilar  membrane,  1027,  1032 
Bat's  wing,  contractile  vessels  of,  81, 178 
Batteries,  195,  697 
Beats  (hearing).  1070 
Beaumont  on  di^;cstion,  343 
Bcciitcrew's  nucleus.  899 
Bcckmann's  apparatus,  421,521 


.  cii<^u&  recorder,  296 

Bell's  expciiiiiciiis  on  nerve-rools,  863 

Belt  recorder  for  respiration,  232 

Benzoic  acid,  516 

Beri-beri  caused  by  polished  rice,  620 

thymus  in,  620 
Bert  on  double  conduction  in  nerves,  766 
on  effects  of  oxygen  at  high  pres- 
sure, 291 
Bctz  cells.  820.  847 
Bichromate  cell,  196 
Bidder's  ganglia,  141 
Bile,  357,  363 

absorption  of,  378,  406 
acids,  359'  456 

circulation  of,  406 
formation  of,  378 
Hay's  test  for,  456 
Pettenkofer's  reaction,  456 
test  for,  360 
adaptation  of,  to  food,  407 
and  absorption  of  fat,  363 
and     pancreatic     juice,     adjuvant 

action  of,  361 
and  surface  tension,  363 
as  an  excretion,  419 
circulation  of,  406 
composition  of,  357 
curve  of  secretion  of,  407 
digestive  functions  of,  361 
formation  of,  378 
freezing-point  of,  381 
gases  of,  264,  360 
in  emulsification  of  fats,  361 
influence  of  nerves  on  secretion  of, 

406 
inhibition  of  heart  by.  170 
mucin,  360,  405 
pigments,  358,  379,  456 
circulation  of,  406 
Gmelin's  test  for,  359,456 
production  of,  in  liver.  379 
relation  of,  to  spleen.  650 
precipitation  of  gastric  digest  by. 

364 
quantity  of,  361 
rate  of  secretion  of,  407.  413 
reactions  of.  456 
reinforcing  action  of,  363 
salts,  359 

action  of.  on  blood,  28.  70 
decomposition  of,  359 
Hay's  test,  520 

influence    of,    on    secretion    of 
bile.  407 
secretion  of,  influence  of  nerves  on, 
405 
influence  of  secretin  on,  406 
secretory  pressure  of,  408 
spectrum  of.  359 
Biliary  fistula,  363,  406 
Bilirubin,  358 


lio8 


INDEX 


Biliverdin,  358 

Bioplasm.     See  Protoplasm,  and  Living 

matter 
Bipolar  ganglion  cells,  828 
Bird's  blood,  coagulation  of,  36,  43 
Biuret  reaction,  8,  453 
Bladder,  503 

pressure  in,  in  micturition,  503 
Blastoderm,  1081 
Blind  spot,  1004,  1064 

mapping  the,  1064 
Blood,  bird's,  36 

carbon  dioxide  content  of,  26,  253 
chemical  composition  of,  47 
circulation  of,  80 
coagulation  of,  62,  33 
composition  of,  49 
•corpuscles,   coloured,    composition 
of,  50 
osmotic  resistance  of,  73 
crenation  of,  16 
destruction  of,  21 
dextrose  in,  50 
enumeration  of,  18,  67 
formation  of,  in  embryo,  20 
gaseous  metabolism  of,  250 
graveyard  of,  22 
life-history  of,  20 
osmotic  resistance  of,  73 
pernicious  anaemia,  21 
red,  15 

destruction  of,  21 
origin  of,  20 
rouleaux  formation  of,  16 
shadows  or  ghosts  of,  70 
size  of,  15 
structure  of,  15 
white.     See  Leucocytes 
distribution  of,  56,  187 

carbon  dioxide  in,  253 
electrical  conductivity  of,  26,  68 
flow,  calorimetric  method  of  mea- 
suring, 122 
in  different  organs,  127 
in  feet,  127 
in  hands,  126 

measurement  of,  218 
functions  of,  59 
gases  of,  244,  264,  360 

estimation  by  ferricyanidc,  249 
quantity  of,  249 
tension  of,  256 
results,  259 
guaiacum  test  for,  76 
kinetic  and  potential  energy  of  cir- 
culating, 119 
taking  of,  70 
living  test-tube,  34 
measurement  of  velocity  of,  120-124 
morphology  of,  14 
opacity  of,  70 
pigment,  microscopic  test  for,  78 


Blood  pigment,  preparation  of,  73 
plasma,  proteins  of,  563 

relative  volume  of,  68 
plates,  18 
platelets  and  copulation,  39,  40 

anticoagulants    and    preserva. 
tion  of,  40 

disintegration  of,  40 

functions  of,  62 
precipitin  test  for,  31 
quantity  of,  55 

in  lungs,  224 

which  may  be  lost,  189 
reaction  of,  62,  24 
regeneration  of,  22 
relative  volumes  of  corpuscles    and 

plasma,  27 
serum,    electrical     conductivity    of, 
380 

freezing-point  of,  380 
specific  gravity  of,  62,  26 
substances,  314 
sugar  in,  525, 494, 532, 538 
temperature  of,  684 
testing  for  adrenalin  in,  640,  641 
tests  for,  45-47 
titratable  alkalinity,  25 
vaso-constrictor  property  of  shed. 

45 
velocity  of,  1 17-127 

in  arteries,  119,  125 

in  capillaries,  120,  130 

in  v^eins,  120,  134 

measurement  of,  120,  122,  218 
vessels,  suturing,  iioo 
viscosity  of,  497,  23 
volume  of  corpuscles  and  plasma, 

27,  68 
why  it  does  not  clot  in  the  vessels, 

45 
Blood -pressure,  arterial  measurement  of, 
107 
and  acapnia,  182 

curves  with  elastic  manometers,  93, 

III 

with     mercurial     manometers, 

no,  112,  209 

effect  of  changes  of  posture  on,  188 

of  extracts  of  bone-marrow  on, 

182 
of  freezing  the  cord  on,  182 
of  haemorrhage  and  transfusion 

on, 212 
of  kidney  on,  649 
of  muscular  exercise  on,   115, 

211 
of  nervous  tissue  on,  650 
of  peptone  on,  213 
of  pituitary  on,  646 
of  suprarenal  on,  214 
of  testicle  on,  628 
of  thymus  on,  631 


INDEX 


1 109 


Blood -pressure,   estimation  of    the    ar- 
terial.2II 
factors  whicli  maintain,  116 
fall  of,  in  sleep,  950 
hydrostatic  and  hydrodynamic  ele- 
ments, 188 
in  capillaries,  130,  131 
influence  of   position   of   body  on, 
211 
of  proteoses  on.  213 
of  respiration  on,  283 
in  man,  influence  of  exercise  on,  115 
measurement    of.    by    stetho- 
scope, 113 
in  pulmonary  artery,  116 
in  right  and  left  ventricles,  116,  138 
mean  arterial,  109,  112 
measurement  of,  109,  211 
permanent  element  in,  in 
systolic  and  diastolic,  113 
tracings,  163,  208 
Blood-pump,  248 

Blood-serum,  freezing-point  of,  380 
Blood-supply,  regulation  of,  187 
Bloodvessels,  anastomosis  of,  1099 

rhythmically  contractile,  81, 173, 178 
structure  of,  82 
suturing,  iioo 
tone  of,  959 
Body,  composition  of,  590 
Bohr,  on  composition  of  blood-gases,  256 
Bolometer,  657,  756 

Bone-marrow  and  blood-formation,  20, 
22 
action  of  extracts  of,  649 
Bones,  composition  of,  609 

influence  of  pituitary  on,  648 
of  testicles  on.  628 
'  Boot '  electrodes,  814 
/3-oxybutyric  acid,  553 
Brain,  anaemia  of,  950 
chemistry  of,  955 
circulation  in,  952 
condition  of,  isolated,  940 

in  sleep,  949 
development  of,  821 
functions  of,  903 
heat-production  in,  664 
influence  of,  on  spinal  reflexes,  882 
respiratory  changes  in   volume  of. 

289 
resuscitation  oi,  953.  954 
si/e  of,  at  different  ages,  952 

and  intelligence,  952 
temperature  of,  686 
volume,   respiratory   variations  in, 
289 
Bread,  693 

Breast-feeding,  superiority  of,  1096 
Breath,  holding,  233 
Broca's  area.  936,  939 
aphasia,  935 


Bronchi,  222 

movements  of,  in  respiration.  230 

nerves  of,  280 
Bronchial  breathing,  231 

muscles,  innervation  of.  280 
Bronchoscope.  230 
Brownian  motion,  448 
Hn  >wn-Sequard's  syndrome.  866 
Brunner's  glands,  374.  377 
'  Bully  coat,'  39 

Burdach's  column,  connections  of,  842 
See  Posterior  median  column 

tract,  838 
Burdon-Sanderson  on  negative  variation, 

799, 800 
Burns,  superficial,  death  from,  293 
Buttermilk  diet,  417 
Butyric  acid,  553 

fermentation.  418 

Cachexia  strum ipriva,  633 
Caecum,  nerves  of,  326 
Caffeine,  619 

as  diuretic,  502 
Caisson  disease,  291 
Calcium  and  bone  formation,  609 

deficiency  of,  609 

relation    of,    to    heart-beat,    152. 
198 
Calorimeter,  air.  654,  655 

differential  micro-.  656 

respiration,  239,  653,  694 
Atwater's.  654 

water  equivalent  of,  694 
Calorimetric  method  for  blood-flow  in 
hands,  218 
for  vaso-motor  leflexes,  186 
Calorimetry,  651,  652,694 
Campbell,  visuo-psychic  area  of,  932 
Cancer,  gastric  juice  in,  350 
Cane-sugar,    absorption    of,    439,    429, 

458 

inversion  of,  10,  333 

by  gastric  juice,  350 

tests  for,  II 
Cannula,  three-way,  210 

gastiic,  453 

to  put  into  an  artery,  63 
trachea,  199 
vein,  213 
Capillaries,  blood-pressure  in,  131 

changes  of  calibre  of,  171 

circulation  in,  120,  129.  190 

pulse  in,  131 

resistance  in.  120,  130 

total  cross-section  of,  130 

velocity  of  blood  in,  130 
Capillary  electrometer.  702,  703.  800 
Caproic  acid.  557 

Capsule,  internal.    See  Internal  capsule 
Carbo-hydrates,  absorption  of.  439 

amount  of,  in  standard  diet,  611 


INDEX 


Carbo-liydrates,  composition  of,  i,  3 
constitution  of,  3 
intermediary,  metabolism  of,  534 

in  diabetes,  544 
mcttabolism  of,  525 
Mulisch's  test  for,  11 
necessity  of,  in  nutrition,  596 
passage  of,  through  placenta,  1087 
protein-sparing  action  of,  595 
reactions  of,  10 
tests  for,  10 
Carbon  balance-sheet,  606 
equilibrium,  606 
dioxide,   action  of,   on  respiratory 
centre,  276 
and  blood-flow  in  heait,  176 
distribution  in  blood,  253 
estimation  of,  239,  250,  299 
excretion,    influence    of   forced 
respiration  on,  244 
mechanism  of,  262 
in  alveolar  air,  239 
in  blood,  condition  of,  255 
in  different  animals,  243 
in  foetal  blood,  1085 
influence  on  haemoglobin,  253 
in  serum,  254,  255 
in   venous    blood,    tension    of, 

260 
partial  pressure  of,  in  alveoli, 
261 
in  blood,  257 
in  tissues  and  liquids, 
260 
production,  Haldane's  appara- 
tus for  measuring,  298 
production     of,     in     different 
animals,  243 
in  homoiothermal  animals, 

243 
in  muscular  work,  241 
in  poikilothermal  animals, 

243 
in  relation  to  body-weight, 

242 
in  rigor,  242,  751 
tension  of,  in  tissues,  264 
washing  out  of,  277 
monoxide,  method  for  quantity  of 

blood,  56 
necessary  quantity  in  diet,  613 
Carbonic  acid  and  urea  formation,  579 

oxide  haimoglobin,  53,74 
Cardiac  cycle,  85 
death,  169 
impulse,  90, 206 
nerves,  157,  194,  196 
sound, 96 
sphincter,  314 
Cardio-augmentor  centre,  167 
Caidiogram,  91,  205 
inversion  of,  9 1 


Cardiograph,  90,  206 
Cardio-inhibitory  and  augmentorcentres, 
16'' 
tone  of,  167 
Cardiometer,  139 
Cardiophonogram,  88 
Cardiopneumatic  movements,  128,  297 
Carnosin  in  muscle,  742 
Casein,  348 

as  adequate  protein,  603 
Caseinogen,  348,  692 
Castration,  effects  of,  626 
Catalase,  76,  267 
Catalysers,  333,  335 
Catheterism,690 
Catheter,  pulmonary,  257 
Cells,  structure  of,  4 
Cellulose,  digestion  of,  417 
Central  canal  of  cord,  821,  833 
grey  axis,  833 

nervous  system,  action  currents  of, 
810 
arrangement  of  white  and 

grey  matter  in,  833 
development  of,  821 
functions  of,  859 
general     arrangement     of, 

833 
histological    elements    of, 

822, 833 
localization  of  function  in, 

940 
methods  of  study  of,  820 
structure  of,  819 
Centre  for  smell,  933 
for  taste,  934 
of  gravity  of  body,  913 
thumb,  938 
Centres,  cardio-inhibitory  and  augmen- 
tor,  167 
heat,  675 

'  motor,'  of  cortex,  918 
musical,  933 
of  cord  and  bulb,  890 
sensory,  of  cortex,  931,  934 
vaso-motor,  180,  182 
Centrifuge,  64 
Centrosome,  5,  823 

in  the  ovum,  1079 
Cerebellar  ataxia,  906 
Cerebellum,  anatomical  division  of,  911 
connections  of,  857,  906 
functions  of,  904 
inferior  peduncle  of,  857 
localization  of  function  in,  911 
middle  peduncle  of,  85  s 
peduncles  of,  857 
structure  of,  911 
superior  peduncle  of,  858 
worm  of,  846,  857,  911 
Cerebral  anajmia,  188,  950 

stimulation  of  vagus  after,  185 


INDEX 


Cerebral  circulation.  953 

cortex,  and  respiration,  270 

clinical  and  pathological  obser< 

vatiuns  on,  928 
development  of,  834 
functions  of,  914 
histological   dilferentiation    of, 

924 
inhibition  from,  921 
layers  of,  924 

localization  of  function  in,  91 « 
'  motor  '  areas  of,  918 
sensory  areas  of.  931 
stability  of  reactions  of,  920 
hemispheres,  excision  of,  961 
frog,  961 
pigeon,  961 
localization,  Flechsig's  areas,  925 
peduncle,  854 
vesicles.  821 
Cerebrins,  768 
Cerebro-spinal  fluid.  58,  460,  956 

displacement  uf,  289 
Cerebrum,  effects  of  removal  of.  915 
Cervical  sympathetic.    Se^t;  Sympathetic, 

cervical,  215 
Chalk-stones.  580 
Cheese,  614,  692 
'  Chemical  tone.'  670 
Chemiotaxis,  (>i 

in  nerve  regeneration.  774 
Chemistry  of  nervous  activity,  955 
Cheyne-Stokes  respiration,  281,  294 
Chiasma,  optic,  894 
Child,  food  requirement  of,  616 

gaseous  exchange  in,  242 
Chloral,  anaesthesia  by,  i8S.  211 
Chlorides,  estimation  of,  508 
Chloroform  ancusthesia,  inhibition  in,  168 
passage  of.  through  placenta,  1086 
Cholesterin.  4.  47.  561.  768 
circulation  of.  562 
in  bile,  406 
or  cholesterol,  306 
reactions  of.  457 
Cholic  acid.  359 
Cholin,  4,  416.  562 
Cholohxmatin.  359 
Chorda  tympani,  177,  385,  387,  450 

stimulation  of,  450 
Chordo-lingual  triangle,  385 
Chorion,  1084 

Choroidal  epithelium,  976,  1008 
Chromaffin  cells.  643 
Chromatin,  5 

changes  in,  in  nerve-ccIls,  948 
extranuclear,  948 
Chromogen,  476 
t  hromophanes,  1009 
ChromosonifS,  6.  1081 
Chrysotoxin,   action   of.  on   bI(K)d -pres- 
sure, 171 


Chyle,  composition  of,  14,  58,  437 

fistula  in,  58 
Chyme.  320.  402,  413 

to  obtain  normal.  453 
Chymosin  (viJe  Kennin),  347 
Cilia,  707 

uiovenii-nts  of,  784 

work  done  by,  708 
Ciliary  ganglion,  895 

muscle.  895.  982 

nerves,  983 

processes.  974 

and  secretion  of   aqutous   hu 
mour,  976 
Cinematograph.  1002 
Circulating  blood,  microscopic  examina- 
tion cjf,  191 

liquids,  14 
Circulation,  changes  in.  at  birth,  1094 

comparative.  80 

cross,  through  brain,  278 

electrical  method,  135.  215 

general  view  of,  81 

Ik-ring's  method,  135 

in  brain,  953 

in  capillaries,  129,  131 

in  the  embryo,  1084 

in  the  frog's  web.  15, 191 

in  the  lungs  137, 223 

methylene  blue  method,  136.  215 

in  the  tadjwle,  191 

influence  of  postuie  on,  188 

of  lymph.  190 

time,   determination   of.    135,    137, 

215 

pulmonary,  672 
Circus  movements,  913 
Citrates  and  coagulation,  37 
Clarke's  column,  836 

connections  of,  844 
Coagulated  proteins,  leactions  of,  9 
Coagulation  of  blood,  42,62 

action  of  fluorides  on.  37 

of  citrates  on,  37 
birds.  36 
calcium  in,  36 
factors  in,  42 
hirudin  and,  37 
influence  of  platelets  in,  37 
of  proteoses  on,  37 
of  tissue  extracts  on,  36 
influences  restraining,  42 
int  aNascular,  42 
leech  extract  and.  38 
manganese  and,  37 
of  crayfish.  40 
of  Limulus.  40 
peptones  and,  37 
relation  of  adrenals  to,  45 

liver  to.  44 
siadied  with    ultraniicroscope. 
39 


INDEX 


Coagulation  of  lymph,  57 

temperature,  to  determine,  9 
Coagulins,  41 
Coal-gas  poisoning,  53,  74 
Cobra-venom  and  coagulation,  43 
Cocaine,  action  of,  on  nerves,  765 
on  pupil,  986 

fever,  678 
Cochlea,  898,  1027,  1028,  1029 
Cochlear  root  of  eighth  nerve,  846,  899 
Cocoa,  617,  619 
Co-enzymes,  337 
Co-ferment,  540 
Coifee,  619 
Cola-nut,  619 

Cold  sensations,  1041,  1042,  1043,  1044, 
1072 
after     section     of     cutaneous 

nerves,  1050 
paths  for,  868 
Collaterals,  755,  824 

of  posterior  root  fibres,  843 
Colon,  movements  of,  325 

innervation  of,  326 
Colostrum,  1095 
Colour,  body  and  surface,  972 

blindness,  1019,  1069 
temporary,  102 1 

mixing,  1012,  1068 

triangle,  1014 

vision,  ion 

Hering's  theory  of,  1017 
Young-Helmholtz's  theory   ol, 
1013 
Coloured  shadows,  1016 
Colours,  complementary,  1012,  1068 

primary,  1013 
Coma,  congestion  of  brain  in,  941 

diabetic,  546 
Comma  tract,  839,  843 
Commissural  fibres,  835 
Common  path,  principle  of  the,  871 
Commutator,  Pohl's,  706 
Compensator,  701 

Compensatory  pulse  of  heart,  155,  156 
Complement,  28,  72 
Complemental  air,  234,297 
Complementary  colours,  1012,  1068 
Condensed  air,  effects  of  breathing,  290 
Conduction,  doiTble,  in  nerve,  765 

irreciprocal,  766 

isolated,  law  of,  767 

loss  of  heat  by,  658 
Conductivity,  molecular,  423 

of  nerve,  760,  764 

anaesthetics  and,  787 
effect  of  temperature  on,  765 
electrical  currents  on,  816 

specific  electrolyte,  423 
Congo-red  as  test  for  acids,  345 
Conjugate  deviation,  931 
Conjugated  proteins,  2 


Conservation  of  energy,  law  of,  in  body. 

659 
Consonants,  307 

Contraction,  formula  of,  762,817 
for  nerves  in  si/u,  763 
law  of,  for  human  ner\es,  818 
paradoxical,  805,  816 
secondary,  805,814 
Contractions  of  isolated  uterine  rings, 
IIOI 
superposition  of,  789 
Contrast  (vision),  1016 
Co-ordination  of  movements,  913,  945 

of  reflexes,  880 
Core  models,  and  electrotonic  currents, 

803 
Cornea,  radius  of  curvature  of,  977 
Corona  radiata,  834,  847,  855 

path  from  cortex  in,  849 
Corpora  Arantii,  87 

quadrigemina  and  respiration,  270, 
846,  853,  903 
anterior,  894,  903 
posterior,  899,  903 
striata,  822,  842 

and     temperature     regulation, 
67-6,  834 
Corpuscles  and  plasma,  relative  volume, 

68.     See  Blood 
Corpus  callosum,  835,  855 
dentatum,  835 
luteum,  629,  1076,  1080 

and  menstruation,  1078 
hffimatoidin  in,  379 
internal  secretion  of,  629,  1078 
origin  of,  1078 
striatum,  842,  904 
Cortex  of  brain,  functions  of,  914 
'  motor  '  areas  of,  918 
sensory  areas  of,  931 
Corti,  ganglion  of,  898 

organ   of,    898,     1028,    1030,    1032, 
1034 
Cortical  epilepsy,  937 
grey  matter,  833 
Costal  breathing,  228 
Coughing,  282 

Cranial  conduction  of  sound,  1031, 1070 
nerves,  891 

bifurcation   of   afferent    fibres, 

893,  896,  897,  899 
homologies  of,  892 
nuclei  of,  891 
Crayfish  blood,  clotting  of,  40 
Cream,  691 
Crenation,  16 
Crista  acustica,  907 
Cross  circulation  through  brain,  278 
Crossed  pyramidal  tract,  838,  847,  851 

connections  of,  847 
Crowbar  case,  American,  939 
Crura  cerebri,  842,  846 


INDEX 


1113 


Crusta,  842 

CultivatioQ  of  tissues  outside  the  body. 

1097 
Cuneate  funiculus,  841 

nucleus,  841 

relation  of,  to  ftllct.  845 
Cuneus  and  vision,  932 
Cuosin,  562 
Curara,  180 

action  of.  on  gaseous  exchange,  243. 

533 
on  heat  production,  669.  676 
on  nerve -endings,  180 
on  skeletal  muscle,  712.784 
on  vomiting,  330 
Curdling  of  milk  by  rennin,   347,  348, 

453 
Current  intensity  and  stimulation,  714. 
760 
of  action.     See  Action  current 
of  rest.     See  Demarcation  current 
Cutaneous  burns,  death  from,  293 
excretion,  505 
nerves,  section  of.  1045 
respiration,  292 
sensations,  1038 

localization  of,  1052 
Trotter    and     Davies'    experi- 
ments, 1045 
Cybulski's     arrangement     (velocity    of 

blood),  123 
Cyclopoiesis,  604 
Cystein,  354,  359,  571.  572 
Cystei.iic  acid,  360 
Cystic  compounds,  604 
Cystinuria,  360.  482,  570 
Cytolysins,  31 
Cytoplasm,  5 
Cytosin,  582 

Dancing  mice,  labyrinth  in.  912 

Daniell  cell,  195,  697 

Daphnia,  action  of  muscarine  on.  164 

heart  of,  165 

Metchnikoff's  researches  on.  60 
Dark-adapted  eye,  1007,  1009,  ioi8 
Daturine,  action  of,  on  heart,  164 

on  pupil,  986 
'  Dead  space,'  respiratory.  235 
Deaf-mutes,  atrophy  of    temporal   con- 
voluticjus  in,  933 

equilil>ration  in.  909 
Decerebrate  rigidity,  911,  922 
Decidua,  1076,  1083 

absorption  of,  by  leucocytes,  60 

artificial  production  of,  1078 
Decinormal  solutions.  473.  514 
Decussation  of  afferent  impulses,  866 

of  efferent  impulses,  866 

of  fillet,  842 

of  optic  nerve,  894,  932 

of  pyramids.  841,  847.  850 


Decussation  of  sensory  paths,  866 
DefcBcation.  326 
Deliciency  diseases,  619 

phenomena,  860 
Degeneration  of  muscle,  777 
of  nerves,  769.  771 

cliemislry  of.  772 
of  spinal  roots.  771 
reaction  of,  777 
Deglutition,  316 
centre,  319 
nerves  of,  319 
sounds,  318 
Deiters'  nucleus,  856,  858,  865,  899 
Delirium  cordis,  151,203.     S««lMbrillaiy 

contraction,  203 
Demarcation  current,  79G.  814 

electromotive  force  of,  799 
theories  of.  801 
Dendrites,  824 

amceboid  movements  of,  824 
and  sleep,  950 
Dentate  nucleus,  835.  841,  858 

of  olive,  841 
Depressor  nerves,  168,  171,  183.  184 
pressor  action  of,  186 
refiex,  reversal  of.  876 

in  cerebral  anaemia.  186 
Descending  degeneration,  838, 847 
Deutero-proteose,  3,  10 
Development  of  embryo,  1083 
Dextrins,  3,  11,  341,689 

formed  in  salivary  digestion,  341, 

449 

tests  for,  II,  689 
Dextrose,  3,  47,  332.  517,  529 

estimation  of,  in  urine,  519 

in  blood,  47,  50,  440.  t94.  53* 

in  lymph,  440 

ratio  to  nitrogen,  543 

tests  for,  10,  483 

Trommer's  test  for,  10 
Diabetes,  538 

dextrose-nitrogen  ratio  in.  54a 

diet  in,  545 

duodenal,  626 

levulose  used  up  in,  532 

mellitus,  543 

oxygen  consumption  in,  241,  24a 

pancreatic,  538,  545.  622 

phlorhizin,  542. 691 

reaction  of  blood  in,  24 

respiratory  quotient  in,  241 

sugar-destroying  power  of  blood  in. 

545 
Diabetic  coma,  546 
Diapedesis,  61.  191 
Diaphragm  in  respiration,  225,  269 

recording  movements  of,  232 
Diastases,  87.  338,  378,  526 
Diastase,  salivary,  338 
Diastole  of  heart.  87 


III4 


INDEX 


Dichromatic  vision,  1020, 1069 
Dicrotic  wave  of  pulse,  104,  11 1 
Dietaries,  standard,  610,  615 
Dietetics,  610 
Diet  in  diabetes,  545 
Diffusion,  420 

circles,  981,  1022 
of  gases,  245 
Digestion  as  a  whole,  410 

and  absorption,  time  required  for, 

458 
bacteria  and,  415,  416 
changes  in  acidity  of  gastric  contents 

in,  412 
chemical  phenomena  of,  330,  368 
comparative,  312 
gaseous  exchange  during,  243 
heat-production  in,  687 
in  intestines,  412 
in  stomach,  410 
mechanical  phenomena  of,  315 
of  carbo-hydrates,  350,  410 
of  fats,  349,  357.453,457 
of  proteins,  411 
significance  of,  315 
time  required  for,  412, 458 
Digestive  glands,  microscopical  changes, 
368 
juices,  adaptation  of,  to  food,  363, 
392,  398,  404,  409 
process  of  formation  of,  377 
protection    of    mucous    mem- 
brane from,  383 
summary,  409,  410 
organs  in  different  animals,  312 
Digitalis,  diuretic  action  of,  502 
Dilator  of  pupil,  985 
Diopter,  981 
Diphasic  variations,  806 
Diphtheria  toxin,  action  of  enzymes  on, 

366 
Diplopia,  895,  997 

Direct  cerebellar  tract,  838,  844,  864 
connections  of,  844 
pyramidal  tract,  838,  847,  850 
Disaccharides,  3,  365 

absorption  of,  439 
Discharge  of  ventricle,  period  of,  87,  97 
Dispersion  in  eye,  988 
Distribution  of  oxygen  in  blood,  250 
Diuresis  by  salts,  496 
Diuretics,  502 
Doremus'  ureometer,  513 
Double  conduction  in  nerve,  766 
Dromograph,  122 
Dulcite,  3 
Duodenum,  digestion  in,  412 

glycosuria  after  removal  of,  626 
Dura  mater,  833 
Dyspnoea,  276 
heat,  296 
respiratory  quotient  in,  240 


uar,  anatomy  of,  1025 
ossicles  of,  1025 

functions  of,  1029 
resonance  tone  of,  89,  734 
Echidnase,  53 
Eck's  fistula,  379,  575 
Ectoderm,  6,  1081 
Ectoplasm,  4 
Edestin,  596 

tryptic  digestion  of,  355 
Effector  organs,  870 

Efferent  impulses,  decussation  of,  842, 
847,  850,  866 
paths  of,  865 
scheme  of,  862 
Egg-albumin,  absorption  of,  441 
aniino-acids  in,  i 
excretion  of,  442,  495,690 
reactions  of,  9 
Eggs,  iron  in,  610 
Ehrlich's  triacid  stain,  ly 
Eighth  nerve.     See  Auditory  nerve 
Elasticity  of  muscle,  709 
Electric  fishes,  812 

signal,  706 
Electrical  conductivity  of  blood,  26,  68 
of  gastric  juice,  381 
of  milk,  1095 
of  serum,  69,  380 
organ. 813 

response.    See  Action  current 
Electro-cardiogram,  human,  808 
Electrodes,  to  make,  781 

unpolarizable,  705,814 
Electrolytes,  422 
Electrometer,  701 

capillary,  702,  800 
Electromotive  force,  698,  800 
Electrons,  423 

Electrotonic  alterations  of  excitability 
and  conductivity,  759 
currents,  803,  816 
Electrotonus,  759,  816 
Emulsification,  12,  361 
Eleventh  nerve,  902 
Emboli,  artificial,  820 
Embrj'o    and    uterus,    connections   be" 
tween,  1083 
asphyxia  in,  1093 
circulation  in,  1083,  1095 
development  of,  1078.  1083 
formation  of  the,  1081 
gases  of  blood  in,  io85 
glycogen  in,  530,  1089 
heat-production  in,  109 1 
inverting  enzymes  in,  365 
liver  in,  1090 

metabolism  of,  1089,  1092 
physiology  of,  1083 
Emetics,  330,  453,  458 
Emmetropic  eye,  989 
Emotions,  genesis  of,  939 


INDEX 


ii'5 


Emulsin,  332,  334 
Eadocardiac  pressure.  92,  94 

amount  of,  in  ventricle.  92,  94 
curves  of.  93,  96.  97 
measurement  of,  93 
negative,  loi 
Endoderm,  6,  108 1 
Endo^nzymes,  331 
Endogenous  fibres  of  cord.  835,  839,  869 

metabolism  of  proteins.  564 
Endoplasm.  4 

Endothermic  reactions,  664 
Enemata.  324.  445 

Energy  of  food,  influence  of  hydrolysis 
on,  659 

law  of  conservation  of,  in  body.  659 
Engraitiiig,  1079 
Enterokinase.  366.  409 

nature  of,  367 
Enzymes.     See  Ferments 
Ependyma.  833 
Epiblast.     See  Ectoderm 
Epicritic  sensibility,  105 1 
Epiglottis.  317 
Epilepsy,  cortical.  937 

Jacksonian.  937 

produced  by  absinthe,  930 
Epinephrin,66,  171.     S««  Adienalin 
Equilibration  and  afferent   impressions 
from  muscles,  910 
from  skin.  910 

and   orientation,    afferent   impulses 
concerned  in.  907 

cerebellum  and,  905 

Deiters'  nucleus  and,  900 

in  dogfish.  908 

in  pigeon.  90S 

muscular  nerves  and.  910 

semicircular  canals  and.  899,  900, 
908 

skin  and.  910 
Erection  centre,  181 
Erepsin,  365 

Ergograph.  628,  724,  727. 786 
Ergot  and  blood-pressure,  171 
Erucic  acid.  547 
Erythroblasts,  21 

Erythrocytes.  15.    S«  Blood-corpuscles, 
red 

enumeration  of,  19,  67 

gases  of.  250,  «5i 

life-history  of,  20 
Erythrodextrin,  11.  341. 44^ 
Esbach's  method  of  estimating  albumin, 

517 

Eserine,  action  of,  on  accommodation, 
982 
on  pupil.  986 
Ether,  action  of.  on  bio  id -corpuscles.  28, 

29,  70 
Ethyl  butyrate.  synthesis  of.  by  lipase. 
332.  438 


Eudiometer,  248 
Euglobulin,  48 
Eustachian  tube.  291,  1025 

valve.  1088 
Evaporation,  loss  of  heat  by,  658 
Excitability,  a  property  of  living  matter, 
7 

and   conductivity,    voltaic   current 
and. 816 

direct,  of  muscle.  712. 784 

of  nerve,  effect  of  temperature  on, 
758. 764 
electrical  currents  on,  732, 
816 
Excitable  tissues,  the,  697 
Excretion,  469 

Exogenous  metabolism  of  proteins.  564 
Exothermic  reactions,  664 
Expectoration,  469 
Bxpiratiau,  223,  228 

duration  of,  233 

forced,  229 
Expired  air,  composition  of,  239. 298 
Extensibility  of  muscle,  709 
Extension  reflex,  crossed.  874.  960 
Extensor  reflex,  the,  872 

thrust,  the.  873 
Extero-ceptive  reflexes.  886 

fields.  886 
Extra  contraction  of  heart,  155 

systoles,  in  man.  155.  156 
Exudation,  inflammatory,  61 
Eye.  action  currents  of,  811 

artificial,  KUhne's.  1061 

chemistry  of  refractive  media,  976 

compound  of  insects.  973 

currents  of,  811 

defects  of,  987 

development  of,  822 

dissection  of,  1058 

extrinsic  muscles  of,  1023 

Kiihne's,  1061 

movements  of.  1022 

nerves  of.  983 

optical  constants.  977 

pupillo-constrictor  fit  ires,  1067 
dilator  fibres,  1067 

reduced.  979 

refraction  in,  977 

retinal  fatiguf.  1068 

visual  acuity,  1068 

structure  of,  974  •  1058 

Facial  nerve.  897 

union  of.  with  accessory.  941 

palsy.  897 
Facilitation  of  reflexes.  R81 
Fajces.  action  of  extracts  on,  418 

bacteria  in.  419 

composition  of.  418 

microscopic  al  examioatiou  of.  457 

odour  of.  4 1  'J 


Iii6 


INDEX 


Fasting  men,  metabolism  in,  593 

experiments,  1054 
Fat,  absorption  of,  435, 457 

influenced  by  bile,  363 
amount  of,  in  standard  diet,  611 
composition  of,  i 

formation  of,  from  carbo-hydrates, 
551 
protein,  553 
intermediary  metabolism  of.  556 
melting-point  of,  12 
metabolism  of,  547 
liver  and,  558 
migration  of,  548,  554,  559 

in  phosphorus  poisoning,  554 
mobilization  of,  556 
non-nutritive  function  of,  559 
passage  out  of,  intestinal  epithelium, 

436 
storing  of,  549 

synthesis  of,  in  intestinal  mucosse, 
437 
Fatigue,  changes  in  nerve-cells,  831 

influence  of,  on  muscular  contrac- 
tions, 723 
on  muscle-curve,  786 
muscular,  cause  of,  725 
of  muscle-nerve  preparation,  seat  of 

exhaustion  in,  786 
of  n&rve -cells,  947 
seats  of,  727 
Fats,  chemistry  of,  547 
constitution  of,  3 
tests  for,  II 
Fatty  acids,  absorption  of,  437 

and  glycogen  formation,  530 
decomposition  of,  in  body,  557 
formation    of,    from    carbo-hy- 
drate, 552 
synthesis  of,  to  fat,  438 
tests  for,  12 
Fechner's  law,  1057 
Fehling's  solution,  518 

Benedict's  modification  of,  519 
test  for  sugar,  517 
Ferment  action,  quantitative  action  of, 

447 

cellulose-dissolving,  417 

mode  of  action  of,  333,  335 

reversible  action  of,  332 
Fermentation,  butyric  acid,  418 

lactic  acid,  418 
Ferments,  330 

in  the  liver,  589 

intracellular,  331 
autolysis,  588 

list  of,  339 

specificity  of,  334 

quantitative  estimation  of,  336 
Fever,  aseptic,  681 

caused  by  cocain,  678 
by  xanthin,  681 


Fever,  cnanges  in  urine  in,  677 

derangement  of  heat  regulation  in, 
679 

metabolism  in,  680 

nervous,  682 

production  of  heat  in,  678 

'  puncture,'  676 

'  retention  theory,'  680 

significance  of,  682 

vaso-motors  in,  680 
Fibrillary  contraction,  151 
Fibrin-ferment.  34.     Sei?  Thrombin 

formation  of,  35 

preparation  of,  65 
Fibrinogen,  34 

production  of,  in  liver,  35 
Fibrino-globulin,  47 
Pick's  theorv  (vision),  loio 
Fillet,  846,  853 
Flavour,  1038 
Flechsig's  developmental  zones  or  centre, 

927 
Flexion  reflex,  960 
Flour,  692 
Flow  of  liquids,  with  intermittent  pres- 

sure,  85 
Fluoride  plasma,  clotting  of,  38 
Fluorides,    action    of,    on    coagulation, 

37,64 
Foetal  heart,  1091 
Folin's  method  of  estimating  ammonia, 

513 
indican,  511 
kreatinin,5i6 
urea,  511 
urid  acid,  515 
Food  substances,  314 
Foods,  isodynamic  relations  of,  747 
Foramen  of  Monro,  822 
Forced  movements,  912 
Fore  brain,  822 
Formaldehyde  reaction,  8 
Formatio  reticularis,  842 
Formic  acid,  547 
Formula    of    contraction.     See  Law  of 

contraction,  817 
Freezing-point,  determination  of,  521 
Frey's  aesthesiometer,  1040 
Frog,  heart  of,  anatomy,  191 
to  pith  a,  191 
vagus,  dissection  of,  194 
stimulation  of.  196 
web  of,  circulation  in,  191 
Function,  localization  of,  940 
Fundus  of  stomach,  320 
Funiculus  cuneatus,  841 
gracilis,  841 

Gall-bladder,  405,  413 

reflex  contraction  of,  406 
Gall-stone,  pain  caused  by,  873 
Galvani's  experiment,  814,  795 


INDEX 


II17 


Galvanometers,  '199 

string,  700,  800 
Ganglia  habenula;,  904 

of  posterior  roots,  development  of, 

»22 

Ganglion  cells,  sympathetic.  828 
spLrale,  898 
vestibulare,  898 
Gaskell's  method  (heart),  193 
Gas-pump,  248 

Gases,  absorption  coefficient  of,  246 
diffusion  of,  245 
of  blood,  244 

extraction  of,  248 
quantity  of,  249 
tension  of,  256 
of  muscle,  266 
partial  pressure  of,  246 
tension  of,  247 
in  tissues,  264 
Gasserian  ganglion,  development  of,  826 
Gastric  digestion,  rdle  of  HCl  in.  i.\7 
testing  for  products  of.  452 
glands,  influence  of  nerves  on,  395 

secretory  changes  in,  372 
juice,  343 

acidity  of,  344 
antiseptic  function  of,  350 
artificial,  452 
Beaumont's  work  on,  343 
chemistry  of,  344 
digestion  of  proteins  by.  345 
electrical  conductivity  of,  381 
freezing-point  of,  381 
hydrochloric  acid  of,  344 
in  cancer,  344 

influence  of  substances  on  se- 
cretion of,  397,  399 
lactic  acid  in,  345 
milk -curdling  action  of.  347 
psychical  secretion  of,  398 
to  obtain  pure.  455 
secretion,  398 
Gelatin  as  a  food,  603 
in  nerves,  769 
tests  for,  9 
Geminal  fibres,  851 
Geminules,  824 
Geniculate  bodies,  894 
Gianiizzi,  crescents  of,  369 
Gibbs.  thermodynamic  law,  425 
Glands,  action  currents  of,  810 

heat -production  in,  664 
Gliadin,  feeding  with,  605 
Globin,  54 

Globulins,  tests  for,  9 
Glomerulus,  function  of,  498 
Glosso-pharyngeal  nerve,  900 

and  taste,  896 
Glottis,  310 
Gluco-proteins,  2 
Glucose,  10 


Glutamic  or  glutaminic  acid,  354 
Glutaminic  acid.  566 
Glycerine,  i,  528 

formation  of,  from  carbo-hydrates, 
552 
of  glycogen  from,  529 

tests  for,  12 
Glycerose,  528 

Glyceryl-phosphoric  acid,  360,  4 1  <>,  562 
Glycin,  i 

or  glycocoll.  354 
Glycocholic  acid,  359 
Glycogen,  525 

and  lactic  acid,  production  in  mus- 
cle, 745 

as  reserve  material,  531 

extra  hepatic,  530 

formation  of,  from  protein,  527.  530 

forms,  528 

function  and  fate  of,  531 

in  liver,  526 

in  muscle,  741,  742 

preparation  of,  689 
Glycogenase,  589 
Glycogenolytic  nerve  fibres,  541 
Glycolysis,  532 

pancreas  and,  537 
Glyconic  acid.  535 

Glycosuria,  after  injection  of  sugar  into 
the  blood. 690 

alimentary.  532.691 

caused  by  drugs.  543 

phlorhizin,  542,  691 

produced  by  asphyxia,  539 

puncture,  538 

relation  of  adrenalin  to.  540 
Glycuronic  acid,  47-  476.  517,  535 
Glycyl-tyrosyl-alanin,  443 
Goitre,  exophthalmic,  635 

of  brook  trout.  635 
Golgi's  method,  823 
GoU,  column  of.  838 

connections  of,  84a 
Gower,  tract  of,  838 
Gracile  funiculus.  841 
Graafian  follicles,  627 
Gracilis  experiment  of  Kiihne,  885 
Grafting  tissues.  1099 
Gramme-molecular  weight,  420 
'  Granule-cell.'  828 
Ground  bimdles  of  cord.  839 
Growth,  foods  adequate  for.  605 
Guaiconic  acid  and  oxydases,  267 
Guai.icum.  267 
Guanin.  570.  5*^- 
GUnzburg's  reagent.  454 
Gymnotus,  812 
Gyrus  postccntralis.  929 

precentralis,  929 

Ha;matochrometer.  121 
Ha}matin,  54 


iii8 


INDEX 


Haematin  acid,  75 

alkaline,  75 
Haematocrite,  27,  68 
Haematoidin,  379 
Haematopoiesis,  20 
Haematoporphyrin,  55'  7^ 

in  urine,  477 
Ha;min  55.  79 
Hremochromogen,  54,  76 
Haemoglobin,  composition  of,  50 

crystallization  of.  52 

crystals,  preparation  of,  73 

curves  of  dissociation,  251,  252 

influence  of  carbon  dioxide  on,  253 

intracorpuscular  crystallization   of, 
52 

quantitative  estimation  of,  76 

spectroscope  examination  of,  74 

spectrum  of,  51,  53 
Haemoglobinometer,  76 
Haemoglobinuria,  paroxysmal,  477 
Haemolysis.  28,71 

by  foreign  serum,  71 

mechanism  of,  29 
Hasmometer,  77 
Haemophilia,  coagulation  in,  45 
Haemorrhage  and  transfusion,  influence 
of,  on  blood-pressure,  212 
quantity  of  blood  which  may  be 
lost  in,  189 
Hair-cells  of  internal  ear,  908 
Haldane's  apparatus  for  CO2.  298 

for  H2O  and  CO2,  299 
Harmonics,  304 
Hay's  test  for  bile-salts,  520 
Head,  transplanting  of,  940 
Hearing.  1024 

analysis  of  complex  sounds,  1032 

beats,  1070 

cranial  conduct  sound,  1070 

monochord,  1070 

perception  of  pitch,  1033 

range  of,  1035 

sympathetic  vibration,  1070 

theories  of,  1034 
Heart,  action  current  of,  806, 816 

'  all  or  nothing  '  law  of,  154 

apex,  preparation  of,  192 

arrangement  of  fibres  in,  87 

auricular  flutter,  151 

automatism  of,  142 

beat,  85,  192 

cause  of,  141 

chemical  conditions  of ,  152 
neurogenic  and  myogenic  hypo- 
thesis of,  142 
standstill,  action  of  augmentor 
nerves  in,  166 

conduction  and  co-ordination  in,  146 

conductivity  of,  142 

excitability  of,  142 

extra  systoles  of,  155 


Heart,  extrinsic  nerves  of,  156 
ganglion  cells  of,  141 -163 
impulse  of,  90 
inhibitory  nerves  of,  210 
inhibition  of,  156 
intrinsic  nerves  of,  141 
muscle,  action  of  inorganic  salts  on, 

198 
nerves  of,  201 

augmentor,  157,  162 

extrinsic,  157 

in  frog,  194 

inhibitory,  157,  162 

intrinsic,  141,  157 
of  Limulus,  143 
of  mammalian.  199 
output  of,  139 
pause  of.  97 
perfusion  of.  1043 

isolated  mammalian.  203 
period  of  discharge  in.  97 

filling  of,  97 

rising  pressure  in,  97 
refractory  period  and  extra  contrac- 
tion of,  155 
resuscitation  of,  153 
rhythmicity  of,  142 
sounds  of,  88,  205 
source  of  energy  of  contraction  of, 

746 
suction  action  of,  loi 
temperature  in,  684 
tonicity  of,  142 
tracings,  192,  193, 195 

simultaneous,  from  auricle  anc 
ventricle,  193 
valves  of,  86,  202,  204 
work  done  by,  138 
Heat  centres,  675 
coagulation,  792 
distribution  of,  683 
effect  of  curara  on,  669 
equivalents  of  food  substances,  660 
given   off  in  respiration,   measure- 
ment of,  694 
in  body,  659 
in  brain,  664 
in  digestion,  687 
in  fever,  678 
in  glands,  664 
in  heart,  663 
in  muscles,  662 
in  muscular  contraction,  736 
liberated  in  cleavage  of  food  sub- 
stances, 659 
loss,  657 

voluntary  regulation  of,  667 
of  difference  classes,  662 
production,  amcmnt  of,  660 

and  work,  661 
relation  to  muscular  work,  661 
rigor.     Sec  Rigor-heat,  751 


INDEX 


1119 


Heat.  »-ats  of,  662 

Sources  of,  in  body.  659 

standstill  of  heart.  159 

surface    blood-flows,   relations    be- 
tween, 671 

voluntary  regulation  of,  667 
time,  relations  of,  738 
Heller's  test  for  albumin,  516 
Helmholtz's  phakoscope,  1059 
Hemeralopia,  1020 
Hemiana;sthesia.  capsular.  853 
Hemianopia,  894,  931 
Hemibilirubin,  359 
Hemiplegia,  reflexes  in,  883 
Hering's  theory  of  colour  vision.  1017 
Herpes  zoster  and  trophic  nerves,  779 
Hexoses,  3,  529 

Hibernating  animals,  temperature  regu- 
lation in,  677 
respiratory  quotient  in,  240 
Hiccup.  282 
Hippuric  acid,  516,  603 

formation,  571 
Hirudin  and  coagulation,  37 
Histidin,  54,  354 
Histones,  2 

Holmgren's  wools,  1069 
Homogentisinic  acid,  477.  517 
Horaoiothermal  animals,  production  of 

carbon  dioxide  in,  243 
Homo-lateral  fibres,  851 
Homologous  stimuli,  967 
Hormones,  398 

Human  milk,  composition  of,  616 
Humidity  of  air  and  heat  regulation,  666 
Hunger,  901 

sensation  of,  1054 
Hydrajmic  plethora,  495 
Hydrocele  fluid.  39 

coagulation  of.  35 
Hydrochloric  acid  in  gastric  juice,  forma- 
tion of,  373.  374 
in  starch,  410 
Hydrogen,  income  and  expenditure  of. 

607 
Hydrolysis,  2 
Hydrostomia,  394 

Hyoscyamine,  action  of.  on  pupil,  986 
Hyperglycajmia,  relation  of  adrenal  to. 

541 
Hyperisotonic  solutions,  422 
Hypermetropia,  990 
Hyperpnoea,  276 
Hypoglossal  ner\  r.  902 
Hypoisotonic  solutions,  422 
Hypophysin,  644.  647 
Hypoxanthin.  579.  582 

Identical  points,  theory  of,  997 
Tdio-muscular contraction.  7^3 
lUo-Ciecal  valve.  325 
colic  sphincter.  325 


Illusions,  optical,  tool 

Imbibition,  420 

Indican,  estimation  of.  510 

Indol-phenol.  formation  of.  in  intestine. 

417 
Indophenyloxydasc,  268 
Induction  machine,  arranged,  198 
arranged  for  single  shocks.  781 
shocks,  make  and  break,  780 
Inductorium,  703 
Infundibulum,  644.  904 
Inhibition  from  the  cortex,  921 
in  reflex  action,  875 
of  heart,  156 
nature  of.  165 
Inorganic  salts.     See  Salts 
Inosinic  acid.  741 
Inosit,  741 
Inspiration,  225 
forced.  229 
muscles  of,  225 
Intellectual  processes,  seat  of.  938 
Intelligence,  size  of  brain  and,  952 
Intermedio-lateral  tract,  836 
Internal  capsifle,  853 

frontal  fibres  in,  854 
occipito-temporal  fibres  in,  854 
respiration,  263 
secretion  of  kidney.  648 
of  ovaries,  627 
of  pancreas,  622 
of  pituitary  body.  645 
of  testicles,  626 
of  thymus,  629 
of  thyroid,  631 
Intestinal  epithelium,  permeability  of, 
431 
juice,  adaptation  of,  to  food,  409 
collection  of,  364 
composition  of,  365 
influence  of  nerves  on,  408 
segments,  effect  of  blood-serum  on 
contractions  of,  447 
action  of  epinephrin  on,  447 
Intestine,  large,  absorption  in,  445 

movements  of,  324 
Intestines,  absorption  of  water  in,  416 
contraction  of  isolated.  446 

of  segment,  324 
digestion  in.  412 
movements  of.  322 
nerves  of.  326 

reaction  of  contents  of.  413.  414 
resection  of,  445 

segment  of,  action  of  adrenalin  ia 
blood  on.  641 
Intraocular  tension.  977 
Intrathoracic  pressure.  235.  236 
Invertaso,  332,  333 

in  intestinal  juice,  365 
Inversion  of  carbo-hydrates,  350 
Iodine,  influence  of.  on  th>Toid.  635.  636 


INDEX 


Ions,  423 

Iris,  dilator  nerves  of,  21 1 

effect  of  stimulation  of  sympatfietic 
on,  983 

functions  of,  986 

in  accommodation,  983 

local  mechanism  of,  985 

nerves  of,  983 
iron,  absorption  of,  441 

in  eggs,  61C 

in  liver  cells,  457 

in  milk,  610 
Irradiation,  102 1 
Island  of  Reil,  938 
Isodynamic  relation  of  food  substances, 

747 
Isomaltose,  332 
Isotonic  and  isometric  contraction,  721 

solutions,  422 
Itching,  sensation  of,  1045 

Jacksonian  epilepsy,  937 

Japanese  dancing  mice,  labyrinth  of,  912 

Jaundice,  408 

colour  of  stools  in,  363 

haematogenic,  379 
Jaw-jerk,  887 

Karyokinesis,  5 

Karyosome.     See  Nucleolus 

Katabolic  changes  in  living  matter,  7 

Kephalin,  42,  562,  768 

Ketohexoses,  529 

Ketones,  529 

Kidney,  bloodvessels  and  tubules  of,  484 

excretion  of  pigments  by,  490 

formation  of  hippuric  acid  in,  571 

gas  exchange  of,  498 

internal  secretion  of,  648 

nerves  of,  499 

tubules  of,  485,  486 
Kinaesthetic  area.  929 
Knee-jerk,  876,  887 

reinforcement  of,  883 
Kreatin  and  kreatinin  in  protein  meta* 
bolism,  586 

in  muscle,  742 
Kreatinin,  475,  515 

excretion  and  muscular  work,  600 

in  fever,  678 

source  of,  587 
Kiihne's  artificial  eye,  1061 

Labyrinth  and  equilibration,  907 
Laccase,  268,  331 
Lachrymal  glands,  469 
Lactalbumin,  692 
Lactase,  332,  334 
Lacteals,  458 

absorption  of  fat  by,  437 
Lactic     acid     and    heat-production    in 
muscle,  741 


Lactic  acid  as  stage  in  decomposition  of 
dextrose,  535 
fermentation,  418 
formation  of,  in  muscle,  743 
Hopkins's  reaction  for,  794 
in  metabolism,  537 
in  nervous  tissue,  769 
precursor  of,  744 
Uffelmann's  test  for,  454 
Laking  of  blood,  28.     See  Hemolysis 
Landergren's  hypothesis,  542 
Langerhans,  islets  of,  624 
Lanolin,  436 
Larynx,  action  of  muscles  of,  302 

and  voice  production,  301 
Latent  period  of  muscular  contraction. 

719.  788 
Lateral  ground-bundle,  839 

nucleus  of  bulb,  845 
Law  of  contraction,  817 
Lecithin,  i,  47,  360,  562,  768 

digestion  of,  416 
Leclanche  battery,  196 
Leech  extract  and  coagulation,  38 
Left-handed  people,  936 
Legal's  test  for  acetone,  521 
Leucin,  354,  455 
Leucocytes,  chemistry  of,  55 
eosinophile,  17 
number  of,  19 
origin  of,  22 
polymorphonucleau:,  17 
transitional,  17 
varieties  of,  17 
Leucocytosis,  19 
Leukaemia,  19 

Levatores  costarum,  action  of,  in  respira- 
tion, 226 
Levulose,  529 

Lieben's  test  for  acetone,  52 1 
Lieberkiihn"s  crypts,  364,  368,  369 

functions  of,  445 
Lime  salts,  deficiency  of,  changes  caused 

by,  609 
Limulus  heart,  165 
Linolic  acid,  547 
Lipase,  48,  332 
gastric,  349 
pancreatic,  356 
reversed  action  of,  438 
Lipases  of  reversible  action,  356 
Lipoids,  I,  3 
Lipoid-solubility  of  absorbed  substances, 

431 

Liquids,  flow  of,  83 

Lissauer,  tract  of,  838 

Listing's  law,  1023 

Liver  and  coagulation,  44 
and  dccunidization,  578 
and  glycogen  formation,  526,  528 
and  metabolism  of  fat,  558 
and  urea  formation,  574 


I,\DLX 


Liver  cells,  iron  in.  457 

temperature.  6bo 
Living    matter,    chemical    composition 
of.  1 
functions  of.  6 
structure  of,  4 
Living  test-tube  expcriincnt,  34 
Lcjcalizatiou  in  difierent  animals,  945 

of  function.  940 
Locomotion,  914 
Locomotor    ataxia,     disappearance     of 

knee-jerk  in,  887 
Lungs,  area  of,  223 

auscultation  of.  298 
blood-supply  of.  222 
circulation  time  ol.  223 
mechanism  of  gas  excliange  in.  262 
quantity  of  blood  in.  223 
Lutein.  1078 

Lymph,  composition  of,  57 
dillerent  kinds  of,  460 
flow,  factors  in,  190 
formation,  and  activity  of  organs, 
446 
factors  concerned  in,  461 
influence  of  ner\  es  on.  467 
freezing-point  of,  467 
hearts,  190,  191 
post-mortem  flow  of,  468 
pressure  of,  190 
rate  of  flow  of,  190 
Lymphagogues,  462 
Lymphatic  circulation,  190 

glands,  190 
Lymphatics,  valves  of.  190 
Lymphoblasts,  22 
Lymphocytes,  17- 

Lyein.  354  .    ^    ^     ,■ 

synthesis  of.  m  body,  003 

Macula  lutea,  1064 
Magendie-Bell  law,  863 
Make  and  break  shocks.  780 
Malapteruruselectricus,  812 

nerve  of  electrical  organ,  822 
Maltase,  334 

in  intestinal  juice,  365 
Maltt)se,  absorption  of,  430 
Mammary  glands,  fat  formation  m,  550 

line.  90 
Manganese  salts  and  coagulation,  37 
Mannite.  3 
Manometer.  92 

differential.  96 
Hiirthle's  elastic.  93 
maximum  and  minimmu,  92 
optical,  93 
witli  side-tubc.  210 
Marchi  staining  reaction,  77 1 
Marginal  veil.  822.  830 
Marie,  tract  of.  839 
Mariotte's  experiment.  1004 


Mast  cells,  18 

Masi.ca.ion.  315 

Mate.  619 

Maxwell's  spot  (vision).  1065 

Meconium.  419 

Mediastinum,  225 

Medulla  oblongata,  structure  of,  841 

'  Medullary  '  grojve,  821 

sheath,  development  ol.  925 
Megakaryocytes,  18 
Megaloblasts.  21 
Meissner's  plexus.  314 
Mcniijre's  disease.  909 
Menstruation.  1076 
Mercaptmic  acid.  572 
Mesencephalon.  822 
Metabolism,  6 

in  fever,  680 

in  starvalion.  593 

iotermediary  of  carbo-hydrates.  534 
of  fat.  556 

of  amino-acids.  572 

of   nucleic  acids   and   purm  bases, 

582 
of  phosphatides.  562 
of  proteins,  503 

and  muscular  work,  599 
in  starvation,  591 
of  sterins,  56* 
relation  of,  to  surface,  670 
Meta-proteins,  3 
Metencephalon,  822 
Methxmoglobin,  53.  75 
Methylene  blue,  behaviour  of.  m  tissues, 

217 
Methylglyoxal,  537 
Methyl  orange  as  indicator,  414 
Metronome.  193 
Mett's  tubes,  337 
Microblasts.  21 
Microtometer.  257 
Micturition.  503 
centre.  504 
Milk,  1095 

as  a  food,  610 
chemistry  of,  691 
clotting  of.  692 
digestion  of.  411 
Milton's  reagent,  8 
Mitosis,  5 

Mitral  valve.  86.  96 
Moist  chamber.  782,  815 
Molecular  concentration.  420 
Molisch's  lest  for  carbo-hydrates.  11 
Monako.v's  tract,  839 
Monochord.  1070 

Monosaccharides.  absori<ti..n  of,  439 
t..rmali.-n  <>f  glycogen  from.  529 
Monro,  foramea  of,  822 
Morphine,  .luanliiy  of,  for  dogs.  03 
Morphology  of  the  blood.  14 
Motor  apliasia,  935 

7» 


INDEX 


"  Motor  "  areas,  918 
Mountain  sickness,  292 
Movements,  forced,  912 
Mucin  in  bile,  358 

in  saliva,  448 
Mucous  glands,  secretory  changes  in,  375 
MUller's  experiment,  290 
Muscarine,  action  of,  on  heart,  164,  197 
Muscle,  action  of  curara  on,  784,  712 

action  of  nicotine  on,  713 

anaerobic  contraction  of,  744 

arrangement  for  tracings,  785 

chemistry  of,  792 

composition  of,  741 

contraction,  influence  of  load  on,  72 1 

degeneration  of,  jyj 

diffraction  spectrum,  719 

direct  excitability  of,  712,784 

direct  stimulation  of,  714 

efficiency  of,  739 

elasticity  of,  709 

extensibility  of,  709 

fatigue  of,  723 
cause  of,  725 
seats  of,  727 

formation  of  lactic  acid  in,  743 

gases  of,  266 

general  physiology  of,  696 

heat -production  in,  662 

"  idio-muscular "    contraction     of, 

733 
nerve  preparation,  781 

fatigue  of,  786 
of  eyes,  extrinsic,  1023 
oxygen  consumption  of,  267 
permeability  of,  747 
physical  properties  of,  709 
reaction  of,  743,  793 
receptive  substances  of,  713 
respiratipn  of,  265 
smooth,  contraction   of,    719,   721, 
790 
wave  of  contraction  in,  733 
spindles,  777 
stimulation,  711 
structure  of,  716 
trough, 782 
Muscular  contraction  and  lactic  acid,  741 
changes  during,  718 
chemical  phenomena  of,  741 
CO2  production  in,  742 
duration  of,  719 
graphic  record  of,  784 
heat -production  in,  736,  737 
in  absence  of  oxygen,  300 
influence  of  fatigue,  786 
of  load  on,  786 
of  mental  fatigue  on,  728 
of  previous  stimulation  on, 

723 
of    tpmi)erature    on,    723, 
786 


Muscular  contraction,  influence  of  vera 

trine  on,  728,  887 
isotonic  and  isometric,  721 
latent  period  of,  719,  788 
mechanical  phenomena  of,  719 
O2  composition  in,  742 
optical  phenomena  of,  716 
physico-chemical  conditions  of, 

747 
rate  of  wave  of,  733 
relation    between    mechanical 

energy  and  heat -production. 

739 

relation  of  glycogen  to,  745 

substances  metabolized  in,  745 

superposition  of,  730 

theories  of,  718 

time  relations  of,  721 

voluntary,  734 

work  done  in,  721 
sensations,  1052 
tissue,  action  of  extracts  of,  650 
tone,  889 
work  and  nitrogmous  metabolism, 

599 
source  of  energy  of,  600 
Musical  centres,  933 
Myelencephalon,  822 
Myelin  sheath,  fragmentation  of,  77c 
Myelination  of  tracts  at  different  times, 

927 
Myeloblasts,  22 
Myograph,  192,  719 
spring,  720,788 
Myohasmatin,  741 
Myosin,  793 
Myosinogen,793 
Myxcedema,  633 

Negative  variation.    See  Action  current 
Nerve,  carbon   dioxide    production    in. 
756 
chemical  changes  in,  756 
chemistry  of,  768 
conductivity  of,  764 

anaesthetics  and,  787 
degeneration  of,  769 

phosphorus  in,  771 
endings,  action  of  drugs  on,  180 
excitability  of,  758 

and  conductivity  of,  760 
fibres,  meduUatcd,  832 
structures  of,  823 
heat -production  in,  756 
impulse,  nature  of,  755 
velocity  of,  767,  791 

temperature  coefficient  of, 
756 
muscle  preparation,  781 
pattern  of,  773 
polarization  of,  802 
propagated  disturbance  of,  755 


INDEX 


1123 


Nerve,  re^eaeration  <jf,  772 
autogenetic,  776 
chemiotaxis  in,  774 
stimulation  of.  757 
trunks,  ccxjliiig  of,  945 
Nerves,  anastomosis  ni.  772,  940 
cUssirication  of.  780 
posterior  roots  of.  930 
preganglionic,  837 
specific  energy  of.  943 
trophic.  778 
Nerve-cells,  bipolar,  grt)«  th  in  vitro,  828 
efiect  of  an.-Emia  on,  831 
ana-sthetics  on,  831 
divisions  of  axons  on,  831 
fatigue  on,  831 
growth  of,  in  vitro,  776 
of  Golgis,  second  type,  828 
Nervi  erigentes,  177 
Nervous  sysem,  autonomic,  963 

development    of,    in    different 
animals,  870 
tissue,  action  of  extracts  of.  650 
Nervus  erigens.  326.  328 
Neural  canal,  821 

groove.  821 
Neuroblasts,  821.  830 
Neuroglia,  833 
Neurokeratin,  769 
Neurons,  823 

growth  of.  829 
nutrition  of.  S30 
scheme  of  lower  motor,  827 
varieties  of,  827 
Nicotine,  action  of,  on  ganglion  cells  of 
heart,  164 
on  skeletal  muscle,  713 
on  sympathetic.  i8o,  965 
effect  of,  on  nerve-cells.  180 
Night-blindness,  1020 
Nitrogen  balance-sheet.  591 

necessary  quantity  of.  in  diet.  613 

total  estimation  of.  514 

variation  of.  with  protein  in  food, 

693 

Nitrogenous  equilibrium,  591 

protein  necessary  for.  594 

metabolism  and  muscular  work,  599 
Nissl  substance,  948 
Nissl's  bodies.  823 

method.  823 
Norleucin.  354 
Normal  solution,  473 
Normoblasts,  21 
Nuclease,  583 
Nucleic  acids,  chemistry  of,  582 

metabolism  of,  582 
Nucleo-proteins,  i,  2,  47 

digestion  of,  411,  582 
Nucleosides,  svnthesis  of,  586 
Nucleotidase,  583 
Nucleotids,  582 


Nucleus,  5 

globosus,  857 

importance  of,  for  cell,  769 

tecti,  857,  899 

Oatmeal  as  a  food,  614 
Obesity,  559 

Banting  cure  for,  595 
treatment  of.  561 
Occipital  lesions,  932 
Oeulo-motor  nerve,  895 
Odours,  classification  of.  1036 
CEsophagus,  c<mtractions  of.  790 

pulse.  99 
Ohm's  law.  698 
Oleic  acid.  547 
Olcin,  4 

Olfactometer,  1037 
Olfactory  bulb,  893 

nerve,  892 
Olivo-spinal  tract.  R39,  857 
Oncometer,  500 
Oophorin,  628 
Ophthalmomctei.  1062 
Ophthalmoscofc.  1065 

Geneva,  1067 
Opsonins,  61 
Optical  illusions.  looi 
0|)tic  lobes,  003 

and  iiifiibition  of  reflexes.  882 
nerve,  893 

radiation,  855,  894 
thalamus.  855 
thalmi.  903 
Orcin  reaction  for  pentoses,  520 
Orientation,  mechanism  of.  907 
Ornithin.  602 
Osmosis.  420 

and  diffusion,  lymph  formation  in, 
465 
Osmotic  pressure,  420 

resistance  of  coloured  corpuscles,  73 
Ossicles,  auditory,  1029 
Otoliths,  908 
Output  of  heart,  139 
Ovaries,  internal  secretion  of,  627 
Ovary,  influence  on  metabolism,  628 
Overtones,  304,  307 
Ovum,  development  of  the,  1078 
Oxalates,  action  of.  on  coagulation,  37.  64 

in  urinary  sediments,  475 
Oxidation,  seats  of.  263 
Oxidative  process,  nature  of,  267 
Oxidizing  ferments  or  o.\ydases.  267 
Oxvbutyric  acid.  546 
Oxydases.  48.  76,  300 
Oxygen  absorption,  mechanism  ot,  262 
carrying  capacity  of  blood,    uliliia- 

tion  of.  672 
consniM|>ti(Mi  of.  241.  m 

in  different  animals,  141 
of  different  tissues,  267 


1 1  24 


INDEX 


Oxygen  deficit,  608 

discribution  of,  in  blood,  250 
income  and  expenditure  of,  607 
partial  pressure  of,  in  aheoli,  261 
tension  in  blood,  carLon  monoxide 
method,  258 

Oxyntic  cells,  369 

Oxyprolin,  354 

Pain,  1073 

in  internal  organs,  873 
referred,  863 
sensations,  1043 
paths  for,  868 
Pancreas  and  spleen,  mutual  relations 
of,  405 
influence  of  nerves  on,  399,  401 
internal  secretion,  622 
islei  tissue  of,  624 
removal  of,  in  pregnancy,  624 
Pancreatic  juice,  adaptation  of,  to  lac- 
tose, 404 
and   bile,  adjuvant   action  of, 

361 
artificial,  454 
composition  of,  352 
ferments  of,  454 
freezing-point  of,  380 
rate  of  secretion  of,  404 
secretion,    influence    of    food    on, 
403 
Panniculus  adiposus,  559 
Parabiosis,  623,  iioi 
Paradoxical  contraction,  805,  816 
Paraglobulin,  48 
'  Paralvtic  '  secretion  of  intestinal  juice, 

408  ' 
Paraphasia,  937 
Parasternal  line,  90 
Parathyroid,  effects  of  removal  of,  632 

location  of,  631 
Parenteral  absorption  of  proteins,  33 
Parotid,  secretory  changes  in.  369 
Paroxysmal  tachycardia,  electro-cardio- 
gram, 809 
Parthenogenesis,  1076 
Partial  pressure  of  gases,  246 
Parturition,  1093 

Peduncle,  inferior,  of  cerebellum,  857 
Pellagra,  619 
Pelvic  nerves,  177,  326 
Pendulum  movements  of  intestines,  322 
Pengavar  Djambi,  962 
Pentoses,  520 
Pentosuria,  482 
Peptases.  355 
Peptides,  2 
Peptones  and  coagulation,  37 

tests  for,  10 
f'ercussion,  231 
Perfusion  of  heart,  203 
Perikaryon,  822 


Perimetry,  1018 

Periodic  breathing,  production  of,  294 

Peripheral  reflex  centres,  884 

Peristalsis,  318,  323 

Peritoneal     cavity,     absorption    from, 

433 
Peroxydase,  76 

Persistence  theofy  (vision),  1010 
Perspiration,  visible  and  invisible,  505 
Pettenkoler's  test  for  bile  acids,  360 
Phagocytosis,  59 
Phakoscope,  Helmholtz's,  1059 
Phenol,  excretion  in  starvatu.n,  593 
Phenolphthalein  as  indicator,  413 
Phenyl-alanin,  2,  346,  354 
Phenyl-hydrazme  test  for  sugar,  517 
Pho-carnic  acid,  741 
Phosphates,  estimation  of,  509 
Phosphate  triple  sediments,  523 
Phosphatides,  76S 

digestion  of.  415 

metabolism  of,  562 

synthesis  of,  586 
in  body,  596 
■    Phospho-proteins,  2 
I    Phosphorus  in  degenerated  nerve,  771 

in  milk,  610 

poisoning  and  fat  migration,  554 
Photo-electric  reaction  of  eye,  811 
Phlebogram.  loi 
P  ilorhizin  glycosuria,  542.  691 
I'hloroglucin  reaction  for  ]  eiitoses,  520 
Phrenic,  nerves  and  respiration,  269 
Phytosterins,  360,  561 
Pia  mater,  833 
Pilocarpine,  180 

action  of,  on  nerve -endings,  180 

effect  of,  on  heart.  197 
I    Pilo-motor  nerves,  885 
Pineal  body,  904 

gland,  648 
Piotrowski's  tests,  8 
Pitch,  304 
Pithing  a  frog,  191 
Pilot's  tubes,  121 
Pituitary  body,  644,  904 

action  of  extracts  of,  647 
functions  of,  64S 
removal  of,  645 
Piston  recorder,  232 
Placenta,  exchange  of  materials  in.  1085 
Plane  of  traction,  1023 
Plantar  reflex,  887 
Plasma,  proteins  of,  49 
Plasmine  of  1  )enis,  34 
Plasn^olysis,  422 
Platelets  and  coagulation,  37 
Plethysmograph,  128 
Plethysmographic  tracings.  208 
Pleural  cannula,  233 

Poikilothermal    animals,    production    of 
carbon  dioxide  in,  243 


INDEX 


1125 


Poiseuille,  85 

Poiseuille's  laws  of  flow,  85 

Polar  stimulation,  law  of,  715 

Polarimeter,  519 

Polarization  of  muscle  and  nerve,  803 

Polygraph,  103 

tracings,  207 
Polymorphonuclear  leucocytes,  17 
Polypeptides,  2,  355 
Pol>-saccharides,  3 
^ons,  903 

connections  of,  855 

grey  matter  of.  855 
Post -central  gyrus,  929 
Posterior  longitudinal  bundle,  857 
Posterior  root  ganglia,  development  of, 

822 
Post-sphygmic  interval  of  heart,  97 
Potassium  in  muscle,  741 

salts,  influence  of,  on  heart-beat,  153 
Potential  electrical,  697 
Precentral  gyrus,  929 
Precipitins,  31 
Prepyramidal  tract,  839 
Presphygmic  interval  of  heart,  97 
Pressor  nerves,  171 
Pressure,  1041,  1071 

blood-,  measurement  of  arterial,  109 
influence  of  excision,  115 
Primary  colours,  1013 
Prisms,  970 
Proferment,  337 
Prolamins,  604. 
Prolin,  346,  354-  603 
Propionic  acid,  547 

transformation   into   dextrose, 
530 
Proprio-ceptive  fields,  886 

spinal  fibres,  840 
Pro-secretin,  402 
Protamins,  2 

and  coagulation,  44 
Proteins,  i 

absorption  of,  441 

'  building  stones  '  of,  567 

cleavage  of,  and  absorption,  442 
products  of,  354 

colour  reactions  of,  8 

complete  and  incomplete,  602 

consumption  determined  by  supply, 
596 

digestion  of,  411 

formaldehyde  reaction,  8 

formation  of  glycoj^en  from,  530 

general  reactions  of,  7 

Heller's  test  for,  516 

in  nutrition,  relative  value  of  dif- 
ferent, 601 

living  and  dead,  566 

metabolism  of.  563 

necessary  amount  of,  6n,  612 

of  tissues,  specificity  of,  566 


Proteins,  parenteral  absorption  of,  33 

precipitation,  reactions  of.  8 

specificity  of,  315 

synthesis  of,  564 

temperature  of  coagulation,  9 
Protein-sparing  action  of  fat.  595 

01  carbo-hydrates.  595 
Proteoses.  3 

action  of.  on  blood-pressure,  171 
on  coagulation.  37,  63 
on  clotting,  44 

(and  peptones),  influence  on  blood- 
pressure.  213 

formed  in  gastric  digestion.  346 

secij!iiiar\',  13 

tests  for,  10 
Prothrombin,  36 
Protoplasm,  structure  of,  4 
Prozymogen,  397 

granules,  371 
Pseudo-globulin,  49 

-portia,  17 

reflexes,  876 
Ptyalin,  410 
'  Puberty  gland,'  627 
Pulmonary  catheter,  257 
Pulse,  anacrotic,  106 

arterial,  loi 

curve,  variation  in  form  of,  106 

effect  of  arayl-nitrate,  207 
exercise  on,  207 

frequency  of,  107 

rate,  208 

tracings,  103 

venous,  loi,  131 

wave,  rate  of  propagation  of,  108 
Pulsus  alternans,  155 

bigeminus,  155 
Pulvinar,  904 
'  Puncture  '  fever,  676 

glycosuric,  538 
Pupillo-dilator,  211 

fibres,  1067 
Purin  bases  in  urhie,  475 

metabolism  of,  582 

bodies,  chemistry  of,  583 
Purins,  excretion  of,  584 
Purkinje  fibres  of  heart.  147 
Purkinje's  figures,  1002.  1070 
Putrefaction  in  intestine,  417 

of  proteins,  action  of  products  oi, 
649 
Pyloric  sphincter,  relaxation  of,  321 .  4it 
Pyramidal  cells,  825 

nerve -cells,  development  of.  %2% 

path  in  intcnial  capsule,  850 

tracts.  838 

connections  of.  847 
in  different  animals.  849 
Pyramidin  bafici.  582,  584 
Pyramids,  decussation  of.  S50 
Pyruvic  acid.  536,  537 


II26 


l.\DEX 


Quadratus    lumborum,    action    of,    in 
respiration,  226 

Radiation  from  the  skir,  657 
Radiometer,  657 
Raffinose,  334 

Rarefied  air,  eflects  of  breathing,  291 
Rations,  soldiers',  615 
Reaction  of  degeneration,  777 
of  intestinal  contents,  413 
'  Receptive  '  substances,  180,  713 
Receptor  in  reflex  action,  r61e  of,  87a 
Receptors,  870 

Reciprocal  relation  of  vasomotors,  184 
Recurrent  sensibility,  864 
Referred  pain,  863 

Reflex  action,  anatomical  basis  of.  870 
flexion,  960 
inhibition  in,  875 
irradiation  of,  877 
of  spinal  cord,  869 
scratch,  960 
arc,  fatigue  of,  874 

isolated  conduction  of  impulses 

in,  871 
peculiarities  of  conduction  in, 

874 
properties  of,  874 
refractory  state  in,  875 
cardiac  death,  169 
centres  in  cord,  887 
peripheral,  884 
inhibition,  168 
of  heart,  208 

through  pulmonary  nerves,  168 
time,  886 
Reflexes,  axon,  776,  885 
common  path  of,  871 
co-ordination  of,  880 
effect  of  strychnine  on,  871 

tetanus  toxin  on,  871 
facilitation  of,  881 
in  disease,  886 

influence  of  brain  on  spinal,  882 
in  hemiplegia,  883 
inhibition  of  antagonistic,  88a 
in  man,  961 
long  spinal.  879 
reversal  of,  875 
r6le  of  the  receptor  in,  873 
short  spinal,  878 

simultaneous,  combination  of,  880 
successive    combinations    of,    880, 

881 
superficial,  886 
vaso-motor,  183 
Refractory  period  of  heart,  155 
Regeneration,  autogenetic,  776 
of  nerves,  772 

after  anastomosis,  77a 
bifurcation  of,  776 
of  tissues,  1074 


Regulation  respiration,  276 
Reil,  island  of,  938 
Renal  calculus,  pain  caused  by,  873 
Rennin,  347,  692 

function  of,  348 
Reproduction,  1074 

in  higher  animals,  1075 
Reserve  air,  235 
Resistance,  electrical,  697 
measinrement  of,  698 
Resonance,  231,  304,  308 
Respiration,   accessory   phenomena  of. 
230 
afferent  nerves  of,  270 
and  blood-pressure.  253 
and  nervous  system,  268 
artificial,  200,  229 

influence  of,  on  blood-pressure. 
286 
breaking-point  in,  233 
by  insufflation  of  oxygen,  202 
calorimeter,  239 
chemical  regulation  of,  275 
chemistry  of,  238 
comparative,  221 
cutaneous,  292 
efferent  nerves  of,  269 
external,  221 
forced,  influence  on  carbon  dioxidt 

excretion,  244 
frequency  of,  233 
heat  given  off  in,  694 
in  condensed  and  rarefied  air,  289 
influence  of  cutaneous  nerves  on,  274 
of  muscular  exercise  on,  274 
of  superior  laryngeal  nerve  on, 

272 
of  vagi  on, 270 
internal,  221,  263 
mechanical  phenomena  of,  224 
methods  in  chemistry  of,  238 
of  muscle,  265 
types  of,  228 
Respiratory     apparatus,     physiological 
anatomy  of,  222 
capacity,  235 
centre,  268 

action  of  carbon  dioxide  on,  275 
of  deficiency  of  oxygen 
on,  275 

automaticity  of,  278 
spiral,  279 
'  dead  space,'  235 
exchange,  241 

gravimetric  method,  239 
Zuntz's  method,  239 
movements  in  animals,  tracings  ol* 
294 
in  man,  293 
recording  of,  232 
pressure,  298 

variations  of,  237 


INDEX 


127 


Respiratory  quotient.  240 
sounds,  230 
tracings,  232 
Restiform  body,  857,  864 
Resuscitation  of  heart,  153 

scratch  reflex  in,  880 
Reticular  formation,  837,  842 
Retina,  development  of.  822 

epithelium,  pigmented,  1008 
experiment.  1059 
fatigue  of,  1068 

sensibility  of  different  parts,  1018 
time  needed  for  excitation,  1009 
Retinoscope,  Geneva,  1067 
Retinoscopy,  1066 
Reverser,  706 
Rheocord,  701,783 
Rhinencephalon,  ^93,  934 
Rhodopsin,  1006 
Ribose,  582 

Right-handed  people.  936 
Rigor,  carbon  dioxide  given  of!  in.  266 
heat-production  of  carbon  dioxide 

in.  751 
mortis.  748.793 

and  muscular  contraction,  750 
production    of   carbon   dioxide 
in,  751 
of  lactic  acid  in,  750 
removability  of.  753 
time  of  onset  of,  750 
production  of  heat  in,  753 
Ringer's  solution,  66 
Ritter's  tetanus,  804, 818 
Ritter-Valli  law,  759 
Riva-Rocci  apparatus.  113 

for  blood-pressure,  211 
Rolandic  area  of  cortex.  919 

sensory  function  of,  929 
fissure.  847 
Rolando,  fissure  of.  Thane's  rule,  923 

finding  position.  929 
Rontgen  rays  for  study  of  gastro-intes- 

final  movements.  322 
Rouleaux  formation.  16 
Rubro-spmal  tract,  839 

connections  of.  856 

Saliva,  action  of.  in  stomach,  342 

amylolytic  action  of.  341,  449 

antilytic  secretion  of.  392 

chemistry  of,  3^8,448 

effect  of  drugs  on  secretion  of.  451 

freezing-point  of,  381 

functions,  340 

paralytic  secretion  of.  391 

psvchical  secretion  of,  393 

reflex  secretion  of,  392 
Salivary  centre,  394 

glands,  cranial  nerves  of.  386. 450 
extirpation  of.  650 
svmpathrtic  nerves  of.  388.  451 


Salivary  glands,  trophic,  secretory  fibres 

of,  309 
Salt  hunger,  375,  609 

solution,  physiological.  192 
Salts,  absorption  of.  440 
in  diet,  617 

in  food,  r61e  of,  in  nutrition ,  608 
Saponification,  u,  361 
Sajjonin,  laking  of  blood  by, 70 
Sarkin,  579 

Scalene  muscles  in  respiration,  226 
Scheiner's  experiment  (vision),  ic6o 
Schlitz's  law  of  ferment  action,  336 
Sclero-proteins,  2 
Scratch  reflex,  873 

in  resuscitation,  880 
Scurvy.  619 

Sealing  of  wounded  vessels,  46 
Sebaceous  glands,  fat  formation  in.  556 

sebum.  505 
Secondary  contraction,  201 ,  814 
Secretin.  401 
Secretion,  internal,  621 
of  eye-liquids,  976 
Secretory  changes  in  pancreas,  369 

pressure  of  urine.  499 
Segmentation  of  food  in  intestine,  323 
Semicircular  canals  and  equilibration.  907 
Semilunar  valves.  89 

and  dicrotic  wave,  105 
moment  of  closure  of,  96 
Semisection  of  cord,  effects  of,  866 
Sensation,  reaction  of  stimulus  to,  1057 
Sensations,  cold,  1041 
cutaneous.  1038 
heat.  1041 
hunger.  1054 
muscular,  1052 
ordinary,  934 
tactile,  934 
thirst,  1054 
touch,  1038 
Sensibility,  recurrent.  864 
Sensori-motor  area,  929 
Sensor}-  aphasia,  935,  937 
areas,  visual  centres.  931 
functions  of  Rolandic  area,  929 
paths,  decussation  of.  866 
in  internal  capsule.  853 
scheme  of,  852 
Septo-margiual  bundle,  840 
Serin.  354 

Serratus  posticus,  action  of,  in  respira- 
tion, 226 
Serum,  action  of.  on  artery  rings,  66 
albumin.  47.65,  793 
coagulation  of.  47 
composition  of.  47,65 
globulin,  34- 47-65 
immune.  31 
inorganic  salts  of,  40 
proteins  65 


II28 


INDEX 


Sexual  organs,  internal  secretion  of,  626 
Sham  feeding,  396 
Shock,  anaphylactic,  32 
spinal,  860,  884 
surgical,  190 
Sighing,  282 
Sino-auricular  node,  81 
Sinus  venosus,  stimulation  of,  196 
Skate,  electrical  organ,  814 
Skatol,  419 

formation  of,  in  intestine,  417 
Skatoxyl  in  urine,  511 
Skiascopy,  994, 1066 
Skin,  action  currents  of,  810 

effects  of  varnishing,  2§2,  673 
excretion  by,  504 
respiration  by,  292 
Smell,  1035, 1071 

centre  for,  933 
Smooth  muscle,  composition  of,  942 
Snake-venom,  efiect  of,  on  coagulation, 

43 
Sneezing,  282 
Solutions,  13 

scheme  for  testing,  13 
Sorbite,  3 

Specific  energy  of  nerves,  943 
Speech,  306 

nervous  mechanism  of,  309 
Spermin,  628 
Sphincter  ani,  314 
cardiac,  314 
pylori,  314 
Sphygmograph,  Marey's,  103 

Dudgeon's,  206 
Sphygmograph ic  tracings,  206 
Sphygmomanometer  of  Erlanger,  114 

of  Hill  and  Barnard,  115 
Spinal  accessory  nerve,  902 

united  with  facial,  940 
cord  and  bulb,  centres  of,  890 
automatism  of,  888 
conduction    of     nervous     im- 
pulses by,  862 
consciousness  in,  861 
effects  of  transection  of,  860 
grey  matter  of,  835 
reflex  action  of,  86g 
scheme  of  cross-section  of,  839 
section  of,  to  show  tracts,  837 
semisection  of,  effects  of,  866 
ganglia  and  reflexes,  884 
cells  of,  826 
development  of,  822 
fatigue  of,  885 
roots,  degeneration  of,  771 

function  of,  863 
shock,  884 
Spinotectal  fibres,  846 
Spino-thalamic  fibres,  846 
Spirograph  of  Fitz,  293 
Spirometer,  234 


Splanchnic   nerve   and  hyperglyr£emia» 

541 
Spleen  and  pancreas,  mutual  relations 
of,  405 
functions  of,  650 
proteolytic  enzyme  of,  405 
Spongioblasts,  821 
Staircase  phenomenon,  156,  725 
Standing,  913 

Stannius'  experiment,  144,  192,  197 
Starch,  tests  for,  11 
Starvation,  excretion  of  urea  in,  593 
loss  of  weight  of  organs  in  excretioa 

of  urea  in,  592 
metabolism  in,  593 
protein,  metabolism  in,  591 
Stasis,  191 
Steapsin,  352,  357 
Stearic  acid,  547 
Stercobilin,  418 
Stereognosis,  929 
Stereoscopic  vision,  999 
Sterins,  360 

digestion  of,  416 
metabolism  of,  561 
Stilling,  cervical  and  sacral  nuclei  of, 

836 
Stimulants,  617 

Stimulation  by  voltaic  current,  715, 783 
chemical,  757 
law  of  Polar,  715 

recording  beginning  and  end  of,  199 
Stimuli,  adequate,  873 
different  kinds  of,  711 
summation  of,  730,  789 
Stimulus,  relation  of,  to  sensation,  1057 

Weber's  law,  1057 
Stomach,  absorption  of  proteins  by,  412 
auto-digestion  of,  459 
digestion  of  fat  in,  415 
excision  of,  351 
.     movements  of,  320 
nerves  of,  325 
pouch,  396 

protection  from  gastric  juice.  382 
Stokes-Adams  disease,  150 
Striffi  acusticffi,  899 
Striped  muscle,  structure  of,  717 
Strcmuhr.  120 
Strychnine  and  reversal  of  reflexes,  876 

efiect  of,  on  reflexes,  871 
Subcortical  sensory  aphasia,  937 
Substantia  nigra,  842 
Substrate,  333 
Succus  entericus,   364.    See  Intestinal 

juice 
Suckling,  food  requirement  of,  616 
Sugar  and  muscular  work,  533 
constitution  of.  529 
consuimption  of,  in  diabetes,  545 
destruction  of,  533 
formation  of,  from  amino-acids,  530 


INDEX 


1129 


Sugar,  formation  of,  from  fatty  acids.  530 

in  blood.  525 

intermediary  metabolism  of,  534 

in  urine,  tests  for,  517 

regulating  centre,  539 
mechanism,  538 
Sulphates,  estimation  of,  510 
Sulphocyanide  in  saliva,  448 
Summation  of  stimuli,  789 
Superposition  of  contractions,  730.  789 
Supi>leiuental  air,  235,  297 
Suprarenal  capsules  and  coagulation,  45 

extract,  effect  of,  on  blood-pressure, 
214 
Suprarenals,  638.     See  Adrenals 
Suprarenin.    See  Adrenalin 
Surface  and  mass  of  body,  relation  be- 
tween, 670 

heat -production  and  blood-flow,  re- 
lations of,  671 

phenomena  and  absorption,  425 

tension,  423 

and  muscular  contraction,  718 
Surgical  shock,  190 
Suturing  bloodvessels,  iioo 
Sweat-centre,  506 

composition  of,  504 

function  of,  507 

quantity  of,  505 

secretion  of,  influence  of  nerves  on, 
506 
Swim -bladder,  secretion  of  gases  in,  262 
Sympathetic,  action  of  nicotine  on,  180 

cardiac  fibres  of,  in  frog.  194. 197 

cervical,  vaso-motor  fibres  in,  215 

ganglion  cells,  action  of  nicotine  on, 
180 

nervous  system.  963 

vibration.  1070 
Synapse,  824 

resistance  of.  871 
Syntheses  in  the  body,  534 
Systoles,  extra,  155 

Tachycardia,  901 

Tactile  sensations,  934,  1039 

paths  for.  868 
Talbot's  law,  1070 

(vision),  loio 
Tambour,  91 

for  respiratory  movements,  232 

Marey's.  206 
Taste.  1036,  1070 

centre  for,  934 

nerves  of,  896 
Taurin,  359.  570 
Taurocliolic  acid.  359 
Tea.  619 
Tears.  469 
Teeth.  316 
Tegmentum.  842 
Telencephalon.  822 


Telodendrion,  824 
Temperature,  651 

dai  .  curve  of.  6S7 

discrmiination,  1073 

in  cavities  of  heart.  684 

in  mouth,  686 

in  rectum.  686 

normal  variations  in.  686 

of  blood.  684 

of  body. 656 

measurement  of.  652 

of  brain.  686 

of  coagulation.  9 

of  different  parts.  685 

of  skin,  686 

post-mortem  rise  of,  688 

regulation,  influence  of  ciirara  on. 
668 
in  hibernating  animals,  677 

sensations.  1072 
paths  for.  868 

topography,  683 
Tension  of  carbon  dioxide  in  blood,  260 

of  gases,  247 

surface.    See  Surface  tension 
Testes,  interstitial  cells  of,  627 
Testicle,  action  of  extracts  on,  628 
Testicles,  internal  secretion  of,  626 
Tetanizing    current,    arrangement    for, 

198 
Tetanus,  composition  of,  789 

electrical.  730 

Hitter's.  818 

secondary.  805 

toxin  elTect  of.  on  reflexes,  871 
Tetany,  after  parathyroidectomy,  632 
Thalamico-spinal  tract,  839,  857 
Thane's  method   for  Ending  fissure  of 

Rolando,  929 
Theine,  619 
Theory,  Hering's,  of  colour  vision,  1017 

of  identical  points,  997 

Young-Helmholtz.  1013 
Thermo-electric  junction,  652,  656 
Thermogenic  nerves,  780 
Thermometer,  electrical  resistance,  756 

maximum,  632 

resistance.  652 
Thermometry,  651 
Thermopile,  737 
Thermotaxis,  665 
Theosulphuric  acid  in,  478 
Thirst,  901 

sensation  of,  1057 
Thiry's  fistula,  364 
Thrombin,  35 

formation  of,  36 

nature  of  action  on  fibrinogen,  41 

preparatifin  of,  41 

specificity  of,  40 
Thrombocytes.    See  Blood  plate* 
Thrombogen,  36 


II30 


INDEX 


Thrombogen,  sources  of,  38 

specificity  of,  40 
Thrombokinase,  36 

preparation  of,  65 

sources  of,  38,  40 

specificity  of,  40 
Thromboplastic  substances,  41 
Thrombo-regulative  mechanism,  43 
Thrombosis,  45 
Thrombotaxis,  42 
Thumb  centre,  938 
Thymin,  582 
Thymus,  involution  of,  630 

lymphocytes  of,  629 

relation  of,  to  sexual  glands,  630 

removal  of,  629 
Thyroid  and  heat-production,  673 

changes  with  meat  diet,  635 

influence  of  iodine  on,  636 

of  nutritive  conditions  on,  634 

iodine  in,  635 

nerves  of,  637 
Thyroidin,  637 

Thyroids,  effects  of  excision  of,  631,  633 
Tickling,  sensation  of,  1045 
Tidal  air,  234 

measurement  of,  297 
Timbre  of  sounds,  304 

of  vowels,  307 
Time-markers,  193,  706 
Tissue  extracts  and  coagulation,  36 

respiration,  263 
Tissues,  cultivation  of,  outside  the  body, 
1097 

transplantation  of,  1098 
Tone  of  muscles,  889 

vaso-motor,  182 
Tonsils,  314 
Topognosis,  929 
Torpedo,  813 
Torricelli's  theorem,  83 
Touch,  1038,  1071 

aesthesiometer,  1040 

areas,  warm  and  cold,  1042 

pressure  sensations,  1040 

sensations  of  cold  and  heat,  1039 

•spots,  1040 
Trachea,  to  put  a  cannula  in,  200 
Tracheal  cannula,  199 
Tracts  in  spinal  cord,  837 

myelination  of,  927 
Transfusion,  influence  on  blood -pressure, 

212 
Transplantation  of  tissues,  1098 
Traube-Hering  curves,  287 
Tricuspid  valve,  86,  96 
Trigeminus  nerve,  895 
Tripalmitin,  547 
Tristearin,  i,  547 
Trochlear  nerve,  895 
Trommer's  test,  10 

for  sugar,  517 


Trophic  nerves,  778 

tone,  889 
Trypsin,  352,  353 
Trypsinogen,  352 
Tryptophane,  2,  354 
Tuning-fork,  785 
'Twitch,'  719,784 
Tympanimi,  1025 
Tyrosin,  2,  354.  455 

Momer's  test  for,  456 
Tyrosinase,  268 

UifelmJinn's  test  for  lactic  acid.  454 
Ultra-microscope,    coagulation    studiec 

by.  39 
Uncinate  gyrus,  934 
Uracil,  582 
Urea,  47 

estimation  of,  511,512 
excretion  of,  in  starvation,  593 

premortal   rise    in    starvation 

592 

formation  of,  572 

process  of  formation  of,  577 

reaction  of,  511 

secretion  in  fever,  68 1 
Uric  acid,  474.  515 

destruction  o  ,  5S5 

exogeneous  and  endogenous,  585 

formation  of,  575,  579,  580 

in  gout,  579 

sources  of,  581 
Uricolysis,  585 
Uricoxydase,  585 
Urine,  acidity  of,  472,  473,  508 

albiunose  in, 517 

amino-acids  in,  475,  483 

ammonia  in,  474.  513 

bile-pigments  in,  483 

carbo-hydrates  in,  476 

chlorides  in.  508 

chlorine  in,  477 

composition  of,  470 

cystin  in,  482 

estimation  of  sugar  in.  518 

ethereal  sulphates  in,  478 

expulsion  of,  503 

ferments  in,  477 

freezing-point  of,  479.  5^1 

hajmatoporphyrin  in,  477 

hippuric  acid  in.  475, 5^6 

in  disease,  480 

in  fever,  677 

incontinence  of,  504 

indican  in,  510 

indoxyl  in,  478,  482 

kreatinin  in,  475,  515 

oxalic  acid  in,  475 

phenol  in,  478 

phosphates  in,  509 

phosphoric  acid  in,  477 

physicfchemical  analysis  of,  479 


INDEX 


1131 


Urine.  1  iginents  of,  476 
puiieiiis  in,  483.  516 
pur.n  bases  in,  475 
real  sj.-ptionof.from  thetubules,489 
secretiuii  of,  484 

Heidenbain's  experiments  on, 

490 
influence  of  circulation  on,  499 

of  nerves  on, 301 
Nussbaum's    experiments    on» 

492 
pigments,  by  the  kidney,  490 
theories  of,  487 
work  done  by  kidney  in,  497 
secretory  pressure  of,  in  the  kidney. 

499 
sediments  of,  523 
skatoxyl  in,  511 
specific  gravity  of,  508 
sugar  in,  482,  4^3.517 
sulphates  in,  510 
sulphuric  acid  in,  478 
systematic  examination  of.  523 
temperature  of,  686 
total  nitrogen  in,  514 
urates  in,  523 
urea  in,  474,  481,  511 
uric  acid  in,  474,  481,  515,  523 
Urobilin,  359,  418,  476 
Urobilinogen,  359 
Urochronie,  476 
Uroerythrin,  476 
'  Urohypertcnsine,'  649 
Urorosein,  476 
Uterine  rings,  isolated,  IIOI 
Utricle,  907 

Vago-s>-nipathetic  nerve,  in  frog,  141 
Vagotomy,  death  after  double,  279 
Vagus,  effect  of  stimulation  during  re- 
suscitation after  cerebral  ananiia, 
185 
in  mammals,  162,  20I 
inspiratory  and  expiratory  fibres  in. 

272 
negative  variation  of,  271 
nerve,  functir)ns  of,  goo 
of  frog,  dissection  of,  194 
relation  of,  to  respiration,  270 
Stimulation  o    in  dog, 210 
in  frog,  196 
in  man^mals,  162 
Valin.  354 

Valsalva's  experiment,  290 
Valves  of  veins,  82 

semilunar,  moment  of  closure.  96 
Varnishing  the  skin,  673 
Vaso-constrictor  and  vaso-dilator  nerves, 
differences  in  excitability  of,  173 
property  of  shod  blood.  45 
Vaso-dilator  fibren.  177 

in  cervical  sympathetic.  174 


Vaso-dilators  of  chord  1  tympani,  177 

of  nervi  erigenus,  177,  178 
Vaso-motor  centres.  iSo 

anatomical  relations  of,  183 
nature  of  t'>ne  of.  182 
spinal,  181 
nerves,  171,  173,  174 

cervical  sympathetic,  173 

course  of,  179 

in  splanchnic,  175 

in  trigeminus,  174 

of  brain,  174 

of  extremities,  175 

of  heart,  176 

of  lungs,  177 

of  muscle,  176 

of  veins.  178 

reflexes,  183,210,220 

studied      by     calormietric 
method,  186 
tone,  182 
Vaso-motors,  methods  of  investigating. 

172 
Veins,  action  of  adrenalin  on,  179 
circulation  in,  132 
factors  concerned  in  flow  in,  133 
measurement  of,  in  man,  133 
pressure  in,  132 
pulse  in,  131 

vaso-motor  nerves  of,  178 
velocity  of  blood  in,  134 
Vella's  fistula,  364 
Velocity  of  blood,  117,  127 
in  capillaries,  130 
in  veins,  134 
measurement  of,  120 
Vena  portae,  vaso-motor  nerves  of.  178 
Venous  blood,  tension  of  carbon  dioxide 
in,  260 
pressure -curve,  98 
pulse,  99,  131,  134 
tracing,  207 
Ventilation,  241 
N'eiitricle.  suction  action  of,  loj 
Ventricular  pressure -curve,  94 
Veratrine.  artion  of,  on  muscle,  728,787 
Vesicular  murmur,  230 
Vestibule,  paths  from,  899 
Vestibulo-spinal  tract,  839 

connections  of,  856 
Visceral  pain.  873 

Visero-psychic  area  of  Campbell,  93a 
Vision,  after-images.  1015 

apparent  size  of  cibjorts.  ioo3 
astigmatism,  1062 
blind  spot,  1004,  1064 
colour,  ion 
colour-blindness.  1019 
colour,  Hering's  theory,  1017 
mixing.  1068 
triangle.   1 014 
comparative  anatoniv,  973 


II32 


INDEX 


Vision,  contrast,  1016 

duration  of  stimuli,  1009 

experiments,  1058 

pick's  theory,  loio 

Holmgren's  wools,  1069 

irradiation,  102 1 

Listing's  law,  1023 

Maxwell's  spot,  1065 

measurement  field  vision,  1063 

ophthalmometer,  1062 

ophthalmoscope,  1065 

perimetry,  1018 

persistence  theory,  loio 

Purkinje's  figures,  1070 

relation  of  rods  and  cones  to,  1005 

skiascopy,  1066 

stereoscopic,  999 

Talbot's  law,  loio,  1070 

theory  of  identical  points,  997 

Young-Helmholtz  theory,  1013 
Visual  acuity,  1068 

centres,  931 

path,  894 

purple,  812,  1007 
Vital  capacity,  235,  297 
Vitamines,  619 
Vitreous  humour,  460 
Vivi-diffusion  apparatus,  48 
Vocal  cords,  301 

in  voice  production,  302 
movements  of,  in  respiration, 

305 
par^ysis  of,  310 
Voice,  301 

air-pressure  necessary  for,  303 
falsetto,  306 
in  children,  304 
nervous  mechanism  of,  309 
Voltaic  current,   alterations   in    excita- 
bilitv  and  conductivity  pro- 
duced by,  816 
stimulation  by,  783 
Volume  pulse,  127 
Voluntary  contraction,  734 


Volunta'y  contraction,  electrical  changes 
in,  736 
fatigue  in,  727 

movements,  acquisition  of,  945 
Vomiting,  328 

centre,  330 

induced  by  apomorphine,  329,  330 
Vowel  cavities,  308 

formation,  theories  of,  308 
Vowels  of  timbre,  307 

Warmth,  sensations  of,  1041 
Water,  absorption  of,  440 

in  diet,  617 

production  of,  in  the  body,  608 
Weber's  law  (stimuli),  1037 
Wernicke,  aphasia  of,  936 

zone  of,  936 
Wharton's  duct,  385 
Wheatstone's  bridge,  699 
Whey  protein,  348 
Word-blindness,  937 

-deafness,  933,  937 
Wounded  vessels,  sealing  of,  46 

Xanthin,  579,  582 

fever,  681 
Xantho-proteic  reaction,  8 
Xerostomia,  394 

Yawning,  282 

Yeast  and  vitamines,  620 

test  for  sugar,  518 
Yellow  atrophy,  acute,  and  excretion  of 
amino-acids,  576 

spot,  1064 
Young-Helmholtz  theory,  1013 

Zein,  as  a  food,  604 
Zone  of  Wernicke,  936 
Zoosterins,  360 
Zymase,  331 
Zymogen,  350 
granules,  370 


BaiUiere,  Tindall  <5r»  Cox,  8,  Henrietta  Street,  Cevent  Garden 


.;:W? 


